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Sample records for buprenorphine substitution treatment

  1. Diversion of methadone and buprenorphine from opioid substitution treatment: a staff perspective.

    PubMed

    Johnson, Björn; Richert, Torkel

    2014-01-01

    Opioid substitution treatment (OST) is still controversial, despite positive results. The issue of diversion to the illicit drug market is a cornerstone in the criticism typically voiced against the treatment. Little research is available concerning how professionals who work in OST view the issue of diversion. In this article, we discuss existing ideas and attitudes toward diversion of methadone and buprenorphine among OST staff in Sweden. The article is based on semi-structured interviews with 25 professionals working in eight OST-programs in southern Sweden. Diversion was seen as a deleterious phenomenon by the interviewees. Three problematic aspects were highlighted: medical risks in the form of overdose fatalities and the recruitment of new opiate/opioid users; negative consequences for the legitimacy of OST; and moral objections, since diversion means that the patients remain in a criminal environment. However, positive aspects were also highlighted. Illicit methadone or buprenorphine is perceived as safer than heroin. In this way, diversion can fulfill a positive function; for instance, if there is a shortage of access to regular treatment. Patients who share their medication with opioid-dependent friends are seen as less culpable than those who sell to anyone for money. PMID:25364995

  2. Methadone vs. buprenorphine/naloxone during early opioid substitution treatment: a naturalistic comparison of cognitive performance relative to healthy controls

    PubMed Central

    Rapeli, Pekka; Fabritius, Carola; Alho, Hannu; Salaspuro, Mikko; Wahlbeck, Kristian; Kalska, Hely

    2007-01-01

    Background Both methadone- and buprenorphine-treated opioid-dependent patients frequently show cognitive deficits in attention, working memory, and verbal memory. However, no study has compared these patient groups with each other during early opioid substitution treatment (OST). Therefore, we investigated attention, working memory, and verbal memory of opioid-dependent patients within six weeks after the introduction of OST in a naturalistic setting and compared to those of healthy controls. Methods The sample included 16 methadone-, 17 buprenorphine/naloxone-treated patients, and 17 healthy controls matched for sex and age. In both groups buprenorphine was the main opioid of abuse during the recent month. Benzodiazepine codependence, recent use, and comedication were also common in both patient groups. Analysis of variance was used to study the overall group effect in each cognitive test. Pair-wise group comparisons were made, when appropriate Results Methadone-treated patients, as a group, had significantly slower simple reaction time (RT) compared to buprenorphine/naloxone-treated patients. In Go/NoGo RT methadone patients were significantly slower than controls. Both patient groups were significantly debilitated compared to controls in working memory and verbal list learning. Only methadone patients were inferior to controls in story recall. In simple RT and delayed story recall buprenorphine/naloxone patients with current benzodiazepine medication (n = 13) were superior to methadone patients with current benzodiazepine medication (n = 13). When methadone patients were divided into two groups according to their mean dose, the patient group with a low dose (mean 40 mg, n = 8) showed significantly faster simple RT than the high dose group (mean 67 mg, n = 8). Conclusion Deficits in attention may only be present in methadone-treated early phase OST patients and may be dose-dependent. Working memory deficit is common in both patient groups. Verbal memory deficit

  3. Buprenorphine substitution treatment in France: drug users' views of the doctor-user relationship

    PubMed Central

    Guichard, Anne; Lert, France; Brodeur, Jean-Marc; Richard, Lucie

    2007-01-01

    The French system for drug substitution, or maintenance treatment, established in 1996, differs from the often strict conditions attached to methadone clinics in other countries. Because of the predominant role of general practitioners and the flexible prescription rules for Subutex® in France, the relationship between the physician and the drug user becomes a central element in the treatment. This article deals with the expectations that these users have of the physician, and their perception of his or her attitude towards them. In order to identify possible reasons for the absence of treatment compliance and of Subutex® misuse, it focuses on the users’ assessment of the physician’s response to the problems they report. This study, based on a diversified sample of 28 persons in treatment, showed 4 patterns of relationships between physicians and users, which differed in their focus: a) dosage, b) compliance, c) the person and d) obtaining a prescription. In all four case types, users had difficulty reporting other drug use or intravenous Subutex® injection within this relationship in which the stigma attached to drug dependence seems to reappear. Moreover, the lack of clarity about the treatment objectives and time frame limits the users’ ability to integrate the treatment into their lives and to commit themselves to it. The heterogeneity and fragility of the users’ situations are elements related to dependence that, during contact with the physician, require regular assessment of the individual’s situation and of the treatment objectives. This constant reappraisal of the situation with the physician should help to optimize the treatment and avoid the hiatus that can generate or continue “misuse.” PMID:17442473

  4. Opioid substitution treatment with sublingual buprenorphine in Manipur and Nagaland in Northeast India: what has been established needs to be continued and expanded

    PubMed Central

    Kumar, M Suresh; Natale, Richard D; Langkham, B; Sharma, Charan; Kabi, Rachel; Mortimore, Gordon

    2009-01-01

    Manipur and Nagaland in northeast India report an antenatal HIV prevalence of > 1% and the current HIV prevalence among injecting drug users is 24% and 4.5% respectively. Through support from DFID's Challenge Fund, Emmanuel Hospital Association (EHA) established thirteen drop-in-centres across the two states to deliver opioid substitution treatment with sublingual buprenorphine for 1200 injecting drug users. Within a short span of time the treatment has been found to be attractive to the clients and currently 1248 injecting opioid users are receiving opioid substitution treatment. The project is acceptable to the drug users, the families, the communities, religious as well as the militant groups. The treatment centres operate all days of the week, have trained staff members, utilize standardized protocols and ensure a strict supervised delivery system to prevent illicit diversion of buprenorphine. The drug users receiving the substitution treatment are referred to HIV voluntary counselling and testing. As this treatment has the potential to change HIV related risk behaviours, what has been established in the two states needs to be continued and expanded with the support from the Government of India. PMID:19243636

  5. Buprenorphine in the treatment of opiate dependence.

    PubMed

    Wesson, Donald R; Smith, David E

    2010-06-01

    Compelling clinical evidence establishes that buprenorphine is similar to methadone in efficacy for opiate detoxification and maintenance but safer than methadone in an overdose situation. The Drug Abuse Treatment Act of 2000 (DATA 2000) enabled US physicians with additional training to prescribe buprenorphine to a limited number of opiate-dependent patients. The sublingual tablets Subutex (buprenorphine alone) and Suboxone (a combination of buprenorphine and naloxone) meet the specifications of DATA 2000. Suboxone is intended to discourage intravenously administration and has less abuse potential than buprenorphine alone. Suboxone is generally recommended for maintenance treatment except for women who are pregnant. Subutex is recommended in treatment of pregnant women. A buprenorphine opiate withdrawal syndrome can occur in newborns. Although intravenous buprenorphine abuse is a significant public health problem in some countries, buprenorphine alone or in combination with naloxone has less potential for abuse than heroin and some prescription opiates, such as oxycodone. Pharmacotherapy from physicians' offices makes buprenorphine treatment acceptable to some opiate-dependent patients who would not accept treatment in traditional opiate-maintenance clinics. For reasons not adequately understood, some patients find discontinuation of buprenorphine following long-term use difficult. This article reviews the pharmacology of buprenorphine, summarizes evidence supporting the safety and efficacy of buprenorphine and provides clinical guidelines for treatment. PMID:20648912

  6. Factors affecting willingness to provide buprenorphine treatment

    PubMed Central

    Netherland, Julie; Botsko, Michael; Egan, James E.; Saxon, Andrew J.; Cunningham, Chinazo O.; Finkelstein, Ruth; Gourevitch, Mark N.; Renner, John A.; Sohler, Nancy; Sullivan, Lynn E.; Weiss, Linda; Fiellin, David A.

    2010-01-01

    Buprenorphine is an effective long-term opioid agonist treatment. As the only pharmacological treatment for opioid dependence readily available in office-based settings, buprenorphine may facilitate a historic shift in addiction treatment from treatment facilities to general medical practices. Although many patients have benefited from the availability of buprenorphine in the United States, almost half of current prescribers are addiction specialists suggesting that buprenorphine treatment has not yet fully penetrated general practice settings. We examined factors affecting willingness to offer buprenorphine treatment among physicians with different levels of prescribing experience. Based on their prescribing practices, physicians were classified as experienced, novice, or as a nonprescriber and asked to assess the extent to which a list of factors impacted their prescription of buprenorphine. Several factors affected willingness to prescribe buprenorphine for all physicians: staff training; access to counseling and alternate treatment; visit time; buprenorphine availability; and pain medications concerns. Compared with other physicians, experienced prescribers were less concerned about induction logistics and access to expert consultation, clinical guidelines, and mental health services. They were more concerned with reimbursement. These data provide important insight into physician concerns about buprenorphine and have implications for practice, education, and policy change that may effectively support widespread adoption of buprenorphine. PMID:18715741

  7. Buprenorphine

    PubMed Central

    Kahan, Meldon; Srivastava, Anita; Ordean, Alice; Cirone, Sharon

    2011-01-01

    Abstract Objective To review the use of buprenorphine for opioid-addicted patients in primary care. Quality of evidence The MEDLINE database was searched for literature on buprenorphine from 1980 to 2009. Controlled trials, meta-analyses, and large observational studies were reviewed. Main message Buprenorphine is a partial opioid agonist that relieves opioid withdrawal symptoms and cravings for 24 hours or longer. Buprenorphine has a much lower risk of overdose than methadone and is preferred for patients at high risk of methadone toxicity, those who might need shorter-term maintenance therapy, and those with limited access to methadone treatment. The initial dose should be given only after the patient is in withdrawal. The therapeutic dose range for most patients is 8 to 16 mg daily. It should be dispensed daily by the pharmacist with gradual introduction of take-home doses. Take-home doses should be introduced more slowly for patients at higher risk of abuse and diversion (eg, injection drug users). Patients who fail buprenorphine treatment should be referred for methadone- or abstinence-based treatment. Conclusion Buprenorphine is an effective treatment of opioid addiction and can be safely prescribed by primary care physicians. PMID:21402963

  8. Buprenorphine

    PubMed Central

    Valadez-Meltzer, Adela

    2005-01-01

    Opioid dependence is a significant and growing problem in the United States. For nearly a century, federal regulations have made it illegal for psychiatrists and other physicians to pharmacologically manage this condition in an office-based setting using opioids. The passage of the Drug Addiction Treatment Act of 2000 has made it possible for all physicians to prescribe buprenorphine to patients in such a setting. Buprenorphine, a partial mu-opoid receptor agonist, has unique pharmacologic properties that distinguish it from methadone and other medications used in the treatment of opioid dependence. It has been shown to be as effective as methadone and is generally safe and well-tolerated. It is available in two sublingual formulations: Subutex, which contains only buprenorphine, and Suboxone, which also contains naloxone. Physicians who wish to prescribe either must obtain a special waiver from the federal government and are currently limited to prescribing it for 30 patients at a time. PMID:21124750

  9. Buprenorphine Treatment for Probationers and Parolees

    PubMed Central

    Gordon, Michael S.; Kinlock, Timothy W.; Schwartz, Robert P.; Couvillion, Kathryn A.; Sudec, Laura J.; O’Grady, Kevin E.; Vocci, Frank J.; Shabazz, Hamin

    2014-01-01

    Background Pharmacotherapy studies involving buprenorphine have rarely been conducted with US community corrections populations. This is one of the first reports of buprenorphine treatment outcomes of adult opioid-dependent probationers and parolees. Methods This longitudinal study examined the 3-month treatment outcomes for a sample of probation and parole clients (N=64) who received community-based buprenorphine treatment. Results Approximately two-thirds of the sample (67%) were still in treatment at three months post-baseline. Furthermore, there was a significant decline in the number of self-reported heroin use days and crime days from baseline to three months post-baseline. While there was not a significant reduction in reincarcerations, there was no evidence that they had increased. Conclusions Given that buprenorphine is approved by the FDA as a safe, effective treatment for opioid use disorders, individuals on parole or probation should have the opportunity to benefit from it through community-based programs. PMID:24701967

  10. Diversion of methadone and buprenorphine from opioid substitution treatment: patients who regularly sell or share their medication.

    PubMed

    Johnson, Björn; Richert, Torkel

    2015-01-01

    Diversion-the practice of patients selling or sharing their medication-is a much debated problem of opioid substitution treatment. Regular diversion by patients was studied at 11 opioid substitution treatment programs in the south of Sweden. Using quantitative and qualitative data, it was investigated whether those patients differ from other patients, their motives for and means of diversion, and who the recipients are. Regular diverters are a small, yet heterogeneous group. Continued illicit drug use, however, stands out as a common risk factor. Pecuniary need and a desire to help friends are other important motives. The client base mainly consists of people from the regular diverters' own drug milieus. PMID:25496247

  11. Community Treatment Programs Take Up Buprenorphine

    PubMed Central

    Casadonte, Paul P.; Kolodner, George F.; Horton, Terry; McMurphy, Suzanne M.

    2004-01-01

    Clinicians have been working out ways to incorporate buprenorphine into their treatment models. Representatives of three addiction treatment programs—a Veterans Affairs methadone clinic, a group of outpatient mental health centers, and a nationwide organization of therapeutic communities—talk about their plans and experiences. PMID:18552729

  12. Buprenorphine treatment for narcotic addiction: not without risks.

    PubMed

    Sansone, Randy A; Sansone, Lori A

    2015-01-01

    While most clinicians will never prescribe buprenorphine or combined buprenorphine/naloxone, familiarity with the risks of these pharmacological approaches to the treatment of narcotic addiction remains relevant. Overall, medication-assisted treatment has clearly resulted in meaningful gains for a number of individuals who are addicted to narcotics (i.e., opiates and opioids). However, a certain level of risk is inherent with these approaches. For example, both buprenorphine and buprenorphine/naloxone may be diverted and misused (e.g., intravenously injected, intranasally administered), particularly buprenorphine. Likewise, when illicitly injected, both can cause infectious complications as well as result in death from overdose. The risk of death with buprenorphine overdose appears to be heightened with the coadministration of either benzodiazepines or sedative/hypnotics. To conclude, as with all interventions in medicine, buprenorphine treatment for narcotic addiction has a clinically fluctuating risk/benefit equation that must be continually monitored. PMID:25973324

  13. Buprenorphine Treatment for Narcotic Addiction: Not Without Risks

    PubMed Central

    Sansone, Lori A.

    2015-01-01

    While most clinicians will never prescribe buprenorphine or combined buprenorphine/naloxone, familiarity with the risks of these pharmacological approaches to the treatment of narcotic addiction remains relevant. Overall, medication-assisted treatment has clearly resulted in meaningful gains for a number of individuals who are addicted to narcotics (i.e., opiates and opioids). However, a certain level of risk is inherent with these approaches. For example, both buprenorphine and buprenorphine/naloxone may be diverted and misused (e.g., intravenously injected, intranasally administered), particularly buprenorphine. Likewise, when illicitly injected, both can cause infectious complications as well as result in death from overdose. The risk of death with buprenorphine overdose appears to be heightened with the coadministration of either benzodiazepines or sedative/hypnotics. To conclude, as with all interventions in medicine, buprenorphine treatment for narcotic addiction has a clinically fluctuating risk/benefit equation that must be continually monitored. PMID:25973324

  14. Medication-assisted treatment for opioid addiction: methadone and buprenorphine.

    PubMed

    Saxon, Andrew J; Hser, Yih-Ing; Woody, George; Ling, Walter

    2013-12-01

    Among agents for treatment of opioid addiction, methadone is a full mu-opioid receptor agonist, whereas buprenorphine is a partial agonist. Both are long-acting. Buprenorphine has a superior safety profile. Methadone is formulated for oral administration and buprenorphine for sublingual administration. A subdermal buprenorphine implant with a 6-month duration of action is being considered for approval by the U.S. Food and Drug Administration. Both medications reduce mortality rates and improve other outcomes. Data from a recent randomized controlled comparison of both medications (N = 1269) show better treatment retention with methadone but reduced illicit opioid use early in treatment with buprenorphine. Human immunodeficiency virus (HIV) risk behaviors were measured using the Risk Behavior Survey at baseline, 12 weeks, and 24 weeks for study completers. In the 30 days prior to treatment entry, 14.4% of the completers randomized to treatment with buprenorphine (n = 340) and 14.1% of the completers randomized to methadone treatment (n = 391) shared needles. The percent sharing needles decreased to 2.4% for buprenorphine and 4.8 for methadone in the 30 days prior to Week 24 (p < 0.0001). In the 30 days prior to treatment entry, 6.8% of the completers randomized to buprenorphine and 8.2% of the completers randomized to methadone had multiple sexual partners, with only 5.2% and 5.1%, respectively, reporting multiple partners at Week 24 (p < 0.04). PMID:24436573

  15. Urine naloxone concentration at different phases of buprenorphine maintenance treatment.

    PubMed

    Heikman, Pertti; Häkkinen, Margareeta; Gergov, Merja; Ojanperä, Ilkka

    2014-03-01

    In spite of the benefits of buprenorphine-naloxone co-formulation (BNX) in opioid maintenance treatment, the naloxone component has not prevented parenteral use of BNX. Current laboratory methods are not sufficient to differentiate between therapeutic and illicit use of buprenorphine, and little is known about urine naloxone concentrations. Measurement of urine naloxone, together with buprenorphine and norbuprenorphine, might help to determine the naloxone source and administration route. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for this purpose. Naloxone, buprenorphine, and norbuprenorphine total concentrations were measured in urine samples from opioid-dependent patients before and during stable and unstable phases of maintenance treatment with BNX. The limit of quantification in urine was 1.0 µg/L for naloxone, buprenorphine and norbuprenorphine. Before treatment, all samples contained buprenorphine but the median naloxone concentration was 0 µg/L. During the maintenance treatment with BNX all urine samples were positive for naloxone, buprenorphine and norbuprenorphine. The naloxone concentration at a stable phase of treatment (median 60 µg/L, range 5-200 µg/L) was not different from the naloxone concentration at an unstable phase (70 µg/L, 10-1700 µg/L). Applying an upper limit of 200 µg/L to the sample, the median naloxone/buprenorphine ratio was higher in the high than in the low naloxone concentration group (0.9 vs 0.3, respectively). This study suggests that naloxone in urine can act as an indicator of compliance with BNX. Parenteral use of BNX was associated with a high naloxone/buprenorphine ratio. Negative naloxone with positive buprenorphine suggests the use/abuse of buprenorphine alone. PMID:23512803

  16. Comparison of Buprenorphine Treatment for Opioid Dependence in Three Settings

    PubMed Central

    Hillhouse, Maureen; Donovick, Roger; Cunningham-Rathner, Jerry; Charuvastra, Charlie; Torrington, Matthew; Esagoff, Asher E.; Ling, Walter

    2011-01-01

    Although use of buprenorphine in the treatment of opioid dependence is expected to continue to increase, little is known about the optimal setting for providing the medical and psychosocial care required with buprenorphine pharmacotherapy. OBJECTIVE This study compared buprenorphine therapy delivered in three distinct treatment settings: an opioid-treatment program (OTP) offering individual counseling; a group counseling program utilizing the manualized Matrix Model (MMM) of cognitive-behavioral treatment; and a private clinic setting mirroring standard medical management for buprenorphine treatment provided specifically at a psychiatrist’s private practice (PCS). METHOD Participants were inducted on buprenorphine and provided with treatment over a 52-week study duration. All participants were scheduled for weekly treatment visits for the first 6 study weeks, and two sites reduced treatment to monthly visits for dispensing of medication and psychosocial counseling. Outcomes include opioid use, participant retention in treatment, and treatment participation. RESULTS Participants presenting for treatment at the sites differed only by race/ethnicity, and opioid use did not differ by site. Retention differed by treatment site, with the number of participants who stayed in the study until the end of 20 weeks significantly associated with treatment site. The mean number of minutes spent in each individual counseling session also differed by site. Although no difference in opioid use by treatment site was found, results document a significant association between opioid use and buprenorphine dose. DISCUSSION These results show some differences by treatment site, although the similarity and relative ease in which the sites were able to recruit participants for treatment with buprenorphine, and minor implementation problems reported suggests the feasibility of treatment with buprenorphine across various treatment settings. CONCLUSION Similar rates of continued opioid use

  17. Retention in methadone and buprenorphine treatment among African Americans

    PubMed Central

    Gryczynski, Jan; Mitchell, Shannon Gwin; Jaffe, Jerome H.; Kelly, Sharon M.; Myers, C. Patrick; O’Grady, Kevin E.; Olsen, Yngvild K.; Schwartz, Robert P.

    2013-01-01

    Methadone has been the most commonly used pharmacotherapy for the treatment of opioid dependence in U.S. public sector treatment, but availability of buprenorphine as an alternative medication continues to increase. Drawing data from two community-based clinical trials that were conducted nearly contemporaneously, this study examined retention in methadone vs. buprenorphine treatment over 6 months among urban African Americans receiving treatment in one of four publicly-funded programs (N= 478; 178 methadone; 300 buprenorphine). Adjusting for confounds related to medication selection, survival analysis revealed that buprenorphine patients are at substantially higher risk of dropout compared to methadone patients (HR= 2.43; p< .001). Buprenorphine’s retention disadvantage appears to be concentrated in the earlier phases of treatment (approximately the first 50 days), after which risk of subsequent dropout becomes similar for the two medications. These findings confirm a retention disparity between methadone and buprenorphine in this population, and suggest potential avenues for future research to enhance retention in buprenorphine treatment. PMID:23566446

  18. Leaving Buprenorphine Treatment: Patients’ Reasons for Cessation of Care

    PubMed Central

    Gryczynski, Jan; Mitchell, Shannon Gwin; Jaffe, Jerome H.; O’Grady, Kevin E.; Olsen, Yngvild K.; Schwartz, Robert P.

    2013-01-01

    Many opioid-dependent patients leave treatment prematurely. This study is a planned secondary analysis from a randomized trial of counseling for African Americans (N=297) entering buprenorphine treatment at one of two outpatient programs. This study examines: (1) whether patients’ initial treatment duration intentions prospectively predict retention; and (2) patients’ reasons for leaving treatment. Participants were queried about their treatment duration intentions at treatment entry, and their reasons for leaving treatment at 6-month follow-up. At baseline, 28.0% reported wanting to stay in buprenorphine treatment less than 6 months, while 42.1% actually left buprenorphine treatment within 6 months. However, participants intending short-term buprenorphine at the outset were not at elevated risk of early treatment discontinuation (OR=1.15; p=.65). Participants attributed treatment cessation predominantly to conflicts with staff, involuntary discharge, and perceived inflexibility of the program. Future research should examine patient-centered models of buprenorphine treatment that could improve retention. PMID:24238714

  19. Buprenorphine-based regimens and methadone for the medical management of opioid dependence: selecting the appropriate drug for treatment.

    PubMed

    Maremmani, Icro; Gerra, Gilberto

    2010-01-01

    Maintenance therapy with methadone or buprenorphine-based regimens reduces opioid dependence and associated harms. The perception that methadone is more effective than buprenorphine for maintenance treatment has been based on low buprenorphine doses and excessively slow induction regimens used in early buprenorphine trials. Subsequent studies show that the efficacy of buprenorphine sublingual tablet (Subutex®) or buprenorphine/naloxone sublingual tablet (Suboxone®) is equivalent to that of methadone when sufficient buprenorphine doses, rapid induction, and flexible dosing are used. Although methadone remains an essential maintenance therapy option, buprenorphine-based regimens increase access to care and provide safer, more appropriate treatment than methadone for some patients. PMID:20958853

  20. Naltrexone and buprenorphine combination in the treatment of opioid dependence.

    PubMed

    Gerra, G; Fantoma, A; Zaimovic, A

    2006-11-01

    Naltrexone treatment has demonstrated some advantages for special populations of heroin addicted individuals, but patients' compliance seems to be very poor, with a low adherence and low retention rate. Kappa-opioid system overdrive seems to contribute to opioid protracted abstinence syndrome, with dysphoria and psychosomatic symptoms during naltrexone treatment. The objective of this observational study was to determine the effectiveness of a functional k antagonist in improving naltrexone treatment outcome. A partial mu agonist/kappa antagonist (buprenorphine) and a mu antagonist (naltrexone) were combined during a 12 weeks protocol, theoretically leaving k antagonism as the major medication effect. Sixty patients were submitted to outpatient rapid detoxification utilizing buprenorphine and opioid antagonists. Starting on the fifth day, 30 patients (group A) received naltrexone alone. Alternatively, 30 patients (group B) received naltrexone (50mg oral dose) plus buprenorphine (4 mg sublingual) for the 12 weeks of the observational study. The endpoints of the study were: retention in treatment, negative urinalyses, changes in psychological symptoms (Symptom Checklist-90 Revised: SCL-90) and craving scores (visual analysis scale (VAS)). Thirty-four subjects (56.67%) completed the 12 weeks study. Twenty-one patients (35.0%) had all urine samples negative for opiates and cocaine. nine subjects (15.0%) had urine samples negative for cocaine and opiates for the last 4 weeks of the study. five subjects (8.3%) continued to use cocaine during the 12 weeks of the study. No significant change in pupillary diameter after buprenorphine administration was evidenced during clinical observations from baseline across the weekly measurements. Retention rates in group A (naltrexone) and group B (naltrexone + buprenorphine) at week 12 were respectively 40% (12 patients) and 73.33% (22 patients), with a significant difference in favour of group B (p= 0.018). Patients treated with

  1. Buprenorphine Prescribing Availability in a Sample of Ohio Specialty Treatment Organizations

    PubMed Central

    Molfenter, Todd; Sherbeck, Carol; Zehner, Mark; Starr, Sandy

    2015-01-01

    Objective Buprenorphine, a medication for treating opioid dependence, is underutilized in specialty addiction treatment organizations. Only physicians who have obtained a buprenorphine prescribing license or “waiver” may administer this medication. A limited number of physicians are pursuing this waiver, and a concern in the substance use disorder treatment field is that the shortage of prescribers could be contributing to the low use of buprenorphine at specialty addiction treatment centers. The objective of this study is to assess Ohio specialty treatment organizations’ access to buprenorphine prescribers and the barriers they encounter when seeking new physician prescribing capacity. Methods Forty-one Ohio specialty addiction treatment organizations were invited to complete a survey of their buprenorphine practices and availability of buprenorphine prescribers during August–October 2014. Data was collected on pharmacotherapies used in the treatment of opioid dependence, arrangements treatment organizations have with prescribing physicians, buprenorphine prescribing capacity, and barriers encountered in recruiting new physician prescribers. Results Thirty-seven treatment organizations responded, for a response rate of 90.2%. Seventy-eight percent (n=29) of the sample provided buprenorphine therapy. Of those treatment organizations, 48.3% (n=14) reported insufficient prescribing capacity. Of those, 50% (n=7) indicated they had to turn patients away from buprenorphine therapy due to limited physician prescribing capacity. Conclusion The study suggests that buprenorphine use is constrained by limited physician prescribing capacity, to the degree that 24.1% of the organizations surveyed using buprenorphine therapy had to turn patients away. Potential remedies include encouraging more specialty treatment organizations to have physicians on staff, removing the Drug Addiction Treatment Act (DATA 2000) cap that limits physician buprenorphine caseloads at 100

  2. Patterns of non-compliant buprenorphine, levomethadone, and methadone use among opioid dependent persons in treatment

    PubMed Central

    2014-01-01

    Background The non-compliant use of opioid substitution treatment (OST) medicines is widespread and well-documented. However, less is known about characteristics of non-compliant OST medicine use and the factors that predict it. The two main goals of this study are to compare characteristics of non-compliant levomethadone, methadone, and buprenorphine use and to explore factors that may differentially predict it among opioid dependent persons in treatment. Methods Data from 595 opioid dependent patients with non-compliant OST medicine use were analyzed. Characteristics of use between substances were compared using chi-squared tests and predictive factors were explored through multinomial logistic regressions. Results Non-compliant levomethadone and methadone use was characterized by more frequent parallel consumption of other psychoactive substances and intravenous use, whereas buprenorphine was more often procured without a prescription. Regarding predictive factors, methadone was perceived to relieve withdrawal symptoms better than buprenorphine and levomethadone was perceived as being better at modulating the effects of other substances and worst at enhancing mood. Conclusions Patterns of non-compliant use differ according to OST medicine. These patterns are considered with the reduction of non-compliant use and the improvement of treatment in mind. PMID:24885218

  3. Parenting and Concerns of Pregnant Women in Buprenorphine Treatment

    PubMed Central

    Rizzo, Rachel A; Neumann, Anne M; King, Stella OC; Hoey, Robert F; Finnell, Deborah S; Blondell, Richard D

    2014-01-01

    Purpose Opioid-dependent pregnant women are characterized by drug use during pregnancy and deficits in knowledge of newborn care and feeding, and of child development. We assessed parenting skills and concerns among pregnant women in buprenorphine treatment for prescription opioid-dependence. Study Design and Methods We interviewed 32 pregnant women who received buprenorphine treatment for prescription opioid dependence in a primary care setting and administered questionnaires, including the Adult-Adolescent Parenting Inventory version 2 (AAPI-2) and Childhood Experience of Care and Abuse Questionnaire. Results AAPI-2 scores revealed medium risk of abuse for all five scales: inappropriate expectations of the child, low level of empathy, strong belief in corporal punishment, reversal of parent-child roles, and oppression of children’s power and independence. Primary concerns of participants were neonatal abstinence syndrome (NAS) and their child’s health. Pregnant women who received buprenorphine for treatment of prescription opioid dependence showed a lack of appropriate parenting skills, but did not express concern about their ability to parent. Clinical Implications Our findings suggest need for nurses to assist prescription opioid-dependent pregnant women in acquiring additional parenting skills, to refer for educational parenting intervention, and to educate patients about NAS. PMID:25137081

  4. Sublingual Buprenorphine for Treatment of the Neonatal Abstinence Syndrome: A Randomized Trial

    PubMed Central

    Kraft, Walter K.; Gibson, Eric; Dysart, Kevin; Damle, Vidula S.; LaRusso, Jennifer L.; Greenspan, Jay S.; Moody, David E.; Kaltenbach, Karol; Ehrlich, Michelle E.

    2008-01-01

    Objective In utero exposure to drugs of abuse can lead to the Neonatal Abstinence Syndrome (NAS), a condition that is associated with prolonged hospitalization. Buprenorphine is a partial mu opioid agonist used for treatment of adult detoxification and maintenance, but has never been administered to neonates with opioid abstinence. The primary objective of this study was to demonstrate the feasibility and to the extent possible in this sized study, the safety of sublingual buprenorphine in the treatment of NAS. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered. Methods We conducted a randomized, open-label, active control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to sublingual buprenorphine 13.2–39 mcg/kg/day administered in three divided doses and thirteen to standard of care oral neonatal opium solution (NOS). Dose decisions were made using a modified Finnegan scoring system. Results Sublingual buprenorphine was largely effective in controlling NAS. Greater than 98% of plasma concentrations ranged from undetectable to approximately 0.60 ng/ml, which is less than needed to control abstinence symptoms in adults. The ratio of buprenorphine to norbuprenorphine was larger than that seen in adults, suggesting a relative impairment of N-dealkylation. Three infants receiving buprenorphine and one infant receiving standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for the NOS group was 32 compared to 22 days for the buprenorphine group. The mean length of stay for the NOS group was 38 days compared to 27 days for the buprenorphine group. Treatment with buprenorphine was well tolerated. Conclusions Buprenorphine administered via the sublingual route is feasible and apparently safe, and may represent a novel treatment

  5. Optimizing psychosocial support during office-based buprenorphine treatment in primary care: patients’ experiences and preferences

    PubMed Central

    Fox, Aaron D.; Masyukova, Mariya; Cunningham, Chinazo O.

    2015-01-01

    Background Buprenorphine maintenance treatment is effective and has been successfully integrated into HIV and primary care settings. However, one key barrier to providers prescribing buprenorphine is their perception that they are unable to provide adequate counseling or psychosocial support to patients with opioid addiction. This qualitative study investigated supportive elements of office-based buprenorphine treatment that patients perceived to be most valuable. Methods We conducted five focus groups with 33 buprenorphine treatment-experienced participants. Focus groups were audio-recorded and transcribed. Iterative readings of transcripts and grounded theory analysis revealed common themes. Results Overall, participants perceived that buprenorphine treatment helped them to achieve their treatment goals and valued the flexibility, accessibility, and privacy of treatment. Participants identified interpersonal and structural elements of buprenorphine treatment that provided psychosocial support. Participants desired good physician-patient relationships, but also valued care delivery models that were patient-centered, created a safe place for self-disclosure, and utilized coordinated team-based care. Conclusions Participants derived psychosocial support from their prescribing physician, but were also open to collaborative or team-based models of care, as long as they were voluntary and confidential. Buprenorphine prescribing physicians without access to referral options for psychosocial counseling could focus on maintaining non-judgmental attitudes and shared decision making during patient encounters. Adding structure and psychosocial support to buprenorphine treatment through coordinated team-based care also seems to have great promise. PMID:26566712

  6. Bringing Buprenorphine-Naloxone Detoxification to Community Treatment Providers: The NIDA Clinical Trials Network Field Experience

    PubMed Central

    Amass, Leslie; Ling, Walter; Freese, Thomas E.; Reiber, Chris; Annon, Jeffrey J.; Cohen, Allan J.; M.F.T.; McCarty, Dennis; Reid, Malcolm S.; Brown, Lawrence S.; Clark, Cynthia; Ziedonis, Douglas M.; Krejci, Jonathan; Stine, Susan; Winhusen, Theresa; Brigham, Greg; Babcock, Dean; L.C.S.W.; Muir, Joan A.; Buchan, Betty J.; Horton, Terry

    2005-01-01

    In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone (Suboxone®) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Trials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provided an unprecedented field test of its use in twelve diverse community-based treatment programs. Opioid-dependent men and women were randomized to a thirteen-day buprenorphine-naloxone taper regimen for short-term opioid detoxification. The 234 buprenorphine-naloxone patients averaged 37 years old and used mostly intravenous heroin. Direct and rapid induction onto buprenorphine-naloxone was safe and well tolerated. Most patients (83%) received 8 mg buprenorphine-2 mg naloxone on the first day and 90% successfully completed induction and reached a target dose of 16mg buprenorphine-4 mg naloxone in three days. Medication compliance and treatment engagement was high. An average of 81% of available doses was ingested, and 68% of patients completed the detoxification. Most (80.3%) patients received some ancillary medications with an average of 2.3 withdrawal symptoms treated. The safety profile of buprenorphine-naloxone was excellent. Of eighteen serious adverse events reported, only one was possibly related to buprenorphine-naloxone. All providers successfully integrated buprenorphine-naloxone into their existing treatment milieus. Overall, data from the CTN field experience suggest that buprenorphine-naloxone is practical and safe for use in diverse community treatment settings, including those with minimal experience providing opioid-based pharmacotherapy and/or medical detoxification for opioid dependence. PMID:15204675

  7. Economic and social effects of high-dose buprenorphine substitution therapy. Six-month results.

    PubMed

    Lavignasse, Pierre; Lowenstein, William; Batel, Philippe; Constant, Marie-Véronique; Jourdain, Jean-Jacques; Kopp, Pierre; Reynaud-Maurupt, Catherine; Riff, Bertrand; Videau, Benjamin; Mucchielli, Alain

    2002-05-01

    The purpose of this study was to analyze the impact of high-dose buprenorphine substitution therapy in opiate-dependent patients in terms of use of psychoactive substances, associated risks, social integration, and the social cost generated by the use of these substances. This was a longitudinal quantitative survey carried out in 1083 patients who were evaluated at three times: at the beginning of substitution therapy (D0), at 6 months and then at 12 months follow up (M6, M12). Data were collected with an anonymous self-administered questionnaire, completed in the presence of an investigating physician. Results demonstrated that patients treated with high-dose buprenorphine for 6 months, consumed fewer psychoactive drugs (heroin, cocaine, benzodiazepines) and had fewer associated risks. Additionally, several criteria involved in social integration showed improvement; morbidity and mortality decreased after the first 6 months of substitution therapy. These improvements were followed by a reduction in the social cost of drug use generated by the group of patients considered. These initial results require confirmation in the final analysis of the study taking into account the 12-month follow up. PMID:12218879

  8. Prior Experience with Non-Prescribed Buprenorphine: Role in Treatment Entry and Retention.

    PubMed

    Monico, Laura B; Mitchell, Shannon Gwin; Gryczynski, Jan; Schwartz, Robert P; O'Grady, Kevin E; Olsen, Yngvild K; Jaffe, Jerome H

    2015-10-01

    Buprenorphine availability continues to expand as an effective treatment for opioid dependence, but increases in availability have also been accompanied by increases in non-prescribed use of the medication. Utilizing data from a randomized clinical trial, this mixed-method study examines associations between use of non-prescribed buprenorphine and subsequent treatment entry and retention. Quantitative analyses (N = 300 African American buprenorphine patients) found that patients with prior use of non-prescribed buprenorphine had significantly higher odds of remaining in treatment through 6 months than patients who were naïve to the medication upon treatment entry. Qualitative data, collected from a subsample of participants (n = 20), identified three thematic explanations for this phenomenon: 1) perceived effectiveness of the medication; 2) cost of obtaining prescription buprenorphine compared to purchasing non-prescribed medication; and 3) convenience of obtaining the medication via daily-dosing or by prescription compared to non-prescribed buprenorphine. These findings suggest a dynamic relationship between non-prescribed buprenorphine use and treatment that indicates potential directions for future research into positive and negative consequences of buprenorphine diversion. PMID:25980599

  9. Buprenorphine Treatment of Opioid-Dependent Pregnant Women: A Comprehensive Review

    PubMed Central

    Jones, Hendrée E.; Arria, Amelia M.; Baewert, Andjela; Heil, Sarah H.; Kaltenbach, Karol; Martin, Peter R.; Coyle, Mara G.; Selby, Peter; Stine, Susan M.; Fischer, Gabriele

    2015-01-01

    Aims This paper reviews the published literature regarding outcomes following maternal treatment with buprenorphine in five areas: maternal efficacy, fetal effects, neonatal effects, effects on breast milk, and longer-term developmental effects. Methods Within each outcome area, findings are summarized first for the 3 randomized controlled trials and then for the 44 non-randomized studies (i.e., prospective studies, case reports and series, and retrospective chart reviews), only 28 of which involve independent samples. Results Results indicate that maternal treatment with buprenorphine has comparable efficacy to methadone, although difficulties may exist with current buprenorphine induction methods. The available fetal data suggest buprenorphine results in less physiologic suppression of fetal heart rate and movements than methadone. Regarding neonatal effects, perhaps the single definitive conclusion is that prenatal buprenorphine treatment results in a clinically significant less severe neonatal abstinence syndrome (NAS) than treatment with methadone. The limited research suggests that, like methadone, buprenorphine is compatible with breastfeeding. Data available thus far suggest that there are no deleterious effects of in utero buprenorphine exposure on infant development. Conclusions Buprenorphine produces a less severe neonatal abstinence syndrome than methadone, but there is still a role for methadone in the treatment of opioid dependence during pregnancy. PMID:23106923

  10. Text message content preferences to improve buprenorphine maintenance treatment in primary care.

    PubMed

    Tofighi, Babak; Grossman, Ellie; Bereket, Sewit; D Lee, Joshua

    2016-01-01

    Few studies have evaluated text message content preferences to support evidence-based treatment approaches for opioid use disorders, and none in primary care office-based buprenorphine treatment settings. This study assessed the acceptability and preferences for a tailored text message intervention in support of core office-based buprenorphine treatment medical management components (e.g., treatment adherence, encouraging abstinence, 12-step group participation, motivational interviewing, and patient-provider communication as needed). There were 97 patients enrolled in a safety net office-based buprenorphine treatment program who completed a 24-item survey instrument that consisted of multiple-choice responses, 7-point Likert-type scales, binomial "Yes/No" questions, and open-ended responses. The sample was predominately male (81%), had an average age of 46 years, and was diverse (64% ethnic/racial minorities); 56% lacked stable employment. Respondents were interested in receiving text message appointment reminders (90%), information pertaining to their buprenorphine treatment (76%), supportive content (70%), and messages to reduce the risk of relapse (88%). Participants preferred to receive relapse prevention text messages during all phases of treatment: immediately after induction into buprenorphine treatment (81%), a "few months" into treatment (57%), and after discontinuing buprenorphine treatment (72%). Respondents also expressed interest in text message content enhancing self-efficacy, social support, and frequent provider communication to facilitate unobserved "home" induction with buprenorphine. Older participants were significantly less receptive to receiving text message appointment reminders; however, they were as interested in receiving supportive, informational, and relapse prevention components compared to younger respondents. Implications for integrating a text message support system in office-based buprenorphine treatment are discussed. PMID

  11. Impact of Research Network Participation on the Adoption of Buprenorphine for Substance Abuse Treatment

    PubMed Central

    Rieckmann, Traci R.; Abraham, Amanda J.; Kovas, Anne E.; McFarland, Bentson H.; Roman, Paul M.

    2014-01-01

    There is a growing body of research supporting the use of buprenorphine and other medication assisted treatments (MATs) for the rapidly accelerating opioid epidemic in the United States. Despite numerous advantages of buprenorphine (accessible in primary care, no daily dosing required, minimal stigma), implementation has been slow. As the field progresses, there is a need to understand the impact of participation in practitioner-scientist research networks on acceptance and uptake of buprenorphine. This paper examines the impact of research network participation on counselor attitudes toward buprenorphine addressing both counselor-level characteristics and program-level variables using hierarchical linear modeling (HLM) to account for nesting of counselors within treatment programs. Using data from the National Treatment Center Study, this project compares privately funded treatment programs (n=345) versus programs affiliated with the National Institute on Drug Abuse Clinical Trials Network (CTN) (n=198). Models included 922 counselors in 172 CTN programs and 1,203 counselors in 251 private programs. Results of two-level HLM logistic (Bernoulli) models revealed that counselors with higher levels of education, larger caseloads, more buprenorphine-specific training, and less preference for 12-step treatment models were more likely to perceive buprenorphine as acceptable and effective. Furthermore, buprenorphine was 50% more likely to be perceived as effective among counselors working in CTN-affiliated programs as compared to private programs. This study suggests that research network affiliation positively impacts counselors’ acceptance and perceptions of buprenorphine. Thus, research network participation can be utilized as a means to promote positive attitudes toward the implementation of innovations including medication assisted treatment. PMID:24594902

  12. African American Patients Seeking Treatment in the Public Sector: Characteristics of Buprenorphine v. Methadone Patients

    PubMed Central

    Mitchell, Shannon Gwin; Kelly, Sharon M.; Gryczynski, Jan; Myers, C. Patrick; Jaffe, Jerome H.; O’Grady, Kevin E.; Olsen, Yngvild K.; Schwartz, Robert P.

    2011-01-01

    Background To expand its public-sector treatment capacity, Baltimore City made buprenorphine treatment accessible to low-income, largely African American residents. This study compares the characteristics of patients entering methadone treatment v. buprenorphine treatment to determine whether BT was attracting different types of patients. Methods Participants consisted of two samples of adult heroin-dependent African Americans. The first sample was newly-admitted to a health center or a mental health center providing buprenorphine (N=200), and the second sample was newly-admitted to one of two hospital-based methadone programs (N=178). The Addiction Severity Index (ASI) and the Friends Supplemental Questionnaire were administered at treatment entry and data were analyzed with logistic regression. Results BT participants were more likely to be female (p=.017) and less likely to inject (p=.001). Participants with only prior buprenorphine treatment experience were nearly five time more likely to enter buprenorphine than methadone treatment (p<.001). Those with experience with both treatments were more than twice as likely to enter BT (OR=2.7, 95% CI=1.11–6.62; p=.028). In the 30 days prior to treatment entry, BT participants reported more days of medical problems (p=.002) and depression (p=.044), and were more likely to endorse a lifetime history of depression (p<.001). Conclusion Methadone and buprenorphine treatment provided in the public sector may attract different patient subpopulations. Providing buprenorphine treatment through drug treatment programs co-located with a health and mental health center may have accounted for their higher rates of medical and psychiatric problems and appears to be useful in attracting a diverse group of patients into public-sector funded treatment. PMID:21962726

  13. Basic epidemiology of opiate misuse substitution treatment in Belgium.

    PubMed

    Ledoux, Y

    2012-09-01

    The Substitution Treatment National Registry provided from mid 2006 till mid 2009 an exhaustive documentation on all patients being prescribed methadone or buprenorphine in Belgium. This endeavour was possible through cooperation of all community pharmacies and their representative organizations was supported at the time by the former Health federal minister. The Liberal belgian opiate medical substitution process authorizes untill now de facto any doctor to prescribe methadone and pharmacists are supported to dispense it. Results show the regional, provincial and county numbers of professionals and patients prevalence in the population. Nationwide, n = 16974 patients (prevalence for population aged 20-64: 26/10000) have been offered substitution from mid 2008 till mid 2009, n = 3390 pharmacies 164,4% of all pharmacies) and n = 2937 MDs (16,75% of all MDs) have been involved. Subutex or Suboxone have been dispensed to 11,1% of substitution patients with 7,4% receiving only buprenorphine on a yearly basis. Number of substitution patients by MD and prevalence by gender, age group and region are presented. Important variations are observed locally, possibly mirroring heroin addiction due to widespread access to substitution treatment. Younger patients are more prevalent in semi rural or border areas. The exhaustivity of available data enables also to observe patients quitting substitution altogether and a strong difference of maintenance rate is observed favoring methadone over buprenorphine. PMID:23697094

  14. Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain

    PubMed Central

    Khanna, Ish K; Pillarisetti, Sivaram

    2015-01-01

    Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about “ceiling effect” or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed μ-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other μ-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain. PMID:26672499

  15. Buprenorphine vs methadone treatment: A review of evidence in both developed and developing worlds

    PubMed Central

    Whelan, Paul J; Remski, Kimberly

    2012-01-01

    Heroin dependence is a major health and social problem associated with increased morbidity and mortality that adversely affects social circumstances, productivity, and healthcare and law enforcement costs. In the UK and many other Western countries, both methadone and buprenorphine are recommended by the relevant agencies for detoxification from heroin and for opioid maintenance therapy. However, despite obvious benefits due to its unique pharmacotherapy (eg, greatly reduced risk of overdose), buprenorphine has largely failed to overtake methadone in managing opioid addiction. The experience from the developing world (based on data from India) is similar. In this article we compare the advantages and disadvantages of the use methadone and buprenorphine for the treatment of opioid addiction from both a developed and developing world perspective; and explore some of the reasons why buprenorphine has not fulfilled the expectations predicted by many in the addictions field. PMID:22346191

  16. Extended vs Short-term Buprenorphine-Naloxone for Treatment of Opioid-Addicted Youth

    PubMed Central

    Woody, George E.; Poole, Sabrina A.; Subramaniam, Geetha; Dugosh, Karen; Bogenschutz, Michael; Abbott, Patrick; Patkar, Ashwin; Publicker, Mark; McCain, Karen; Potter, Jennifer Sharpe; Forman, Robert; Vetter, Victoria; McNicholas, Laura; Blaine, Jack; Lynch, Kevin G.; Fudala, Paul

    2008-01-01

    Context The usual treatment for opioid-addicted youth is detoxification and counseling. Extended medication-assisted therapy may be more helpful. Objective To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth. Design, Setting, and Patients Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine-naloxone or a 14-day taper (detox). Interventions Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling. Main Outcome Measure Opioid-positive urine test result at weeks 4, 8, and 12. Results The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 ( χ22 = 4.93, P = .09). At week 4, 59 detox patients had positive results (61%; 95% confidence interval [CI] = 47%-75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI = 14%-38%). At week 8, 53 detox patients had positive results (54%; 95% CI = 38%-70%) vs 52 12-week buprenorphine-naloxone patients (23%; 95% CI = 11%-35%). At week 12, 53 detox patients had positive results (51%; 95% CI = 35%-67%) vs 49 12-week buprenorphine-naloxone patients (43%; 95% CI = 29%-57%). By week 12, 16 of 78 detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients (70%; χ12 = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine-naloxone group reported less opioid use ( χ12 = 18.45, P < .001), less injecting ( χ12 = 6.00, P = .01), and less nonstudy addiction treatment ( χ12 = 25.82, P < .001). High levels of opioid use

  17. Buprenorphine-naloxone use in pregnancy for treatment of opioid dependence

    PubMed Central

    Dooley, Joe; Gerber-Finn, Lianne; Antone, Irwin; Guilfoyle, John; Blakelock, Brittany; Balfour-Boehm, Jazmyn; Hopman, Wilma M.; Jumah, Naana; Kelly, Len

    2016-01-01

    Abstract Objective To examine the maternal course and neonatal outcomes for women using buprenorphine-naloxone for opioid dependence in pregnancy. Design Retrospective cohort study comparing outcomes for the group of pregnant patients exposed to buprenorphine-naloxone with outcomes for those exposed to other narcotics and those not exposed to narcotics. Setting Northwestern Ontario obstetric program. Participants A total of 640 births in an 18-month period from July 1, 2013, to January 1, 2015. Main outcome measures Maternal outcomes included route and time of delivery, medical and surgical complications, out-of hospital deliveries, change in illicit drug use, and length of stay. Neonatal outcomes included stillbirths, incidence and severity of neonatal abstinence syndrome, birth weight, gestational age, Apgar scores, and incidence of congenital abnormalities. Results Thirty pregnant women used buprenorphine-naloxone for a mean (SD) of 18.8 (11.2) weeks; an additional 134 patients were exposed to other opioids; 476 pregnant women were not exposed to opioids. Maternal and neonatal outcomes were similar among the 3 groups, other than the expected clinically insignificant lower birth weights among those exposed to opioids other than buprenorphine-naloxone. Conclusion Buprenorphine-naloxone appears to be safe for use in pregnancy for opioid-dependence substitution therapy. Transferring a pregnant patient to another opioid agonist that has greater abuse potential might not be necessary.

  18. Changes in Quality of Life following Buprenorphine Treatment: Relationship with Treatment Retention and Illicit Opioid Use

    PubMed Central

    Mitchell, Shannon Gwin; Gryczynski, Jan; Schwartz, Robert P.; Myers, C. Patrick; O’Grady, Kevin E.; Olsen, Yngvild K.; Jaffe, Jerome H.

    2015-01-01

    Studies of substance abuse treatment outcomes that give priority to cessation of all drug use may obscure other tangible benefits of treatment that are important to patients. The aim of this study was to examine the association between changes in quality of life (QoL) and: (a) retention in treatment and (b) opioid use as measured by self-report and urine testing. Participants were 300 African American men and women starting outpatient buprenorphine treatment. Participants completed assessments at baseline, 3- and 6-months consisting of the World Health Organization’s Quality of Life brief scale, Addiction Severity Index, and urine testing for opioids. There were statistically significant increases over time across all four QoL domains: physical, psychological, environmental, and social. Self-reported frequency of opioid use was negatively associated with psychological QoL, but opioid urine test results were not significantly associated with any QoL domains. Continued treatment enrollment was significantly associated with higher psychological QoL and environmental QoL. Patients entering buprenorphine treatment experience improvements in QoL, which are amplified for patients who remain in treatment. Point-prevalence opiate urine test results obtained at each assessment were not associated with any of the QoL domains and may not accurately reflect improvements perceived by patients receiving buprenorphine treatment. PMID:25950595

  19. Changes in Quality of Life following Buprenorphine Treatment: Relationship with Treatment Retention and Illicit Opioid Use.

    PubMed

    Mitchell, Shannon Gwin; Gryczynski, Jan; Schwartz, Robert P; Myers, C Patrick; O'Grady, Kevin E; Olsen, Yngvild K; Jaffe, Jerome H

    2015-01-01

    Studies of substance abuse treatment outcomes that give priority to cessation of all drug use may obscure other tangible benefits of treatment that are important to patients. The aim of this study was to examine the association between changes in quality of life (QoL) and: (1) retention in treatment; and (2) opioid use as measured by self-report and urine testing. Participants were 300 African American men and women starting outpatient buprenorphine treatment. Participants completed assessments at baseline, three and six months consisting of the World Health Organization's Quality of Life brief scale, Addiction Severity Index, and urine testing for opioids. There were statistically significant increases over time across all four QoL domains: physical, psychological, environmental, and social. Self-reported frequency of opioid use was negatively associated with psychological QoL, but opioid urine test results were not significantly associated with any QoL domains. Continued treatment enrollment was significantly associated with higher psychological QoL and environmental QoL. Patients entering buprenorphine treatment experience improvements in QoL, which are amplified for patients who remain in treatment. Point-prevalence opiate urine test results obtained at each assessment were not associated with any of the QoL domains and may not accurately reflect improvements perceived by patients receiving buprenorphine treatment. PMID:25950595

  20. Clinical differences between opioid abuse classes ameliorated after 1 year of buprenorphine-medication assisted treatment.

    PubMed

    Tkacz, Joseph; Severt, Jamie; Kassed, Cheryl; Ruetsch, Charles

    2012-01-01

    This study compared the clinical and demographic profiles of three opioid-dependent user groups, and measured their response to 1 year of buprenorphine-medication assisted treatment. Opioid prescription, street, and combination (street + prescription) users completed the Addiction Severity Index multiple times over the course of one treatment year. Although groups differed on all measured demographics (P values <.05) and on six of seven Addiction Severity Index composite scores at induction (P values <.05), differences were ameliorated after 1 year. Findings highlight the disparities between the various opioid-dependent patient subpopulations and suggest that buprenorphine-medication assisted treatment is an effective treatment across user subtypes. PMID:22540432

  1. A case series of buprenorphine/naloxone treatment in a primary care practice.

    PubMed

    Doolittle, Benjamin; Becker, William

    2011-10-01

    Physicians' adoption of buprenorphine/naloxone treatment is hindered by concerns over feasibility, cost, and lack of comfort treating patients with addiction. We examined the use of buprenorphine/naloxone in a community practice by two generalist physicians without addiction training, employing a retrospective chart review. From 2006-2010, 228 patients with opiate abuse/dependence were treated with buprenorphine/naloxone using a home-induction protocol. Multiple co-morbidities including diabetes (23% of patients), hypertension (36%), Hepatitis C (43%), and depression (74%) were concurrently managed. In this diverse sample, 1/228 experienced precipitated withdrawal during induction. Of the convenience subsample analyzed (n = 28), 82% (+/-10%) had negative urine drug tests for opioids; 92% (+/-11%) were negative for cocaine; 88% (+/-12%) were positive for buprenorphine. This case series demonstrated feasibility and safety of a low-cost buprenorphine/naloxone home induction protocol employed by generalists. Concurrent treatment of multiple comorbidities conforms with the patient-centered medical home ideal. Randomized trials of this promising approach are needed. PMID:22014257

  2. Buprenorphine and methadone maintenance treatment of heroin addicts preserves immune function.

    PubMed

    Sacerdote, Paola; Franchi, Silvia; Gerra, Gilberto; Leccese, Vincenzo; Panerai, Alberto E; Somaini, Lorenzo

    2008-05-01

    Opiate addiction influences many physiological functions including immune responses. The objective of this study was to investigate the immune system function in heroin addicted patients submitted to methadone or buprenorphine maintenance treatment compared to untreated heroin addicts and healthy controls. Four groups were studied: group A included nine heroin addicted subjects, who were still injecting heroin; groups B and C were composed of 12 patients previously addicted to heroin, being treated with methadone (mean dosage 58+/-12.7 mg/day) or buprenorphine (mean dose 9.3+/-2.3mg/day) since at least 6 months; group D was composed of 15 sex and age matched healthy controls. Lymphoproliferation and peripheral mononuclear cell cultures production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokine TNF-alpha were evaluated in all the patients and controls. PHA-lymphoproliferation was lower in untreated heroin addicts than in controls, while it was normal in methadone and buprenorphine treated patients. An altered Th1/Th2 balance, characterized by reduced IL-4, IFN-gamma and TNF-alpha but normal IL-2 levels, was present in untreated heroin addicted subjects, while the Th1/Th2 balance was well conserved in the methadone and buprenorphine groups. These findings suggest that the immune system abnormalities in heroin addicted patients can be restored to almost normal values by controlled treatment with methadone and buprenorphine. PMID:18294814

  3. A Preliminary Randomized Controlled Trial of a Distress Tolerance Treatment for Opioid Dependent Persons Initiating Buprenorphine

    PubMed Central

    Stein, Michael D.; Herman, Debra S.; Moitra, Ethan; Hecht, Jacki; Lopez, Rosalie; Anderson, Bradley J; Brown, Richard A.

    2014-01-01

    Background Buprenorphine opioid agonist treatment (OAT) has established efficacy for treating opioid dependency but early relapse rates are high and are often associated with withdrawal-related or emotional distress. Methods To determine whether a novel distress tolerance (DT) intervention during buprenorphine initiation decreases opioid relapse, we conducted a preliminary randomized controlled trial with opioid-dependent outpatients. Participants received buprenorphine-naloxone induction and 3-months of maintenance buprenorphine plus seven, 50-minute manualized, individual sessions (DT vs. Health Education (HE) control) over a 28-day period, linked to clinician medication dosing visits, and beginning 2 days prior to buprenorphine induction. Primary outcomes included use of illicit opioids (positive defined as any self-reported use in the prior 28 days or detected by urine toxicology) and treatment drop out. Results Among 49 participants, the mean age was 41 years, 65.3% were male. Persons randomized to DT had lower rates of opioid use at all three monthly assessments, and at 3-months, 72% of HE participants were opioid positive compared with 62.5% of DT participants. Rates of dropout were 24% and 25% in the HE and DT arms, respectively. Conclusions This distress tolerance treatment produced a small, but not statistically significant reduction in opioid use during the first three months of treatment although no differences were found in drop-out rates between conditions. If replicated in a larger study, DT could offer clinicians a useful behavioral treatment to complement the effects of buprenorphine. Trial registered at clinicaltrials.org. Trial number NCT01556087. PMID:25510307

  4. Comment on "a comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes".

    PubMed

    Newman, Robert G; Gevertz, Susan G

    2013-01-01

    In a recent article, Lund et al sought to compare maternal and neonatal outcomes of various treatment regimens for opioid dependence during pregnancy.1 In their background, discussion the authors state that "In the United States buprenorphine plus naloxone [Suboxone(®)] … has been the preferred form of prescribed buprenorphine due to its reduced abuse liability relative to buprenorphine alone [Subutex(®)]." This claim is certainly consistent with the view of the firm that has manufactured and sold both products, Reckitt Benckiser. In September of 2011, the company announced that it was "… discontinuing distribution and sale of Subutex(®) tablets as we believe that mono product (product containing buprenorphine alone with no naloxone) creates a greater risk of misuse, abuse and diversion …".2 Supporting evidence for the alleged "reduced abuse liability" appears to be lacking, however, and evidence cannot be located in the two references cited by Dr. Lund and his co-authors, which in fact are silent on the subject of abuse potential.3,4 In contrast, it has been reported that the transition to buprenorphine/naloxone from the mono formulation has been associated with "… no reduction in injection risk behaviors among IDUs."5. PMID:23772177

  5. Policy implications of integrating buprenorphine/naloxone treatment and HIV care.

    PubMed

    Finkelstein, Ruth; Netherland, Julie; Sylla, Laurie; Gourevitch, Marc N; Cajina, Adan; Cheever, Laura

    2011-03-01

    Researchers, practitioners, and policymakers have long recognized the potential benefits of providing integrated substance abuse and medical care services, particularly for special populations such as people living with HIV/AIDS. Buprenorphine, an office-based pharmacological treatment for opioid dependence, offers new opportunities for integrating drug treatment into HIV care settings. However, the historical separation between the drug treatment and medical care systems has resulted in a host of policy barriers. The Buprenorphine and HIV Care Evaluation and Support initiative, a multisite demonstration project to assess the feasibility and effectiveness of integrating buprenorphine/naloxone into HIV care settings, provided an opportunity to evaluate if and how policy barriers affect efforts to integrate HIV care and addiction treatment. We found that financing issues, workforce and training issues, and the operational consequences of some conceptual differences between HIV care and addiction treatment are barriers to the full integration of buprenorphine into HIV care. We recommend changes to financing and reimbursement policies, programs to strengthen the addiction treatment skills of physicians, and cross training between the fields of addiction, medicine, drug treatment, and HIV medicine. By addressing some of the policy barriers to integration, this promising new treatment can help the thousands of people living with HIV/AIDS who are also opioid dependent. PMID:21317602

  6. Benzodiazepine use during buprenorphine treatment for opioid dependence: Clinical and safety outcomes

    PubMed Central

    Schuman-Olivier, Zev; Hoeppner, Bettina B.; Weiss, Roger D.; Borodovsky, Jacob; Shaffer, Howard J.; Albanese, Mark J.

    2013-01-01

    Background Prescribing benzodiazepines during buprenorphine treatment is a topic of active discussion. Clinical benefit is unclear. Overdose, accidental injury, and benzodiazepine misuse remain concerns. We examine the relationship between benzodiazepine misuse history, benzodiazepine prescription, and both clinical and safety outcomes during buprenorphine treatment. Methods We retrospectively examined outpatient buprenorphine treatment records, classifying patients by past-year benzodiazepine misuse history and approved benzodiazepine prescription at intake. Primary clinical outcomes included 12-month treatment retention and urine toxicology for illicit opioids. Primary safety outcomes included total emergency department (ED) visits and odds of an ED visit related to overdose or accidental injury during treatment. Results The 12-month treatment retention rate for the sample (N = 328) was 40%. Neither benzodiazepine misuse history nor benzodiazepine prescription was associated with treatment retention or illicit opioid use. Poisson regressions of ED visits during buprenorphine treatment revealed more ED visits among those with a benzodiazepine prescription versus those without (p < 0.001); benzodiazepine misuse history had no effect. The odds of an accidental injury-related ED visit during treatment were greater among those with a benzodiazepine prescription (OR: 3.7, p < 0.01), with an enhanced effect among females (OR: 4.7, p < 0.01). Overdose was not associated with benzodiazepine misuse history or prescription. Conclusions We found no effect of benzodiazepine prescriptions on opioid treatment outcomes; however, benzodiazepine prescription was associated with more frequent ED visits and accidental injuries, especially among females. When prescribing benzodiazepines during buprenorphine treatment, patients need more education about accidental injury risk. Alternative treatments for anxiety should be considered when possible, especially among females. PMID

  7. Buprenorphine for opioid dependence.

    PubMed

    Ling, Walter

    2009-05-01

    As a treatment agent for opioid dependence, buprenorphine is a nearly ideal medication at our current stage of medication development. Unlike methadone, buprenorphine dosage can be rapidly adjusted with minimal potential for inducing severe consequences. In addition to its intrinsic safety, buprenorphine's relatively low abuse liability in the combination product (i.e., with naloxone as Suboxone) makes it even more acceptable in regulatory quarters as well as to prescribing physicians. The approval of buprenorphine as a pharmacotherapy for opioid dependence returns to physicians the ability to treat their opioid-dependent patients with an effective opioid-based treatment for the first time in nearly 100 years. Buprenorphine is an opioid, however, and potential for misuse remains, even in combination with naloxone. Whether buprenorphine will be increasingly accepted as a treatment for opioid-dependent patients depends on clinicians recognizing the advantages of its uniquely useful properties while still heeding the need to manage their patients' therapy with reasonable vigilance. PMID:19402772

  8. The evidence doesn't justify steps by state Medicaid programs to restrict opioid addiction treatment with buprenorphine.

    PubMed

    Clark, Robin E; Samnaliev, Mihail; Baxter, Jeffrey D; Leung, Gary Y

    2011-08-01

    Many state Medicaid programs restrict access to buprenorphine, a prescription medication that relieves withdrawal symptoms for people addicted to heroin or other opiates. The reason is that officials fear that the drug is costlier or less safe than other therapies such as methadone. To find out if this is true, we compared spending, the use of services related to drug-use relapses, and mortality for 33,923 Massachusetts Medicaid beneficiaries receiving either buprenorphine, methadone, drug-free treatment, or no treatment during the period 2003-07. Buprenorphine appears to have significantly expanded access to treatment because the drug can be prescribed by a physician and taken at home compared with methadone, which by law must be administered at an approved clinic. Buprenorphine was associated with more relapse-related services but $1,330 lower mean annual spending than methadone when used for maintenance treatment. Mortality rates were similar for buprenorphine and methadone. By contrast, mortality rates were 75 percent higher among those receiving drug-free treatment, and more than twice as high among those receiving no treatment, compared to those receiving buprenorphine. The evidence does not support rationing buprenorphine to save money or ensure safety. PMID:21821560

  9. Developing and Implementing a New Prison-Based Buprenorphine Treatment Program

    ERIC Educational Resources Information Center

    Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.; Fitzgerald, Terrence T.

    2010-01-01

    Research suggests that buprenorphine treatment may be a promising intervention for incarcerated individuals with heroin addiction histories. However, its implementation varies from corrections-based methadone because of unique challenges regarding dosing, administration, and regulation. Describing the first randomized clinical trial of…

  10. French Experience with Buprenorphine : Do Physicians Follow the Guidelines?

    PubMed Central

    Guillou Landreat, Morgane; Rozaire, Charles; Guillet, Jean yves; Victorri Vigneau, Caroline; Le Reste, Jean Yves; Grall Bronnec, Marie

    2015-01-01

    Opiate dependence affects about 15,479,000 people worldwide. The effectiveness of opiate substitution treatments (OST) has been widely demonstrated. Buprenorphine plays a particular role in opiate dependence care provision in France. It is widely prescribed by physicians and national opiate substitution treatment guidelines have been available since 2004. In order to study the prescribing of buprenorphine, we used a questionnaire sent by email, to a large sample of physicians. These physicians were either in practice, or belonged to an addiction treatment network or a hospital. The main objective of this work was to measure the extent to which the theoretical, clinical attitude of physicians towards prescribing buprenorphine (BHD) complied with the statutory guidelines. We showed that the physicians we interviewed rarely took into account the guidelines regarding buprenorphine prescription. The actual prescribing of Buprenorphine differed from the guidelines. Only 42% of independent Family Physicians (FPs), working outside the national health care system, had prescribed buprenorphine as a first-time prescription and 40% of FPs do not follow up patients on buprenorphine. In terms of compliance with the guidelines, 55% of FPs gave theoretical answers that only partially complied with the guidelines. The variations in compliance with the guidelines was noted according to different variables and took into particular account whether the physician were affiliated to a network or in training. PMID:26479400

  11. Compliance with buprenorphine medication-assisted treatment and relapse to opioid use.

    PubMed

    Tkacz, Joseph; Severt, Jamie; Cacciola, John; Ruetsch, Charles

    2012-01-01

    Opioid dependence (OD), often characterized as a chronic relapsing disorder, affects millions of people worldwide. The purpose of this study was to examine the effect of compliance with buprenorphine on reducing relapse among a sample of patients in treatment for OD. Patients new to buprenorphine (N = 703) completed the Addiction Severity Index (ASI) at baseline, and at 1, 2, and 3 months postbaseline. The ASI is a semistructured interview designed to measure problem severity in seven functional areas known to be affected by alcohol and drug dependence. Compliance was defined as taking buprenorphine medication on at least 22 of the past 28 days (80%), while relapse classification was based on resumed use of opioids during the follow-up period (months 2 and 3). Relapse was regressed onto demographic indicators, baseline ASI composite scores, and compliance with buprenorphine. Noncompliant patients were over 10 times more likely to relapse than those who were compliant (exp β= 10.55; p < .001). Neither demographics nor baseline ASI composite scores were predictive of relapse (p's > .05). Compliance with medication-assisted treatment supports abstinence, essential for patient recovery. Understanding the factors that drive treatment compliance and noncompliance may assist providers in supporting patient compliance and recovery.  PMID:22211347

  12. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40

    ERIC Educational Resources Information Center

    Boone, Margaret; Brown, Nancy J.; Moon, Mary A.; Schuman, Deborah J.; Thomas, Josephine; Wright, Denise L.

    2004-01-01

    This Treatment Improvement Protocol (TIP) addresses the clinical use of buprenorphine in the treatment of opioid addiction. TIPs are best-practice guidelines for the treatment of substance use disorders that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel of experts…

  13. Practice Guidance for Buprenorphine for the Treatment of Opioid Use Disorders: Results of an Expert Panel Process

    PubMed Central

    Farmer, Carrie M.; Lindsay, Dawn; Williams, Jessica; Ayers, Amanda; Schuster, James; Cilia, Alyssa; Flaherty, Michael T.; Mandell, Todd; Gordon, Adam J.; Stein, Bradley D.

    2015-01-01

    Background Although numbers of physicians credentialed to prescribe buprenorphine has increased over time, many credentialed physicians may be reluctant to treat individuals with opioid use disorders due to discomfort with prescribing buprenorphine. Though prescribing physicians are required to complete a training course, many have questions about buprenorphine and treatment guidelines have not been updated to reflect clinical experience in recent years. We report on an expert panel process to update and expand buprenorphine guidelines. Methods We identified candidate guidelines through expert opinion and a review of the literature and used a modified RAND/UCLA Appropriateness Method to assess the validity of the candidate guidelines. An expert panel completed two rounds of rating, with a meeting to discuss the guidelines between the first and second rating. Results Through the rating process, expert panel members rated 90 candidate guideline statements across eight domains, including candidacy for buprenorphine treatment, dosing of buprenorphine, psychosocial counseling, and treatment of co-occurring depression and anxiety. A total of 65 guideline statements (72%) were rated as valid. Expert panel members had agreement in some areas, such as the treatment of co-occurring mental health problems, but disagreement in others, including the appropriate dosing of buprenorphine given patient complexities. Conclusions Through an expert panel process, we developed an updated and expanded set of buprenorphine treatment guidelines; this additional guidance may increase credentialed physicians’ comfort with prescribing buprenorphine to patients with opioid use disorders. Future efforts should focus on appropriate dosing guidance and ensuring that guidelines can be adapted to a variety of practice settings. PMID:25844527

  14. Buprenorphine and nor-buprenorphine levels in head hair samples from former heroin users under Suboxone® treatment.

    PubMed

    Belivanis, Stamatis; Tzatzarakis, Manolis N; Vakonaki, Elena; Kovatsi, Leda; Mantsi, Mary; Alegakis, Athanasios; Kavvalakis, Matthaios P; Vynias, Dionisios; Tsatsakis, Aristidis M

    2014-06-01

    In the current study, buprenorphine (BUP) and its major metabolite, nor-buprenorphine (NBUP), were determined in hair samples from former heroin users following Suboxone® treatment. Hair samples from 36 subjects were analyzed. The drugs of interest were isolated from hair by solid-liquid extraction with methanol and were determined by liquid chromatography-mass spectrometry, using an electrospray ionization interface. The analytical parameters of the method (such as linearity, limits of quantification, recovery, accuracy, and precision) were determined. The inter-quartile range of BUP levels was from 11.4 to 37.4 pg/mg (mean value 56.6 pg/mg) for the proximal hair segment, from 5.8 to 43.3 pg/mg for the middle hair segment (mean value 25.3 pg/mg), while a range from 4.3 to 33.9 pg/mg (mean value 105.2 pg/mg) for the distant to the root hair segment was determined. For NBUP the corresponding inter-quartile range was from 27.0 to 147.6 for the proximal segment (mean value 95.4 pg/mg), from 21.5 to 164.7 pg/mg for the middle segment (mean value 102.0 pg/mg) and from 20.4 to 103.6 pg/mg for the distant segment (mean value 156.8 pg/mg). The mean BUP/NBUP concentration ratio was 0.5. The daily dose of Suboxone® correlated significantly with BUP and NBUP levels in hair (p = 0.001 and p = 0.023) as well as with the BUP/NBUP ratio (p = 0.010). No significant correlation was found between the levels of BUP and NBUP and the duration of Suboxone® administration. The developed and validated method was successfully used for the determination of BUP and NBUP in hair samples collected from former heroin users under Suboxone® treatment. PMID:24817054

  15. [Guidelines for substitution treatments in prison populations].

    PubMed

    Michel, L; Maguet, O

    2005-01-01

    Care access for the drug addict patients in prison (in particular for the treatments of substitution) in France is very unequal from one establishment to another. This reflects the great variability of the practices of substitution and especially the absence of consensus on the methods of adaptation of these practices to the prison environment. Because of difficulties expressed by prisoners and medical staff on this subject and of stakes (let us recall that approximately 30% of the prisoners are dependent or abusers of one or more psychoactive substances), the formulation of recommendations or of a good practices guide of substitution in prison appeared necessary. Work that we detail here answers a ordering of the Advisory Commission of the Treatments of Substitution (September 2001) whose authors are members. It was presented at the session April 2003. It results from the confrontation of a review of the literature (including legal texts and official reports concerning substitution, the organization of the care in prison environment and the lawful framework), with a vast investigation. The latter was carried out near medical staff (22 prisons), penitentiary staff (3 prisons, 27 people met including directors of these establishments) and prisoners (7 establishments, 28 prisoners met) in the form of individual talks (semi-directing interviews with evaluation of the type of existing device and its knowledge by the penitentiary staff and the prisoners; statement of the suggestions, needs and requests of the medical, penitentiary staffs and of the prisoners). In the whole visited prisons, 7.8% (870) of the prisoners received substitution treatments (6.35% by buprenorphine, 1.44% by methadone), representing a proportion of substituted drug addicts (870 substituted for an evaluation of 3,350 prisoners drug addicts among the 11,168 prisoners of the 22 visited prisons) notably lower than that in free environment (56%, ie 96,000 substituted for an evaluated population of

  16. Treatment Outcomes of African American Buprenorphine Patients by Parole and Probation Status

    PubMed Central

    Mitchell, Shannon Gwin; Gryczynski, Jan; Kelly, Sharon M.; O’Grady, Kevin E.; Jaffe, Jerome H.; Olsen, Yngvild K.; Schwartz, Robert P.

    2014-01-01

    This secondary analysis compared outcomes of African-American adults newly-admitted to buprenorphine treatment who were on parole and probation to patients who were not under criminal justice supervision. Buprenorphine patients (N=300) were randomly assigned to receive either Intensive Outpatient Treatment (IOP) or Standard Outpatient Treatment (OP) treatment and were assessed at baseline, 3- and 6-months. There were no differences between groups in treatment retention. Among probationers/parolees, IOP was associated with lower 3-month treatment retention compared to OP, but among participants not on probation/parole the relationship was reversed (p=.004). Both conditions showed significant declines in heroin and cocaine use, illegal activity, and in meeting DSM-IV criteria for opioid and cocaine dependence. Probationers/parolees reported lower frequency of illegal activities at 3-months compared to non-probationers/parolees (p=.007). Buprenorphine treatment should be made more widely available to individuals on parole/probation as they respond as well to treatment as patients not supervised by the criminal justice system. PMID:25364037

  17. Direct Injection LC-MS-MS Analysis of Opiates, Methamphetamine, Buprenorphine, Methadone and Their Metabolites in Oral Fluid from Substitution Therapy Patients.

    PubMed

    Liu, Hsiu-Chuan; Lee, Hsi-Tzu; Hsu, Ya-Ching; Huang, Mei-Han; Liu, Ray H; Chen, Tai-Jui; Lin, Dong-Liang

    2015-01-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed, validated and applied to simultaneous analysis of oral fluid samples for the following 10 analytes: methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, morphine, codeine, 6-acetylmorphine, 6-acetylcodeine, amphetamine, and methamphetamine. The oral fluid sample was briefly centrifuged and the supernatant was directly injected into the LC-MS-MS system operated under reverse-phase chromatography and electrospray ionization (ESI). Deuterated analogs of the analytes were adopted as the internal standards and found to be effective (except for buprenorphine) to compensate for potential matrix effects. Each analytical run took <10 min. Linearity range (r(2) > 0.99) established for buprenorphine and the other nine analytes were 5-100 and 1-100 ng/mL. Intra- and interday precision (% CV) ranges for the 10 analytes were 0.87-12.2% and 1.27-12.8%, while the corresponding accuracy (%) ranges were 91.8-113% and 91.9-111%. Limits of detection and quantitation established for these 10 analytes were in the ranges of 0.1-1.0 and 0.25-1.0 ng/mL (5 ng/mL for buprenorphine). The method was successfully applied to the analysis of 62 oral fluid specimens collected from patients participating in methadone and buprenorphine substitution therapy programs. Analytical results of methadone and buprenorphine were compared with data derived from GC-MS analysis and found to be compatible. Overall, the direct injection LC-MS-MS method performed well, permitting rapid analysis of oral fluid samples for simultaneous quantification of methadone, buprenorphine, opiate and amphetamine drug categories without extensive sample preparation steps. PMID:25935159

  18. Buprenorphine for office-based treatment of patients with opioid addiction.

    PubMed

    Manlandro, James J

    2005-06-01

    The Drug Addiction Treatment Act of 2000 (DATA 2000) was established to create a new paradigm for medication-assisted treatment of opiate addiction in the United States. Before enactment of DATA 2000, the use of opioid medications to treat opioid addiction was permissible only in federally approved treatment programs, ie, methadone clinics. The only medications permitted were Schedule II drugs (eg, methadone and l-a-acetylmethadol [LAAM]), which could only be dispensed, not prescribed. Under provisions of DATA 2000, qualified physicians in a medical office and other appropriate settings outside the opioid treatment program system may prescribe or dispense (or both), Schedule III, IV, and V opioid medications for treatment of opioid addiction if such medications have been specifically approved by the the US Food and Drug Administration for that indication. Opioid addiction treatment programs were commonly known as methadone clinics. They now may also dispense buprenorphine hydrochloride and the buprenorphine hydrochloride-naloxone combination. The information in this article is extracted (with revision) from: Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHS Publication No. (SMA) 04-3939. Rockville, Md: Substance Abuse and Mental Health Services Administration; 2004. The Clinical Guidelines document is in the public domain except for material indicated as reprinted from a copyrighted source. The author served on both the Expert Panel and the Consensus Panel that produced the guidelines, available in portable document format at http://buprenorphine.samhsa.gov/Bup%20Guidelines.pdf. PMID:16118361

  19. Failure to identify or effectively manage prescription opioid dependence acted as a gateway to heroin use-buprenorphine/naloxone treatment and recovery in a surgical patient.

    PubMed

    Conroy, Stephen; Hill, Duncan

    2014-01-01

    The prescribing of opioid pain medication has increased markedly in recent years, with strong opioid dispensing increasing 18-fold in Tayside, Scotland since 1995. Despite this, little data is available to quantify the problem of opioid pain medication dependence (OPD) and until recently there was little guidance on best-practice treatment. We report the case of a young mother prescribed dihydrocodeine for postoperative pain relief who became opioid dependent. When her prescription was stopped without support, she briefly used heroin to overcome her withdrawal. After re-exposure to dihydrocodeine following surgery 9 years later and treatment with methadone for dependency, she was transferred to buprenorphine/naloxone. In our clinical experience and in agreement with Department of Health and Royal College of General Practitioner guidance, buprenorphine/naloxone is the preferred opioid substitution treatment for OPD. Our patient remains within her treatment programme and has returned to work on buprenorphine 16 mg/naloxone 4 mg in conjunction with social and psychological support. PMID:25519865

  20. Emergency Department–Initiated Buprenorphine/Naloxone Treatment for Opioid Dependence

    PubMed Central

    D’Onofrio, Gail; O’Connor, Patrick G.; Pantalon, Michael V.; Chawarski, Marek C.; Busch, Susan H.; Owens, Patricia H.; Bernstein, Steven L.; Fiellin, David A.

    2015-01-01

    IMPORTANCE Opioid-dependent patients often use the emergency department (ED) for medical care. OBJECTIVE To test the efficacy of 3 interventions for opioid dependence: (1) screening and referral to treatment (referral); (2) screening, brief intervention, and facilitated referral to community-based treatment services (brief intervention); and (3) screening, brief intervention, ED-initiated treatment with buprenorphine/naloxone, and referral to primary care for 10-week follow-up (buprenorphine). DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial involving 329 opioid-dependent patients who were treated at an urban teaching hospital ED from April 7, 2009, through June 25, 2013. INTERVENTIONS After screening, 104 patients were randomized to the referral group, 111 to the brief intervention group, and 114 to the buprenorphine treatment group. MAIN OUTCOMES AND MEASURES Enrollment in and receiving addiction treatment 30 days after randomization was the primary outcome. Self-reported days of illicit opioid use, urine testing for illicit opioids, human immunodeficiency virus (HIV) risk, and use of addiction treatment services were the secondary outcomes. RESULTS Seventy-eight percent of patients in the buprenorphine group (89 of 114 [95% CI, 70%-85%]) vs 37% in the referral group (38 of 102 [95% CI, 28%-47%]) and 45% in the brief intervention group (50 of 111 [95% CI, 36%-54%]) were engaged in addiction treatment on the 30th day after randomization (P < .001). The buprenorphine group reduced the number of days of illicit opioid use per week from 5.4 days (95% CI, 5.1-5.7) to 0.9 days (95% CI, 0.5-1.3) vs a reduction from 5.4 days (95% CI, 5.1-5.7) to 2.3 days (95% CI, 1.7-3.0) in the referral group and from 5.6 days (95% CI, 5.3-5.9) to 2.4 days (95% CI, 1.8-3.0) in the brief intervention group (P < .001 for both time and intervention effects; P = .02 for the interaction effect). The rates of urine samples that tested negative for opioids did not differ

  1. Two Models of Integrating Buprenorphine Treatment and Medical Staff within Formerly "Drug-Free" Outpatient Programs.

    PubMed

    Monico, Laura; Schwartz, Robert P; Gryczynski, Jan; O'Grady, Kevin E; Mitchell, Shannon Gwin

    2016-01-01

    "Drug-free" outpatient programs deliver treatment to the largest number of patients of all treatment modalities in the U.S., providing a significant opportunity to expand access to medication treatments for substance use disorders. This analysis examined staff perceptions of organizational dynamics associated with the delivery of buprenorphine maintenance within three formerly "drug-free" outpatient treatment programs. Semi-structured interviews (N = 15) were conducted with counseling and medical staff, and respondents were predominantly African American (n = 11) and female (n = 12). Themes and concepts related to medical staff integration emerged through an inductive and iterative coding process using Atlas.ti qualitative analysis software. Two treatment clinics incorporated buprenorphine maintenance into their programs using a co-located model of care. Their staff generally reported greater intra-organizational discord regarding the best ways to combine medication and counseling compared to the clinic using an integrated model of care. Co-located program staff reported less communication between medical and clinical staff, which contributed to some uncertainty about proper dosing and concerns about the potential for medication diversion. Clinics that shift from "drug-free" to incorporating buprenorphine maintenance should consider which model of care they wish to adapt and how to train staff and structure staff communication. PMID:26940870

  2. Opioid substitution treatment in New Zealand: a 40 year perspective.

    PubMed

    Deering, Daryle; Sellman, J Douglas; Adamson, Simon

    2014-07-01

    We provide an overview of the history and philosophy of the treatment for opioid dependence, which has been dominated by methadone substitution treatment for the past 40 years in New Zealand. Although changes in approach have occurred over this time, influenced by various sociopolitical events and changing ideologies, opioid substitution treatment has still "not come of age". It remains undermined by stigma and risk concerns associated with methadone and has struggled to be accessible and attractive to illicit opioid drug users, comprehensive and integrated into mainstream health care. However, the introduction in 2012 of Pharmac-subsidised buprenorphine combined with naloxone (Suboxone) in the context of an emerging trend towards a broader recovery and well-being orientation could signal a new era in treatment. The availability of buprenorphine-naloxone may also facilitate a further shift in treatment from primarily siloed specialist addiction services to integrated primary care services. This shift will help reduce stigma, promote patient self-management and community integration and align opioid substitution treatment with treatment for other chronic health conditions such as diabetes and asthma. PMID:24997702

  3. Buprenorphine pharmacotherapy and behavioral treatment: comparison of outcomes among prescription opioid users, heroin users and combination users.

    PubMed

    Nielsen, Suzanne; Hillhouse, Maureen; Mooney, Larissa; Ang, Alfonso; Ling, Walter

    2015-01-01

    Most research examining buprenorphine has been conducted with heroin users. Few studies have examined buprenorphine pharmacotherapy for prescription opioid users. Data were from a randomized controlled trial of behavioral treatment provided for 16weeks on a platform of buprenorphine pharmacotherapy and medication management. We compared heroin (H, n=54), prescription opioid (PO, n=54) and combination heroin+prescription opioid (POH, n=71) users to test the hypothesis that PO users will have better treatment outcomes compared with heroin users. The PO group provided more opioid-negative urine drug screens over the combined treatment period (PO:70%, POH:40%, H:38%, p<0.001) and at the end of the combined treatment period (PO:65%, POH:31%, H:33%, p<0.001). Retention was lowest in the H group (PO:80%, POH:65%, H:57%, p=0.039). There was no significant difference in buprenorphine dose between the groups. PO users appear to have better outcomes in buprenorphine pharmacotherapy compared to those reporting any heroin use, confirming that buprenorphine pharmacotherapy is effective in PO users. PMID:25065489

  4. Motivational Assessment of Non-Treatment Buprenorphine Research Participation in Heroin Dependent Individuals

    PubMed Central

    Papke, Gina; Greenwald, Mark K.

    2011-01-01

    Background Heroin abuse remains an important public health problem, particularly in economically disadvantaged areas. Insight into this problem is gained from interviewing addicted individuals. However, we lack systematic data on factors that motivate heroin users to participate in non-treatment research that offers both financial incentives (compensation) and non-financial incentives (e.g., short-term medication). Aim To better understand the relative importance of several types of personal motivations to participate in non-treatment buprenorphine research, and to relate self-motivations to social, economic, demographic and drug use factors. Methods Heroin dependent volunteers (N = 235 total; 57 female and 178 male; 136 African American, 86 Caucasian, and 13 Other) applied for non-therapeutic buprenorphine research in an urban outpatient setting from 2004–2008. We conducted a semi-structured behavioral economic interview, after which participants ranked 11 possible motivations for research participation. Results Although the study was repeatedly described as non-treatment research involving buprenorphine, participants often ranked some treatment-related motivations as important (wanting to reduce/stop heroin use, needing a medication to get stabilized/detoxify). Some motivations correlated with income, heroin use, and years since marketing of buprenorphine. Two dimensions emerged from principal component analysis of motivation rankings: (1) treatment motivation vs. greater immediate needs, and (2) commitment to trying alternatives vs. a more accepting attitude toward traditional interventions. In summary, heroin addicts’ self-motivations to engage in non-therapeutic research are complex – they value economic gain but not exclusively or primarily – and relate to variables such as socioeconomic factors and drug use. PMID:22137646

  5. Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method

    PubMed Central

    Hämmig, Robert; Kemter, Antje; Strasser, Johannes; von Bardeleben, Ulrich; Gugger, Barbara; Walter, Marc; Dürsteler, Kenneth M; Vogel, Marc

    2016-01-01

    Background Buprenorphine is a partial µ-opioid receptor agonist used for maintenance treatment of opioid dependence. Because of the partial agonism and high receptor affinity, it may precipitate withdrawal symptoms during induction in persons on full µ-opioid receptor agonists. Therefore, current guidelines and drug labels recommend leaving a sufficient time period since the last full agonist use, waiting for clear and objective withdrawal symptoms, and reducing pre-existing full agonist therapies before administering buprenorphine. However, even with these precautions, for many patients the induction of buprenorphine is a difficult experience, due to withdrawal symptoms. Furthermore, tapering of the full agonist bears the risk of relapse to illicit opioid use. Cases We present two cases of successful initiation of buprenorphine treatment with the Bernese method, ie, gradual induction overlapping with full agonist use. The first patient began buprenorphine with overlapping street heroin use after repeatedly experiencing relapse, withdrawal, and trauma reactivation symptoms during conventional induction. The second patient was maintained on high doses of diacetylmorphine (ie, pharmaceutical heroin) and methadone during induction. Both patients tolerated the induction procedure well and reported only mild withdrawal symptoms. Discussion Overlapping induction of buprenorphine maintenance treatment with full µ-opioid receptor agonist use is feasible and may be associated with better tolerability and acceptability in some patients compared to the conventional method of induction. PMID:27499655

  6. A Pilot Study of a Distress Tolerance Treatment for Opiate Dependent Patients Initiating Buprenorphine: Rationale, Methodology, and Outcomes

    PubMed Central

    Brown, Richard A.; Bloom, Erika Litvin; Hecht, Jacki; Moitra, Ethan; Herman, Debra S.; Stein, Michael D.

    2016-01-01

    Buprenorphine, an opioid that is a long-acting partial opiate agonist, is an efficacious treatment for opiate dependence that is growing in popularity. Nevertheless, evidence suggests that many patients will lapse within the first week of treatment, and that lapses are often associated with withdrawal-related or emotional distress. Recent research suggests that individuals’ reactions to this distress may represent an important treatment target. In the current study, we describe the development and outcomes from a preliminary pilot evaluation (N = 5) of a novel distress tolerance treatment for individuals initiating buprenorphine. This treatment incorporates exposure-based and acceptance-based treatment approaches that we have previously applied to the treatment of tobacco dependence. Results from this pilot study establish the feasibility and acceptability of this approach. We are now conducting a randomized controlled trial of this treatment that we hope will yield clinically significant findings and offer clinicians an efficacious behavioral treatment to complement the effects of buprenorphine. PMID:24973401

  7. Initial response as a predictor of 12-week buprenorphine-naloxone treatment response in a prescription opioid dependent population

    PubMed Central

    McDermott, Katherine A.; Griffin, Margaret L.; Connery, Hilary S.; Hilario, E. Yvette; Fiellin, David A.; Fitzmaurice, Garrett M.; Weiss, Roger D.

    2015-01-01

    Objective Initial medication response has been shown to predict treatment outcome across a variety of substance use disorders, but no studies have examined the predictive power of initial response to buprenorphine-naloxone in the treatment of prescription opioid dependence. We therefore conducted a secondary analysis of data from the Prescription Opioid Addiction Treatment Study to determine whether initial response to buprenorphine-naloxone predicted 12-week treatment outcome in a prescription opioid-dependent population. Method Using data from a multi-site, randomized controlled trial of buprenorphine-naloxone plus counseling for DSM-IV prescription opioid dependence (June 2006–July 2009), we conducted a secondary analysis to investigate the relationship between initial medication response and 12-week treatment outcome to establish how soon the efficacy of buprenorphine-naloxone could be predicted. Outcomes were determined from the Substance Use Report, a self-report measure of substance use, and confirmatory urinalysis. Predictive values were calculated to determine the importance of abstinence vs. use at various time points within the first month of treatment (week 1, weeks 1–2, 1–3, or 1–4) in predicting successful vs. unsuccessful treatment outcome (based on abstinence or near-abstinence from opioids) in the last 4 weeks of buprenorphine-naloxone treatment (weeks 9–12). Results Outcome was best predicted by medication response after two weeks of treatment. Two weeks of initial abstinence was moderately predictive of treatment success (positive predictive value = 71%), while opioid use in both of the first two weeks was strongly predictive of unsuccessful treatment outcome (negative predictive value (NPV) = 84%), especially when successful outcome was defined as total abstinence from opioids in weeks 9–12 (NPV = 94%). Conclusion Evaluating prescription opioid-dependent patients after two weeks of buprenorphine-naloxone treatment may help determine

  8. The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales

    PubMed Central

    Marteau, Dave

    2015-01-01

    Objective To examine the population-wide overdose risk emerging from the prescription of methadone and buprenorphine for opioid substitution treatment in England and Wales. Design Retrospective administrative data study. Setting National databases for England and Wales. Participants/cases Drug-related mortality data were drawn from the Office for National Statistics, and prescription data for methadone and buprenorphine were obtained from the National Health Service for the years 2007–2012. During this 6-year period, a total of 2366 methadone-related deaths and 52 buprenorphine-related deaths were registered, corresponding to 17 333 163 methadone and 2 602 374 buprenorphine prescriptions issued. The analysis encompassed poisoning deaths among members of the wider population of England and Wales who consumed, but were not prescribed these medications, in addition to patients prescribed methadone or buprenorphine. Main outcome measures Mortality risk: substance-specific overdose rate per 1000 prescriptions issued; relative risk ratio of methadone in relation to buprenorphine. Results During the years 2007–2012, the pooled overdose death rate was 0.137/1000 prescriptions of methadone, compared to 0.022/1000 prescriptions of buprenorphine (including buprenorphine-naloxone). The analysis generated a relative risk ratio of 6.23 (95% CI 4.79 to 8.10) of methadone in relation to buprenorphine. UK Borders Agency data were taken into consideration and revealed that only negligible amounts of methadone and buprenorphine were seized on entering UK territory between 2007 and 2012, suggesting domestic diversion. Conclusions Our analysis of the relative safety of buprenorphine and methadone for opioid substitution treatment reveals that buprenorphine is six times safer than methadone with regard to overdose risk among the general population. Clinicians should be aware of the increased risk of prescribing methadone, and tighter regulations are needed to prevent its

  9. Buprenorphine Buccal (chronic pain)

    MedlinePlus

    ... doctor may decrease your dose if you experience side effects. Tell your doctor if you feel that your pain is not controlled or if you experience side effects during your treatment with buprenorphine (Belbuca). Do not ...

  10. Sexual Dysfunction in Heroin Dependents: A Comparison between Methadone and Buprenorphine Maintenance Treatment

    PubMed Central

    Yee, Anne; Danaee, Mahmoud; Loh, Huai Seng; Sulaiman, Ahmad Hatim; Ng, Chong Guan

    2016-01-01

    Introduction Methadone has long been regarded as an effective treatment for opioid dependence. However, many patients discontinue maintenance therapy because of its side effects, with one of the most common being sexual dysfunction. Buprenorphine is a proven alternative to methadone. This study aimed to investigate sexual dysfunction in opioid-dependent men on buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT). The secondary aim was to investigate the correlation between sexual dysfunction and the quality of life in these patients. Methods Two hundred thirty-eight men participated in this cross-sectional study. Four questionnaires were used, the Mini International Neuropsychiatric Interview, Opiate Treatment Index, Malay version of the International Index of Erectile Function 15 (Mal-IIEF-15), and World Health Organization Quality of Life-BREF Scale. Multivariate analysis of covariance was used to examine the relationship between MMT and BMT and the Mal-IIEF 15 scores while controlling for all the possible confounders. Results The study population consisted of 171 patients (71.8%) on MMT and 67 (28.2%) on BMT. Patients in the MMT group who had a sexual partner scored significantly lower in the sexual desire domain (p < 0.012) and overall satisfaction (p = 0.043) domain compared with their counterparts in the BMT group. Similarly, patients in the MMT group without a sexual partner scored significantly lower in the orgasmic function domain (p = 0.008) compared with those in the BMT group without a partner. Intercourse satisfaction (p = 0.026) and overall satisfaction (p = 0.039) were significantly associated with the social relationships domain after adjusting for significantly correlated sociodemographic variables. Conclusions Sexual functioning is critical for improving the quality of life in patients in an opioid rehabilitation program. Our study showed that buprenorphine causes less sexual dysfunction than methadone. Thus

  11. Growth In Buprenorphine Waivers For Physicians Increased Potential Access To Opioid Agonist Treatment, 2002-11.

    PubMed

    Dick, Andrew W; Pacula, Rosalie L; Gordon, Adam J; Sorbero, Mark; Burns, Rachel M; Leslie, Douglas; Stein, Bradley D

    2015-06-01

    Opioid use disorders are a significant public health problem, affecting two million people in the United States. Treatment with buprenorphine, methadone, or both is predominantly offered in methadone clinics, yet many people do not receive the treatment they need. In 2002 the Food and Drug Administration approved buprenorphine for prescription by physicians who completed a course and received a waiver from the Drug Enforcement Administration, exempting them from requirements in the Controlled Substances Act. To determine the waiver program's impact on the availability of opioid agonist treatment, we analyzed data for the period 2002-11 to identify counties with opioid treatment shortages. We found that the percentage of counties with a shortage of waivered physicians fell sharply, from 98.9 percent in 2002 to 46.8 percent in 2011. As a result, the percentage of the US population residing in what we classified as opioid treatment shortage counties declined from 48.6 percent in 2002 to 10.4 percent in 2011. These findings suggest that the increase in waivered physicians has dramatically increased potential access to opioid agonist treatment. Policy makers should focus their efforts on further increasing the number and geographical distribution of physicians, particularly in more rural counties, where prescription opioid misuse is rapidly growing. PMID:26056209

  12. Buprenorphine Treatment and 12-step Meeting Attendance: Conflicts, Compatibilities, and Patient Outcomes.

    PubMed

    Monico, Laura B; Gryczynski, Jan; Mitchell, Shannon Gwin; Schwartz, Robert P; O'Grady, Kevin E; Jaffe, Jerome H

    2015-10-01

    This analysis examines patient experiences and outcomes with 12-step recovery group attendance during buprenorphine maintenance treatment (BMT), two approaches with traditionally divergent philosophies regarding opioid medications for treatment of opioid use disorder. Using quantitative (n = 300) and qualitative (n = 20) data collected during a randomized trial of counseling services in buprenorphine treatment, this mixed-methods analysis of African Americans in BMT finds the number of NA meetings attended in the prior 6 months was associated with a higher rate of retention in BMT (p < .001) and heroin/cocaine abstinence at 6 month follow-up (p = .005). However, patients whose counselors required them to attend 12-step meetings did not have better outcomes than patients not required to attend such meetings. Qualitative narratives highlighted patients' strategies for managing dissonant viewpoints on BMT and disclosing BMT status in community 12-step meetings. Twelve-step meeting attendance is associated with better outcomes for BMT patients over the first 6 months of treatment. However, there is no benefit to requiring meeting attendance as a condition of treatment, and clinicians should be aware of potential philosophical conflicts between 12-step and BMT approaches. PMID:25986647

  13. Substitution treatment for opioid addicts in Germany

    PubMed Central

    Michels, Ingo Ilja; Stöver, Heino; Gerlach, Ralf

    2007-01-01

    Background After a long and controversial debate methadone maintenance treatment (MMT) was first introduced in Germany in 1987. The number of patients in MMT – first low because of strict admission criteria – increased considerably since the 1990s up to some 65,000 at the end of 2006. In Germany each general practitioner (GP), who has completed an additional training in addiction medicine, is allowed to prescribe substitution drugs to opioid dependent patients. Currently 2,700 GPs prescribe substitution drugs. Psychosocial care should be made available to all MMT patients. Results The results of research studies and practical experiences clearly indicate that patients benefit substantially from MMT with improvements in physical and psychological health. MMT proves successful in attaining high retention rates (65 % to 85 % in the first years, up to 50 % after more than seven years) and plays a major role in accessing and maintaining ongoing medical treatment for HIV and hepatitis. MMT is also seen as a vital factor in the process of social re-integration and it contributes to the reduction of drug related harms such as mortality and morbidity and to the prevention of infectious diseases. Some 10 % of MMT patients become drug-free in the long run. Methadone is the most commonly prescribed substitution medication in Germany, although buprenorphine is attaining rising importance. Access to MMT in rural areas is very patchy and still constitutes a problem. There are only few employment opportunities for patients participating in MMT, although regular employment is considered unanimously as a positive factor of treatment success. Substitution treatment in German prisons is heterogeneous in access and treatment modalities. Access is very patchy and the number of inmates in treatment is limited. Nevertheless, substitution treatment plays a substantial part in the health care system provided to drug users in Germany. Conclusion In Germany, a history of substitution

  14. Initiation of buprenorphine during incarceration and retention in treatment upon release.

    PubMed

    Zaller, Nickolas; McKenzie, Michelle; Friedmann, Peter D; Green, Traci C; McGowan, Samuel; Rich, Josiah D

    2013-08-01

    We report here on a feasibility study of initiating buprenorphine/naloxone prior to release from incarceration and linking participants to community treatment providers upon release. The study consisted of a small number of Rhode Island (RI) prisoners (N = 44) diagnosed with opioid dependence. The study design is a single arm, open-label pilot study with a 6-month follow up interview conducted in the community. However, a natural experiment arose during the study comparing pre-release initiation of buprenorphone/naloxone to initiation post-release. Time to post-release prescriber appointment (mean days) for initiation of treatment outside Rhode Island Department of Corrections (RIDOC) versus inside RIDOC was 8.8 and 3.9, respectively (p = .1). Median post release treatment duration (weeks) for outside RIDOC versus inside RIDOC was 9 and 24, respectively (p = .007). We conclude that initiating buprenorphine/naloxone prior to release from incarceration may increase engagement and retention in community-based treatment. PMID:23541303

  15. Two-year Experience with Buprenorphine-naloxone (Suboxone) for Maintenance Treatment of Opioid Dependence Within a Private Practice Setting.

    PubMed

    Finch, James W; Kamien, Jonathan B; Amass, Leslie

    2007-06-01

    Office-based buprenorphine-naloxone (Suboxone) treatment in the United States has significantly improved access to safe and effective opioid-dependence therapy. Little data from physicians' experiences prescribing Suboxone in private offices have been available. This retrospective chart review describes a family practitioner's first 2 years of clinical experience prescribing Suboxone for opioid dependence to 71 patients in a private office. After directly observed rapid office dose induction, Suboxone prescriptions were given monthly after evidence of continued stability. Urine was screened regularly and patients were referred for counseling and other ancillary services. Patients averaged 32 years old, 4.3 years of opioid dependence, and were primarily white (93%) and employed (70%). Fifty-two percent used heroin primarily (most by injection), and 70% had no agonist substitution therapy history. Almost half (47%) paid for their own treatment. Compliance during dose induction was excellent. Suboxone maintenance doses averaged 10 (range, 2-24) mg per day. More than 80% of urine samples were opioid-negative after Suboxone treatment began, although urinalysis did not always include a test for oxycodone. Seventy-five percent had successful outcomes by remaining in Suboxone treatment (43%), tapering successfully (21%), transferring to methadone maintenance (7%), or inpatient treatment (4%). Fifty-eight percent reported receiving counseling. Almost all (85%) paid their fees on time. There were no safety, medication abuse, or diversion issues detected. Overall, office-based Suboxone therapy was easily implemented and the physician considered the experience excellent. Suboxone maintenance was associated with good treatment retention and significantly reduced opioid use, and it is helping to reach patients, including injection drug users, without histories of agonist substitution therapy. PMID:21768942

  16. Buprenorphine for opioid dependence

    PubMed Central

    Ling, Walter

    2014-01-01

    As a treatment agent for opioid dependence, buprenorphine is a nearly ideal medication at our current stage of medication development. Unlike methadone, buprenorphine dosage can be rapidly adjusted with minimal potential for inducing severe consequences. In addition to its intrinsic safety, buprenorphine's relatively low abuse liability in the combination product (i.e., with naloxone as Suboxone®) makes it even more acceptable in regulatory quarters as well as to prescribing physicians. The approval of buprenorphine as a pharmacotherapy for opioid dependence returns to physicians the ability to treat their opioid-dependent patients with an effective opioid-based treatment for the first time in nearly 100 years. Buprenorphine is an opioid, however, and potential for misuse remains, even in combination with naloxone. Whether buprenorphine will be increasingly accepted as a treatment for opioid-dependent patients depends on clinicians recognizing the advantages of its uniquely useful properties while still heeding the need to manage their patients' therapy with reasonable vigilance. PMID:19402772

  17. Unusual false-positive case of urinary screening for buprenorphine.

    PubMed

    Lippi, Giuseppe; Romero, Araelsis; Cervellin, Gianfranco; Mercadanti, Mariella

    2011-01-01

    Buprenorphine is a centrally acting analgesic drug that is administered for the management of opioid dependence and as an analgesic drug for the treatment of chronic pain. The growing use of this substance has determined an increased need for laboratory testing for either detection and confirmation of the illicit use or monitoring compliance as a substitution therapy for opioid dependence. We describe here the case of urinary sample adulteration with exogenous buprenorphine (6,952 ng/ml), which has led to afalse-positive immunoassay test result (14.9 ng/ml) on a subsequent sample due to a phenomenon of instrumental carry-over. This unusual case confirms the importance to take into account adulteration when screening urines for buprenorphine in patients undergoing substitution therapy for opioid dependence, routinely perform a confirmation assay on positive samples, and rule out instrumental carry-over. PMID:21786326

  18. Buprenorphine for opioid addiction

    PubMed Central

    Ling, Walter; Mooney, Larissa; Torrington, Matthew

    2014-01-01

    SUMMARY Buprenorphine is a partial opioid agonist of the µ-receptor, and is used as a daily dose sublingual tablet or filmstrip for managing opioid addiction. In the USA, the Drug Addiction Treatment Act of 2000 made buprenorphine the only opioid medication for opioid addiction that can be prescribed in an office-based setting. Owing to its high affinity for the µ-receptor, buprenorphine inhibits the reinforcing effect of exogenous opioids. The ceiling effect of buprenorphine's µ-agonist activity reduces the potential for drug overdose and confers low toxicity even at high doses. Buprenorphine pharmacotherapy has proven to be a treatment approach that supports recovery from addiction while reducing or curtailing the use of opioids. This article examines buprenorphine pharmacotherapy for opioid addiction, focusing on the situation in the USA, and is based on a review of pertinent literature, and the authors’ research and clinical experience. The references in this paper were chosen according to the authors’ judgment of quality and relevance, and with respect to their familiarity and involvement in related research. PMID:24654720

  19. Supply of Buprenorphine Waivered Physicians: The Influence of State Policies

    PubMed Central

    Stein, Bradley D.; Gordon, Adam J.; Dick, Andrew W.; Burns, Rachel M.; Pacula, Rosalie Liccardo; Farmer, Carrie M.; Leslie, Douglas L.; Sorbero, Mark

    2015-01-01

    Buprenorphine, an effective opioid use disorder treatment, can be prescribed only by buprenorphine-waivered physicians. We calculated the number of buprenorphine-waivered physicians/100,000 county residents using 2008–11 Buprenorphine Waiver Notification System data, and used multivariate regression models to predict number of buprenorphine-waivered physicians/100,000 residents in a county as a function of county characteristics, state policies and efforts to promote buprenorphine use. In 2011, 43% of US counties had no buprenorphine-waivered physicians and 7% had 20 or more waivered physicians. Medicaid funding, opioid overdose deaths, and specific state guidance for office-based buprenorphine use were associated with more buprenorphine-waivered physicians, while encouraging methadone programs to promote buprenorphine use had no impact. Our findings provide important empirical information to individuals seeking to identify effective approaches to increase the number of physicians able to prescribe buprenorphine. PMID:25218919

  20. Predictors of Abstinence: National Institute of Drug Abuse Multisite Buprenorphine/Naloxone Treatment Trial in Opioid-Dependent Youth

    ERIC Educational Resources Information Center

    Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

    2011-01-01

    Objective: To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth. Method: Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly…

  1. Facts about Buprenorphine for Treatment of Opioid Addiction

    MedlinePlus

    ... Families and Friends (SMA) 09-4443 • Introduction to Methadone (SMA) 06-4123 • Faces of Change: An Illustrated Booklet for Consumers (SMA) 08-4174 • What Is Substance Abuse Treatment? A Booklet for Families (SMA) 08-4126 (also ...

  2. Combined Abuse of Clonidine and Amitriptyline in a Patient on Buprenorphine Maintenance Treatment

    PubMed Central

    Dittmer, Trent; Sigman, Erika J.; Clemons, Holly; Johnson, J. Aaron

    2014-01-01

    Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed. PMID:25314340

  3. Determination of buprenorphine, norbuprenorphine and naloxone in fingernail clippings and urine of patients under opioid substitution therapy.

    PubMed

    Tzatzarakis, Manolis N; Vakonaki, Elena; Kovatsi, Leda; Belivanis, Stamatis; Mantsi, Mary; Alegakis, Athanasios; Liesivuori, Jyrki; Tsatsakis, Aristidis M

    2015-05-01

    The aim of this study was to develop and validate a method for the determination of buprenorphine (BUP), norbuprenorphine (NBUP) and naloxone (NAL) in fingernails and urine samples collected from former heroin users under suboxone substitution therapy. The analytes were extracted by solid-liquid or solid-phase extraction and were analyzed by liquid chromatography-mass spectrometry. The validation of the analytical methods developed included linearity, recovery, accuracy, precision, ion suppression, sensitivity of interfaces and limits of determination and quantification. The validated methods were applied to samples from 46 individuals. The majority of the urine samples were positive for all analytes (93.5% for BUP, 95.7% for NBUP and 84.8% for NAL). In nails, a higher detection rate was observed for NBUP and BUP (89.1%), compared with NAL (10.9%). The median values of the NBUP/BUP and the NAL/BUP ratio were 2.5 and 0.3 in urine and 0.8 and 0.3 in nails, respectively. A statistically significant correlation was found between the BUP, NBUP and total BUP (BUP and NBUP) concentrations in urine and those in nails. A weak correlation was observed between the daily dose (mg/day) and total BUP (P = 0.069), or NBUP (P = 0.072) concentrations in urine. In contrast, a strong correlation was found between the total amount of BUP administered during the last 12 months and total BUP (P = 0.038), or NBUP (P = 0.023) concentrations in urine. Moreover urine BUP, NBUP and total BUP concentrations correlated significantly. Our study demonstrated successfully the application of the developed method for the determination of the three analytes in urine and nails. PMID:25663675

  4. Craving and subsequent opioid use among opioid dependent patients who initiate treatment with buprenorphine

    PubMed Central

    Tsui, Judith I.; Anderson, Bradley J.; Strong, David R.; Stein, Michael D.

    2016-01-01

    Background Few studies have directly assessed associations between craving and subsequent opioid use among treated patients. Our objective was to prospectively evaluate the relative utility of two craving questionnaires to predict opioid use among opioid dependent patients in treatment. Method Opioid dependent patients (n=147) initiating buprenorphine treatment were assessed for three months. Craving was measured using: 1) the Desires for Drug Questionnaire (DDQ) and 2) the Penn Alcohol-Craving Scale adapted for opioid craving (PCS) for this study. Multi-level logistic regression models estimated the effects of craving on the likelihood of opioid use after adjusting for gender, age, ethnicity, education, opioid of choice, frequency of use, pain and depression. In these analyses craving assessed at time t was entered as a time-varying predictor of opioid use at time t+1. Results In adjusted regression models, a 1-point increase in PCS scores (on a 7-point scale) was associated with a significant increase in the odds of opioid use at the subsequent assessment (OR = 1.27, 95% CI 1.08; 1.49, p < .01). The odds of opioid use at the subsequent follow-up assessment increased significantly as DDQ desire and intention scores increased (OR = 1.25, 95%CI 1.03; 1.51, p< .05), but was not associated significantly with DDQ negative reinforcement (OR = 1.01, 95%CI 0.88; 1.17, p > .05) or DDQ control (OR = 0.97, 95%CI 0.85; 1.11, p > .05) scores. Conclusion Self-reported craving for opioids was associated with subsequent lapse to opioid use among a cohort of patients treated with buprenorphine. PMID:24521036

  5. Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European American females

    PubMed Central

    Clarke, Toni-Kim; Crist, Richard C.; Ang, Alfonso; Ambrose-Lanci, Lisa M.; Lohoff, Falk W.; Saxon, Andrew J.; Ling, Walter; Hillhouse, Maureen P.; Bruce, R. Douglas; Woody, George; Berrettini, Wade H.

    2013-01-01

    Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. While these drugs show some efficacy in treating opioid dependence, treatment response varies among individuals. It is likely that genetic factors play a role in determining treatment outcome. This study analyses the pharmacogenetic association of 6 polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone ((Suboxone®) over the course of a 24 week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid positive urine drug screens over the 24 weeks. In the total sample, no SNPs in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed 2 intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (p=0.03, RR=1.67, 95% C.I.[1.06-2.1]). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (p=0.006, RR=2.15, 95%C.I.[1.3-2.29]). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be useful when considering treatment options for female opioid addicts, however confirmation in an independent sample is warranted. PMID:24126707

  6. Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European-American females.

    PubMed

    Clarke, T-K; Crist, R C; Ang, A; Ambrose-Lanci, L M; Lohoff, F W; Saxon, A J; Ling, W; Hillhouse, M P; Bruce, R D; Woody, G; Berrettini, W H

    2014-06-01

    Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. Although these drugs show some efficacy in treating opioid dependence, treatment response varies among individuals. It is likely that genetic factors have a role in determining treatment outcome. This study analyses the pharmacogenetic association of six polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone (Suboxone) over the course of a 24-week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid-positive urine drug screens over the 24 weeks. In the total sample, no single-nucleotide polymorphisms (SNPs) in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed two intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (P=0.03, relative risk (RR)=1.67, 95% confidence interval (CI) 1.06-2.1). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (P=0.006, RR=2.15, 95% CI 1.3-2.29). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be useful when considering treatment options for female opioid addicts, however, confirmation in an independent sample is warranted. PMID:24126707

  7. Case series of buprenorphine injectors in Kuala Lumpur, Malaysia.

    PubMed

    Bruce, R Douglas; Govindasamy, Sumathi; Sylla, Laurie; Haddad, Marwan S; Kamarulzaman, Adeeba; Altice, Frederick L

    2008-01-01

    Diversion of buprenorphine has been described in settings where it is legally prescribed and has become an increasing concern in Malaysia; it resulted in banning of buprenorphine in Singapore where unsubstantiated case reports suggested that buprenorphine injection was associated with particularly poor outcomes. We therefore conducted a case series of qualitative interviews with buprenorphine injectors in Kuala Lumpur, Malaysia to examine further the issues surrounding buprenorphine injection as well as the abuse of midazolam in combination with buprenorphine. Interviews with 19 men do not suggest significant adverse health consequences from buprenorphine injection alone and injectors have adapted diverted buprenorphine as a treatment modality. A subset of these injectors, however, combined buprenorphine and midazolam for euphoric effects with resultant symptoms of a possible pharmacological interaction. Prospective cohort studies, rather than hospital-derived samples, are needed to better understand the safety of buprenorphine injection. PMID:18584580

  8. Correlates of Nine-Month Retention following Interim Buprenorphine-Naloxone Treatment in Opioid Dependence: A Pilot Study

    PubMed Central

    Håkansson, A.; Widinghoff, C.; Abrahamsson, T.; Gedeon, C.

    2016-01-01

    Interim medication-only treatment has been suggested for the initiation of opioid maintenance treatment (OMT) in opioid-dependent subjects, but this rarely has been studied using buprenorphine instead of methadone. Following a pilot trial assessing interim buprenorphine-naloxone treatment in order to facilitate transfer into OMT, we here aimed to study retention, and potential correlates of retention, in full-scale treatment. Thirty-six patients successfully referred from a waiting list through an interim treatment phase were followed for nine months in OMT. Baseline characteristics, as well as urine analyses during the interim phase and during full-scale OMT, were studied as potential correlates of retention. The nine-month retention in OMT was 83 percent (n = 30). While interim-phase urine samples positive for benzodiazepines did not significantly predict dropout from full-scale OMT (p = 0.09), urine samples positive for benzodiazepines within full-scale OMT were significantly associated with dropout (p < 0.01), in contrast to other substances and baseline characteristics. Retention remained high through nine months in this pilot study sample of patients referred through buprenorphine-naloxone interim treatment, but use of benzodiazepines is problematic, and the present data suggest that it may be associated with treatment dropout. PMID:26904355

  9. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

    PubMed Central

    Chen, Hwei-Hsien; Chiang, Yao-Chang; Yuan, Zung Fan; Kuo, Chung-Chih; Lai, Mei-Dan; Hung, Tsai-Wei; Ho, Ing-kang; Chen, Shao-Tsu

    2015-01-01

    Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3–20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light–dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light–dark transition in both male and female offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders. PMID:25834439

  10. Buprenorphine versus methadone for opioid dependence: predictor variables for treatment outcome.

    PubMed

    Gerra, G; Borella, F; Zaimovic, A; Moi, G; Bussandri, M; Bubici, C; Bertacca, S

    2004-07-15

    The present study compared in a clinical non-experimental setting the efficacy of buprenorphine (BUP) and methadone (METH) in the treatment of opioid dependence: all the subjects included in the study showed severe long-lasting heroin addiction. Participants (154) were applicants to a 12 weeks treatment program, who were assigned to either METH (78) (mean doses 81.5 +/- 36.4 mg) or BUP (76) (mean doses 9.2 +/- 3.4 mg) treatment. Aim of the study was to evaluate patient/treatment variables possibly influencing retention rate, abstinence from illicit drugs and mood changes. METH patients showed a higher retention rate at week 4 (78.2 versus 65.8) (P < 0.05), but BUP and METH were equally effective in sustaining retention in treatment and compliance with medication at week 12 (61.5 versus 59.2). Retention rate was influenced by dose, psychosocial functioning and not by psychiatric comorbidity in METH patients. In contrast, BUP maintained patients who completed the observational period showed a significantly higher rate of depression than those who dropped out (P < 0.01) and the intention to treat sample (P < 0.05). No relationship between retention and dose, or retention and psychosocial functioning was evidenced for BUP patients. The risk of positive urine testing was similar between METH and BUP, as expression of illicit drug use in general. At week 12, the patients treated with METH showed more risk of illicit opioid use than those treated with BUP (32.1% versus 25.6%) (P < 0.05). Negative urines were associated with higher doses in both METH and BUP patients. As evidenced for retention, substance abuse history and psychosocial functioning appear unable to influence urinalyses results in BUP patients. Buprenorphine maintained patients who showed negative urines presented a significantly higher rate of depression than those with positive urines (P < 0.05). Alternatively, psychiatric comorbidity was found unrelated to urinalyses results in METH patients. Our data

  11. Opioid addiction and abuse in primary care practice: a comparison of methadone and buprenorphine as treatment options.

    PubMed

    Bonhomme, Jean; Shim, Ruth S; Gooden, Richard; Tyus, Dawn; Rust, George

    2012-01-01

    Opioid abuse and addiction have increased in frequency in the United States over the past 20 years. In 2009, an estimated 5.3 million persons used opioid medications nonmedically within the past month, 200000 used heroin, and approximately 9.6% of African Americans used an illicit drug. Racial and ethnic minorities experience disparities in availability and access to mental health care, including substance use disorders. Primary care practitioners are often called upon to differentiate between appropriate, medically indicated opioid use in pain management vs inappropriate abuse or addiction. Racial and ethnic minority populations tend to favor primary care treatment settings over specialty mental health settings. Recent therapeutic advances allow patients requiring specialized treatment for opioid abuse and addiction to be managed in primary care settings. The Drug Addiction Treatment Act of 2000 enables qualified physicians with readily available short-term training to treat opioid-dependent patients with buprenorphine in an office-based setting, potentially making primary care physicians active partners in the diagnosis and treatment of opioid use disorders. Methadone and buprenorphine are effective opioid replacement agents for maintenance and/or detoxification of opioid-addicted individuals. However, restrictive federal regulations and stigmatization of opioid addiction and treatment have limited the availability of methadone. The opioid partial agonist-antagonist buprenorphine/naloxone combination has proven an effective alternative. This article reviews the literature on differences between buprenorphine and methadone regarding availability, efficacy, safety, side-effects, and dosing, identifying resources for enhancing the effectiveness of medication-assisted recovery through coordination with behavioral/psychological counseling, embedded in the context of recovery-oriented systems of care. PMID:23092049

  12. Predictors of Abstinence: NIDA Multi-site Buprenorphine/Naloxone Treatment Trial in Opioid Dependent Youth

    PubMed Central

    Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

    2013-01-01

    Objective To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal) assisted psychosocial treatment for opioid dependent youth Method Secondary analyses of data from 152 youth (ages 15–21) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification, both with weekly individual and group drug counseling. Logistic regression models were constructed to identify baseline and during-treatment predictors of opioid positive urines (OPU) at week-12. Predictors were selected based on significance or trend toward significance (i.e. p<0.1) and backward stepwise selection was used, controlling for treatment group, to produce final independent predictors at p ≤ 0.05. Results Youth presenting to treatment with past 30-day injection drug use (IDU) and more active medical/psychiatric problems were less likely to have a week-12 OPU. Those with early treatment opioid abstinence (i.e. weeks 1 and 2); and those who received additional non-study treatments during the study were less likely to have a week-12 OPU; and those not completing 12 weeks of treatment were more likely to have an OPU. Conclusions Youth with advanced illness (i.e. reporting IDU and additional health problems), and those receiving ancillary treatments to augment study treatment were more likely to have lower opioid use. Treatment success in the first 2 weeks and completion of 12 weeks of treatment were associated with lower rates of OPU. These findings suggest that youth with advanced illness respond well to Bup/Nal treatment, and identify options for tailoring treatment for opioid-dependent youth presenting at community-based settings. PMID:22024000

  13. Preference for brand-name buprenorphine is related to severity of addiction among outpatients in opioid maintenance treatment.

    PubMed

    Binder, Philippe; Messaadi, Nassir; Perault-Pochat, Marie-Christine; Gagey, Stéphanie; Brabant, Yann; Ingrand, Pierre

    2016-01-01

    As a form of opioid maintenance treatment, high-dose buprenorphine is increasingly being used in the United States. On the French market since 1996, it is the most commonly prescribed and frequently employed opioid maintenance treatment. For unknown reasons, the brand-name form is used far more often than the generic form (76-24%). The objective was to show that the patients' levels of addiction were differentiated according to the form of buprenorphine currently being used and to their previous experience of a different form. An observational study in 9 sites throughout France used self-assessment questionnaires filled out in retail pharmacies by all patients to whom their prescribed buprenorphine treatment was being delivered. The 151 canvassed pharmacies solicited 879 patients, of whom 724 completed the questionnaires. Participants were statistically similar to non-participants. The patients using the brand-name form subsequent to experience with the generic form exhibited a more elevated addiction severity index and a higher dosage than brand-name form users with no experience of a different form. Compared to generic users, their doses were higher, their was addiction more severe, and their alcohol consumption was more excessive; they were also more likely to make daily use of psychotropic substances. However, the level of misuse or illicit consumption was similar between these groups. Preferring the brand-name buprenorphine form to the generic form is associated with a higher level of severe addiction, a more frequent need for daily psychotropics, and excessive drinking; but the study was unable to show a causal link. PMID:26745033

  14. Patient Perspectives on Buprenorphine/Naloxone: A Qualitative Study of Retention During the Starting Treatment with Agonist Replacement Therapies (START) Study

    PubMed Central

    Teruya, Cheryl; Schwartz, Robert P.; Mitchell, Shannon Gwin; Hasson, Albert L.; Thomas, Christie; Buoncristiani, Samantha H.; Hser, Yih-Ing; Wiest, Katharina; Cohen, Allan J.; Glick, Naomi; Jacobs, Petra; McLaughlin, Paul; Ling, Walter

    2014-01-01

    This study examines the barriers and facilitators of retention among patients receiving buprenorphine/naloxone at eight community-based opioid treatment programs across the United States. Participants (n=105) were recruited up to three-and-a-half years after having participated in a randomized clinical trial comparing the effect of buprenorphine/naloxone and methadone on liver function. Semi-structured interviews were conducted with 67 patients provided with buprenorphine/naloxone who had terminated early and 38 patients who had completed at least 24 weeks of the trial. Qualitative data were analyzed using the constant comparison method. Barriers to buprenorphine/naloxone retention that emerged included factors associated with: (1) the design of the clinical trial, (2) negative medication or treatment experience, and (3) personal circumstances. The facilitators comprised: (1) positive experience with the medication, (2) personal determination and commitment to complete, and (3) staff encouragement and support. The themes drawn from interviews highlight the importance of considering patients’ prior experience with buprenorphine/naloxone and methadone, medication preference, personal circumstances, and motivation to abstain from illicit use or misuse of opioids, as these may influence retention. Ongoing education of patients and staff regarding buprenorphine/naloxone, especially in comparison to methadone, and support from staff and peers are essential. PMID:25364994

  15. Shifting blame: Buprenorphine prescribers, addiction treatment, and prescription monitoring in middle-class America.

    PubMed

    Mendoza, Sonia; Rivera-Cabrero, Allyssa S; Hansen, Helena

    2016-08-01

    Growing nonmedical prescription opioid analgesic use among suburban and rural Whites has changed the public's perception of the nature of opioid addiction, and of appropriate interventions. Opioid addiction has been recast as a biological disorder in which patients are victims of their neurotransmitters and opioid prescribers are irresponsible purveyors of dangerous substances requiring controls. This framing has led to a different set of policy responses than the "War on Drugs" that has focused on heroin trade in poor urban communities; in response to prescription opioid addiction, prescription drug monitoring programs and tamper-resistant opioid formulations have arisen as primary interventions in place of law enforcement. Through the analysis of preliminary findings from interviews with physicians who are certified to manage opioid addiction with the opioid pharmaceutical buprenorphine, we argue that an increase in prescriber monitoring has shifted the focus from addicted people to prescribers as a threat, paradoxically driving users to illicit markets and constricting their access to pharmaceutical treatment for opioid addiction. Prescriber monitoring is also altering clinical cultures of care, as general physicians respond to heightened surveillance and the psychosocial complexities of treating addiction with either rejection of opioid dependent patients, or with resourceful attempts to create support systems for their treatment where none exists. PMID:27488225

  16. Improved buprenorphine immunoassay performance after urine treatment with β-glucuronidase.

    PubMed

    Snyder, Marion L; Darragh, Alicia; Flood, James G; Jones, Jenny; Ropar, Kaitlin; Jarolim, Petr; Melanson, Stacy E F

    2014-01-01

    Buprenorphine (BUP), a semi-synthetic opioid analgesic, is increasingly prescribed for the treatment of chronic pain and opioid dependence. Urine immunoassay screening methods are available for monitoring BUP compliance and misuse; however, these screens may have poor sensitivity or specificity. We evaluated whether the pretreatment of urine with β-glucuronidase (BG) improves the sensitivity and overall accuracy of three BUP enzyme immunoassays when compared with liquid chromatography-tandem mass spectrometry (LC-MS-MS). Urine samples sent to our laboratories for BUP testing (n = 114) were analyzed before and after BG pretreatment by cloned enzyme donor immunoassay (CEDIA), enzyme immunoassay (EIA) and homogenous EIA (HEIA) immunoassays using a common 5 ng/mL cutoff. Total BUP and norbuprenorphine (NBUP) concentrations were measured by LC-MS-MS as the reference method. Urine BG pretreatment improved EIA, HEIA and CEDIA sensitivities from 70, 82 and 94%, respectively, to 97% for each of the three methods, when compared with LC-MS-MS. While the specificity of the EIA and HEIA remained 100% after BG pretreatment, the specificity of the CEDIA decreased from 74 to 67%. Urine pretreatment with BG is recommended to improve sensitivity of the EIA and HEIA BUP screening methods. PMID:24802159

  17. The association between cocaine use and treatment outcomes in patients receiving office-based buprenorphine/naloxone for the treatment of opioid dependence.

    PubMed

    Sullivan, Lynn E; Moore, Brent A; O'Connor, Patrick G; Barry, Declan T; Chawarski, Marek C; Schottenfeld, Richard S; Fiellin, David A

    2010-01-01

    Cocaine use in patients receiving methadone is associated with worse treatment outcomes. The association between cocaine use and office-based buprenorphine/naloxone treatment outcomes is not known. We evaluated the association between baseline and in-treatment cocaine use, treatment retention, and urine toxicology results in 162 patients enrolled in a 24-week trial of primary care office-based buprenorphine/naloxone maintenance. Patients with baseline cocaine metabolite-negative urine toxicology tests compared with those with cocaine metabolite-positive tests had more mean weeks of treatment retention (18.3 vs. 15.8, p = .04), a greater percentage completed 24 weeks of treatment (50% vs. 33%, p = .04) and had a greater percentage of opioid-negative urines (47% vs. 34%, p = .02). Patients with in-treatment cocaine metabolite-negative urine toxicology tests compared with cocaine metabolite-positive patients had more mean weeks of treatment retention (19.0 vs. 16.5, p = .003), a greater percentage completed 24 weeks of treatment (60% vs. 30%, p < .001), and had a greater percentage of opioid-negative urines (51% vs. 35%, p = .001). We conclude that both baseline and in-treatment cocaine use is associated with worse treatment outcomes in patients receiving office-based buprenorphine/naloxone and may benefit from targeted interventions. PMID:20132122

  18. Buprenorphine is protective against the depressive effects of norbuprenorphine on ventilation

    SciTech Connect

    Megarbane, Bruno . E-mail: bruno-megarbane@wanadoo.fr; Marie, Nicolas; Pirnay, Stephane; Borron, Stephen W.; Gueye, Papa N.; Risede, Patricia; Monier, Claire; Noble, Florence; Baud, Frederic J.

    2006-05-01

    High dose buprenorphine is used as substitution treatment in heroin addiction. However, deaths have been reported in addicts using buprenorphine. The role of norbuprenorphine, an N-dealkyl metabolite of buprenorphine, was hypothesized to explain these fatal cases. We determined the median intravenous lethal dose (LD{sub 5}) of norbuprenorphine in male Sprague-Dawley rats. The effects of a single intravenous dose of 3 or 9 mg/kg norbuprenorphine alone on arterial blood gases were studied. Finally, the effect of pre- and post-administrations of buprenorphine on norbuprenorphine-induced changes on arterial blood gases were analyzed. Norbuprenorphine's LD{sub 5} was 10 mg kg{sup -1}. Norbuprenorphine 3 mg kg{sup -1} produces the rapid onset of sustained respiratory depression, as demonstrated at 20 min by a maximal significant increase in PaCO{sub 2} (8.4 {+-} 0.9 versus 5.7 {+-} 0.1 kPa), decrease in arterial pH (7.25 {+-} 0.06 versus 7.44 {+-} 0.01), and hypoxia (8.3 {+-} 0.6 versus 11.1 {+-} 0.2 kPa). Buprenorphine not only protected against the effects of 3 mg kg{sup -1} norbuprenorphine in a dose-dependent manner but also reversed the effects when given afterward. Binding experiments suggest a role for mu- and to a lesser extent for delta-opioid receptors in buprenorphine protective effect against norbuprenorphine-induced respiratory depression. In conclusion, our data clearly show that norbuprenorphine alone causes important deleterious effects on ventilation in rats. However, buprenorphine protective effect calls into question the role for norbuprenorphine in respiratory toxicity associated with buprenorphine use.

  19. “The chief of the services is very enthusiastic about it”: A qualitative study of the adoption of buprenorphine for opioid addiction treatment

    PubMed Central

    Green, Carla A.; McCarty, Dennis; Mertens, Jennifer; Lynch, Frances L.; Hilde, Anadam; Firemark, Alison; Weisner, Constance M.; Pating, David; Anderson, Bradley M.

    2013-01-01

    Qualified physicians may prescribe buprenorphine to treat opioid dependence, but medication use remains controversial. We examined adoption of buprenorphine in two not-for-profit integrated health plans, over time, completing 101 semi-structured interviews with clinicians and clinician-administrators from primary and specialty care. Transcripts were reviewed, coded, and analyzed. A strong leader championing the new treatment was critical for adoption in both health plans. Once clinicians began using buprenorphine, patients’ and other clinicians’ experiences affected decisions more than did the champion. With experience, protocols developed to manage unsuccessful patients and changed to support maintenance rather than detoxification. Diffusion outside addiction and mental health settings was nonexistent; primary care clinicians cited scope-of-practice issues and referred patients to specialty care. With greater diffusion came questions about long-term use and safety. Recognizing how implementation processes develop may suggest where, when, and how to best expend resources to increase adoption of such treatments. PMID:24268947

  20. Improved Quality of Life for Opioid Dependent Patients Receiving Buprenorphine Treatment in HIV Clinics

    PubMed Central

    Korthuis, P. Todd; Tozzi, Mary Jo; Nandi, Vijay; Fiellin, David A.; Weiss, Linda; Egan, James E.; Botsko, Michael; Acosta, Angela; Gourevitch, Marc N.; Hersh, David; Hsu, Jeffrey; Boverman, Joshua; Altice, Frederick L.

    2011-01-01

    Background Opioid dependence and HIV infection are associated with poor health-related quality of life (HRQOL). Buprenorphine/naloxone (bup/nx) provided in HIV care settings may improve HRQOL. Methods We surveyed 289 HIV-infected opioid-dependent persons treated with clinic-based bup/nx about HRQOL using the Short Form Health Survey (SF-12) administered at baseline, 3, 6, 9, and 12 months. We used normalized SF-12 scores which correspond to a mean HRQOL of 50 for the general U.S. population (SD 10, possible range 0–100). We compared mean normalized mental and physical composite and component scores in quarters 1, 2, 3, and 4 with baseline scores using GEE models. We assessed the effect of clinic-based bup/nx prescription on HRQOL composite scores using mixed effects regression with site as random effect and time as repeated effect. Results Baseline normalized SF-12 scores were lower than the general U.S. population for all HRQOL domains. Average composite mental HRQOL improved from 38.3 (SE 12.5) to 43.4 (SE 13.2) (β 1.13 [95% CI 0.72, 1.54]) and composite physical HRQOL remained unchanged (β 0.21 [95% CI −0.16, 0.57]) over 12 months follow-up. Continued bup/nx treatment across all four quarters was associated with improvements in both physical (β 2.38 [95% CI 0.63, 4.12]) and mental (β 2.51 [95% CI 0.42, 4.60]) HRQOL after adjusting for other contributors to HRQOL. Conclusions Clinic-based bup/nx maintenance therapy is potentially effective in ameliorating some of the adverse effects of opioid dependence on HRQOL for HIV-infected populations. PMID:21317593

  1. Buprenorphine therapy: an increasing challenge in oral and maxillofacial surgery.

    PubMed

    Wasson, Michael; Beirne, O Ross

    2013-08-01

    Suboxone is a 4:1 mixture of buprenorphine and naloxone and Subutex is buprenorphine alone. The high affinity μ-receptor binding of buprenorphine (Suboxone and Subutex) renders other opioids ineffective. Inadequate procedural sedation, inadequate analgesia, and significant drug interactions complicate the treatment of patients taking Suboxone or Subutex. Careful planning and an understanding of buprenorphine pharmacology can minimize potential perioperative complications in patients taking Suboxone or Subutex. PMID:23849373

  2. The BHIVES collaborative: organization and evaluation of a multisite demonstration of integrated buprenorphine/naloxone and HIV treatment.

    PubMed

    Weiss, Linda; Egan, James E; Botsko, Michael; Netherland, Julie; Fiellin, David A; Finkelstein, Ruth

    2011-03-01

    Substance abuse is associated with poor medical and quality-of-life outcomes among HIV-infected individuals. Although drug treatment may reduce these negative consequences, for many patients, options are limited. Buprenorphine/naloxone, an opioid agonist treatment that can be prescribed in the United States in office-based settings, can be used to expand treatment capacity and integrate substance abuse services into HIV care. Recognizing this potential, the US Health Resources and Services Administration funded the development and implementation of demonstration projects that integrated HIV care and buprenorphine/naloxone treatment at 10 sites across the country. An Evaluation and Technical Assistance Center provided programmatic and clinical support as well as oversight for an evaluation that examined the processes for and outcomes of integrated care. The evaluation included patient-level self-report and chart abstractions as well as provider and site level data collected through surveys and in-depth interviews. Although multisite demonstrations pose implementation and evaluation challenges, our experience demonstrates that these can, in part, be addressed through ongoing communication and technical assistance as well as a comprehensive evaluation design that incorporates multiple research methods and data sources. Although limitations to evaluation findings persist, they may be balanced by the scope and "real-world" context of the initiative. PMID:21317598

  3. Use of conventional, complementary, and alternative treatments for pain among individuals seeking primary care treatment with buprenorphine-naloxone

    PubMed Central

    Barry, Declan T.; Savant, Jonathan D.; Beitel, Mark; Cutter, Christopher J.; Moore, Brent A.; Schottenfeld, Richard S.; Fiellin, David A.

    2012-01-01

    Previous studies have not examined patterns of pain treatment use among patients seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence. Objectives To examine, among individuals with pain seeking BNT for opioid dependence, the use of pain treatment modalities, perceived efficacy of prior pain treatment, and interest in pursuing pain treatment while in BNT. Methods 244 patients seeking office-based BNT for opioid dependence completed measures of demographics, pain status (i.e. “chronic pain (CP)” [pain lasting at least 3 months] vs. “some pain (SP)” [pain in the past week not meeting the duration criteria for chronic pain]), pain treatment use, perceived efficacy of prior pain treatment, and interest in receiving pain treatment while in BNT. Results In comparison to the SP group (N = 87), the CP group (N = 88) was more likely to report past-week medical use of opioid medication (AOR 3.2, 95% CI 1.2–8.4), lifetime medical use of non-opioid prescribed medication (AOR 2.2, 95% CI 1.1–4.7), and lifetime use of prayer (AOR 2.8, 95% CI 1.2–6.5), and was less likely to report lifetime use of yoga (AOR 0.2, 95% CI 0.1–0.7) to treat pain. While the two pain groups did not differ on levels of perceived efficacy of prior lifetime pain treatments, in comparison to the SP group, the CP group was more likely to report interest in receiving pain treatment while in BNT (P < 0.001). Conclusions Individuals with pain seeking BNT for opioid dependence report a wide range of conventional, complementary, and alternative pain-related treatments and are interested (especially those with CP) in receiving pain management services along with BNT. PMID:23041680

  4. Office-Based Opioid Treatment with Buprenorphine (OBOT-B): Statewide Implementation of the Massachusetts Collaborative Care Model in Community Health Centers.

    PubMed

    LaBelle, Colleen T; Han, Steve Choongheon; Bergeron, Alexis; Samet, Jeffrey H

    2016-01-01

    We describe a Massachusetts Bureau of Substance Abuse Services' (BSAS) initiative to disseminate the office-based opioid treatment with buprenorphine (OBOT-B) Massachusetts Model from its development at Boston Medical Center (BMC) to its implementation at fourteen community health centers (CHCs) beginning in 2007. The Massachusetts Collaborative Care Model for the delivery of opioid agonist therapy with buprenorphine, in which nurses working with physicians play a central role in the evaluation and monitoring of patients, holds promise for the effective expansion of treatment for opioid use disorders. The training of and technical assistance for the OBOT nurses as well as a limited program assessment are described. Data spanning 6years (2007-2013) report patient demographics, prior treatment for opioid use disorders, history of overdose, housing, and employment. The expansion of OBOT to the fourteen CHCs increased the number of physicians who were "waivered" (i.e., enabling their prescribing of buprenorphine) by 375%, from 24 to 114, within 3years. During this period the annual admissions of OBOT patients to CHCs markedly increased. Dissemination of the Massachusetts Model of the Office-Based Opioid Treatment with Buprenorphine employing a collaborative care model with a central role for nursing enabled implementation of effective treatment for patients with an opioid use disorder at community health centers throughout Massachusetts while effectively engaging primary care physicians in this endeavor. PMID:26233698

  5. Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain

    PubMed Central

    Skaer, Tracy L

    2014-01-01

    Opioids continue to be first-line pharmacotherapy for patients suffering from cancer pain. Unfortunately, subtherapeutic dosage prescribing of pain medications remains common, and many cancer patients continue to suffer and experience diminished quality of life. A large variety of therapeutic options are available for cancer pain patients. Analgesic pharmacotherapy is based on the patient’s self-report of pain intensity and should be tailored to meet the requirements of each individual. Most, if not all, cancer pain patients will ultimately require modifications in their opioid pharmacotherapy. When changes in a patient’s medication regimen are needed, adequate pain control is best maintained through appropriate dosage conversion, scheduling immediate release medication for withdrawal prevention, and providing as needed dosing for breakthrough pain. Transdermal opioids are noninvasive, cause less constipation and sedation when compared to oral opioids, and may improve patient compliance. A relative potency of 100:1 is recommended when converting the patient from oral morphine to transdermal fentanyl. Based on the limited data available, there is significant interpatient variability with transdermal buprenorphine and equipotency recommendations from oral morphine of 75:1–110:1 have been suggested. Cancer patients may require larger transdermal buprenorphine doses to control their pain and may respond better to a more aggressive 75–100:1 potency ratio. This review outlines the prescribing of transdermal fentanyl and transdermal buprenorphine including how to safely and effectively convert to and use them for those with cancer pain. PMID:25170278

  6. Outcomes among buprenorphine-naloxone primary care patients after Hurricane Sandy

    PubMed Central

    2014-01-01

    -reported substance use were reported despite many disruptions to regular buprenorphine supplies and previous daily doses. Informal supplies of substitute buprenorphine from family and friends was common. Remote telephone refill support and a temporary back-up location that provided written prescription refills and medication dispensing for uninsured patients enabled some patients to maintain an adequate medication supply. Such adaptive strategies to ensure medication maintenance continuity pre/post natural disasters likely minimize poor treatment outcomes. PMID:24467734

  7. Patients more likely to engage in treatment at 30 days when given buprenorphine in the ED, referred for follow-up.

    PubMed

    2015-08-01

    A new randomized trial shows patients who present to the ED with opioid dependence are much more likely to engage in treatment when they receive buprenorphine along with coordinated follow-up than when they just receive a brief intervention and a facilitated referral for treatment or just screening and referral. However, barriers to prescribing are robust, and many ED leaders are not persuaded they should be in the business of providing treatment for addiction. In the trial, at 30 days 78% of patients in the buprenorphine group (89 of 114 patients) were engaged in addiction treatment, compared with just 45% of the patients in the brief intervention group (50 of 111 patients) and 37% of patients in the referral group (38 of 102 patients). To prescribe buprenorphine for addiction disease, providers must undergo training and pass a test to obtain a DEA waiver; they are limited to treating 100 patients. While experts note there are not enough providers to prescribe buprenorphine and provide the follow-up needed to patients with addiction disease, they also acknowledge concerns about drug diversion as well as potential problems with capacity if EDs take a larger role in treating addiction. PMID:26258203

  8. Long-term treatment with buprenorphine/naloxone in primary care: results at 2-5 years.

    PubMed

    Fiellin, David A; Moore, Brent A; Sullivan, Lynn E; Becker, William C; Pantalon, Michael V; Chawarski, Marek C; Barry, Declan T; O'Connor, Patrick G; Schottenfeld, Richard S

    2008-01-01

    To examine long-term outcomes with primary care office-based buprenorphine/naloxone treatment, we followed 53 opioid-dependent patients who had already demonstrated six months of documented clinical stability for 2-5 years. Primary outcomes were retention, illicit drug use, dose, satisfaction, serum transaminases, and adverse events. Thirty-eight percent of enrolled subjects were retained for two years. Ninety-one percent of urine samples had no evidence of opioid use, and patient satisfaction was high. Serum transaminases remained stable from baseline. No serious adverse events related to treatment occurred. We conclude that select opioid-dependent patients exhibit moderate levels of retention in primary care office-based treatment. PMID:18393054

  9. Improved HIV and substance abuse treatment outcomes for released HIV-infected prisoners: the impact of buprenorphine treatment.

    PubMed

    Springer, Sandra Ann; Chen, Shu; Altice, Frederick L

    2010-07-01

    HIV-infected prisoners fare poorly after release. Though rarely available, opioid agonist therapy (OAT) may be one way to improve HIV and substance abuse treatment outcomes after release. Of the 69 HIV-infected prisoners enrolled in a randomized controlled trial of directly administered antiretroviral therapy, 48 (70%) met DSM-IV criteria for opioid dependence. Of these, 30 (62.5%) selected OAT, either as methadone (N = 7, 14.5%) or buprenorphine/naloxone (BPN/NLX; N = 23, 48.0%). Twelve-week HIV and substance abuse treatment outcomes are reported as a sub-study for those selecting BPN/NLX. Retention was high: 21 (91%) completed BPN/NLX induction and 17 (74%) remained on BPN/NLX after 12 weeks. Compared with baseline, the proportion with a non-detectable viral load (61% vs 63% log(10) copies/mL) and mean CD4 count (367 vs 344 cells/mL) was unchanged at 12 weeks. Opiate-negative urine testing remained 83% for the 21 who completed induction. Using means from 10-point Likert scales, opioid craving was reduced from 6.0 to 1.8 within 3 days of BPN/NLX induction and satisfaction remained high at 9.5 throughout the 12 weeks. Adverse events were few and mild. BPN/NLX therapy was acceptable, safe and effective for both HIV and opioid treatment outcomes among released HIV-infected prisoners. Future randomized controlled trials are needed to affirm its benefit in this highly vulnerable population. PMID:20177974

  10. Lack of clinically significant drug interactions between nevirapine and buprenorphine.

    PubMed

    McCance-Katz, Elinore F; Moody, David E; Morse, Gene D; Ma, Qing; Rainey, Petrie M

    2010-01-01

    This study was conducted to determine whether drug interactions of clinical importance occur between buprenorphine, an opioid partial agonist medication used in treatment of opioid dependence, and the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine. Opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n = 7) participated in 24-hour sessions to determine the pharmacokinetics of buprenorphine alone and of buprenorphine and nevirapine following administration of 200 mg nevirapine daily for 15 days. Opiate withdrawal symptoms, cognitive effects, and adverse events were determined prior to and following nevirapine administration. Modest decreases were observed for AUC for buprenorphine and its metabolites. There was a trend for more rapid clearance of both buprenorphine (p = .08) and buprenorphine-3-glucuronide (p = .08). While no single effect reached statistical significance, the joint probability that the consistent declines in all measures of exposure were due to chance was extremely low, indicating that nevirapine significantly reduces overall exposure to buprenorphine and buprenorphine metabolites. Clinically significant consequences of the interaction were not observed. Buprenorphine did not alter nevirapine pharmacokinetics. Dose adjustments of either buprenorphine or nevirapine are not likely to be necessary when these drugs are coadministered for the treatment of opiate dependence and HIV disease. PMID:20132119

  11. Buprenorphine and buprenorphine/naloxone intoxication in children - how strong is the risk?

    PubMed

    Soyka, Michael

    2013-03-01

    Opioid maintenance therapy with methadone or buprenorphine is an established and first-line treatment for opioid dependence. Risk of diversion and toxicity of opioid prescription drugs, including buprenorphine, causes significant concerns. This is particularly the case in the United States, where the number of related emergency visits is increasing, especially in children. A systematic literature research (Medline, Pubmed) was performed to assess the risk associated with buprenorphine. The search, which was not limited to particular publication years, was performed with the key words buprenorphine AND toxicity (114 counts ) AND children (4 counts) and buprenorphine AND mortality AND children (5 counts). In addition, the author obtained information from relevant websites (NIDA, SAMSHA) and pharmacovigilance data from the manufacturer of buprenorphine. Clinical and toxicological data suggest a low risk for fatal intoxications associated with bupreorphine in adults. Data from emergency units indicate a dramatic, 20-fold increase in buprenorphine exposure in children over the past decade, mostly in those under 6. The US 'Researched Abuse, Diversion and Addiction-Related Surveillance' (RADARS) system indicates a lower risk of severe opioid intoxications with buprenorphine than with other opioids, with no fatal outcomes recorded. Correspondingly, data from spontaneous reports to the surveillance programme of the manufacturer of buprenorphine (13,600 buprenorphine exposures, 4879 of these in children under six) show a serious medical outcome in 34% of children under the age of six but only one fatal outcome. Although exposure to buprenorphine and other opioids remains a significant concern in children, the drug seems rather to be safe with respect to severe outcomes, in particular death. PMID:23489089

  12. Buprenorphine use in pregnant opioid users: a critical review.

    PubMed

    Soyka, Michael

    2013-08-01

    Pregnancy in opioid users poses a number of problems to treating physicians. Most guidelines recommend maintenance treatment to manage opioid addiction in pregnancy, with methadone being the gold standard. More recently, buprenorphine has been discussed as an alternate medication. The use and efficacy of buprenorphine in pregnancy is still controversial. This article reviews the current database on the basis of a detailed and critical literature search performed in MEDLINE (206 counts). Most of the relevant studies (randomised clinical trials and one national cohort sample) were published in the last 2 years and mainly compared buprenorphine with methadone. Some studies are related to maternal outcomes, others to foetal, neonatal or older child outcomes. With respect to maternal outcomes, most studies suggest that buprenorphine has similar effects to methadone. Very few data from small studies discuss an effect of buprenorphine on neurodevelopment of the foetus. Neonatal abstinence syndrome is common in infants of both buprenorphine- and methadone-maintained mothers. As regards neonatal outcomes, buprenorphine has the same clinical outcome as methadone, although some newer studies suggest that it causes fewer withdrawal symptoms. Since hardly any studies have investigated the combination of buprenorphine with naloxone (which has been suggested to possibly have teratogenic effects) in pregnant women, a switch to buprenorphine monotherapy is recommended in women who become pregnant while receiving the combination product. These novel findings indicate that buprenorphine is emerging as a first-line treatment for pregnant opioid users. PMID:23775478

  13. Emergency department visits and hospitalizations for buprenorphine ingestion by children--United States, 2010-2011.

    PubMed

    2013-01-25

    Buprenorphine (Subutex) and buprenorphine/naloxone (Suboxone) received Food and Drug Administration approval in 2002 for the treatment of opioid dependence. Introduction of these drugs expanded the availability of opioid-dependence treatment options to reduce the morbidity and mortality associated with opioid abuse, and buprenorphine has become an increasingly prescribed component of office-based treatment. However, unsupervised ingestion of buprenorphine-containing products by children is a growing concern. PMID:23344700

  14. Therapeutic switch to buprenorphine/naloxone from buprenorphine alone: clinical experience in an Italian addiction centre.

    PubMed

    Montesano, Franco; Zaccone, Domenico; Battaglia, Egidio; Genco, Felice; Mellace, Vincenzo

    2010-01-01

    of treatment effectiveness. Buprenorphine/naloxone can be administered in an outpatient or primary care setting, and effectively controls cravings and withdrawal symptoms. Patient satisfaction was high, making retention in treatment more likely. PMID:20450241

  15. Outcome of heroin-dependent adolescents presenting for opiate substitution treatment.

    PubMed

    Smyth, Bobby P; Fagan, John; Kernan, Kathy

    2012-01-01

    Because the outcome of methadone and buprenorphine substitution treatment in adolescents is unclear, we completed a retrospective cohort study of 100 consecutive heroin-dependent adolescents who sought these treatments over an 8-year recruitment period. The participants' average age was 16.6 years, and 54 were female. Half of the patient group remained in treatment for over 1 year. Among those still in treatment at 12 months, 39% demonstrated abstinence from heroin. The final route of departure from the treatment program was via planned detox for 22%, dropout for 32%, and imprisonment for 8%. The remaining 39% were transferred elsewhere for ongoing opiate substitution treatment after a median period of 23 months of treatment. Males were more likely to exit via imprisonment (p < .05), but other outcomes were not predicted by gender. There were no deaths during treatment among these 100 patients who had a cumulative period of 129 person years at risk. Our findings suggest that this treatment delivers reductions in heroin use and that one fifth of patients will exit treatment following detox completion within a 1- to 2-year time frame. PMID:21940134

  16. Training HIV Physicians to Prescribe Buprenorphine for Opioid Dependence

    ERIC Educational Resources Information Center

    Sullivan, Lynn E.; Tetrault, Jeanette; Bangalore, Deepa; Fiellin, David A.

    2006-01-01

    Few HIV physicians are trained to provide buprenorphine treatment. We conducted a cross-sectional survey to assess the impact of an eight-hour course on the treatment of opioid dependence on HIV physicians' preparedness to prescribe buprenorphine. One hundred thirteen of 257 trained physicians (44%) provided HIV care. Post-course, the majority of…

  17. Predictors of buprenorphine initial outpatient maintenance and dose taper response among non-treatment-seeking heroin dependent volunteers

    PubMed Central

    Woodcock, Eric A.; Lundahl, Leslie H.; Greenwald, Mark K.

    2014-01-01

    Background Buprenorphine (BUP) is effective for treating opioid use disorder. Individuals’ heroin-use characteristics may predict their responses to BUP, which could differ during maintenance and dose-taper phases. If so, treatment providers could use pre-treatment characteristics to personalize level of individual care and possibly improve treatment outcomes. Methods Non-treatment-seeking heroin-dependent volunteers (N=34) initiated outpatient BUP maintenance (8-mg/day) and submitted urine samples thrice weekly tested for opioids (non-contingent result). After completing three programmatically-related inpatient behavioral pharmacology experiments (while maintained on 8-mg/day BUP), participants were discharged and underwent a double-blind BUP dose taper (4-mg/day, 2-mg/day and 0-mg/day during weeks 1-3, respectively) with an opioid-abstinence incentive ($30 per consecutive opioid-negative urine specimen, obtained thrice weekly). Results Participants who reported less pre-study (past-month) heroin use and shorter lifetime duration of heroin use were more likely to submit an opioid-negative urine sample during initial outpatient BUP maintenance. Participants who reported more lifetime heroin-quit attempts and provided any opioid-free urine sample during initial outpatient maintenance sustained longer continuous opioid-abstinence during the BUP dose taper. Participants who reported >3 lifetime quit attempts abstained from opioid use nearly one week longer (14 vs. 8 days to opioid-lapse) and nearly half (46.7%) refrained from opioid use during dose taper. Conclusions Number of prior heroin quit attempts may predict BUP dose taper response and provide a metric for stratifying heroin-dependent individuals by relative risk for opioid lapse. This metric may inform personalized relapse prevention care and improve treatment outcomes. PMID:25479914

  18. Expanding substance use treatment options for HIV prevention with Buprenorphine-Naloxone: HIV Prevention Trials Network 058 (HPTN 058)

    PubMed Central

    Metzger, David S.; Donnell, Deborah; Celentano, David D.; Jackson, J. Brooks; Shao, Yiming; Aramrattana, Apinun; Wei, Liu; Fu, Liping; Ma, Jun; Lucas, Gregory M.; Chawarski, Marek; Ruan, Yuhua; Richardson, Paul; Shin, Katherine; Chen, Ray Y.; Sugarman, Jeremy; Dye, Bonnie J.; Rose, Scott M.; Beauchamp, Geetha; Burns, David N.

    2015-01-01

    Background Injection opioid use plays a significant role in the transmission of HIV infection in many communities and several regions of the world. Access to evidence-based treatments for opioid use disorders is extremely limited. Methods HPTN 058 was a randomized controlled trial designed to compare the impact of two medication assisted treatment (MAT) strategies on HIV incidence or death among opioid dependent people who inject drugs (PWID). HIV-negative opiate dependent PWID were recruited from four communities in Thailand and China with historically high prevalence of HIV among PWID. 1251 participants were randomly assigned to either; 1) a one year intervention consisting of two opportunities for a 15 day detoxification with buprenorphine/naloxone (BUP/NX) combined with up to 21 sessions of behavioral drug and risk counseling (Short Term Medication Assisted Treatment: ST-MAT) or, 2) thrice weekly dosing for 48 weeks with BUP/NX and up to 21 counseling sessions (Long Term Medication Assisted Treatment: LT-MAT) followed by dose tapering. All participants were followed for 52 weeks after treatment completion to assess durability of impact. Results While the study was stopped early due to lower than expected occurrence of the primary endpoints, sufficient data were available to assess the impact of the interventions on drug use and injection related risk behavior. At weeks 26, 22% of ST-MAT participants had negative urinalyses for opioids compared to 57% in the LT-MAT (p<0.001). Differences disappeared in the year following treatment: at week 78, 35% in ST-MAT and 32% in the LT-MAT had negative urinalyses. Injection related risk behaviors were significantly reduced in both groups following randomization. Conclusions Participants receiving BUP/NX three times weekly were more likely to reduce opioid injection while on active treatment. Both treatment strategies were considered safe and associated with reductions in injection related risk behavior. These data support

  19. Buprenorphine for office-based practice: consensus conference overview.

    PubMed

    Kosten, Thomas R; Fiellin, David A

    2004-01-01

    This overview of the March 2003 conference on the U.S. national buprenorphine implementation program is developed to inform the practitioner about the positive experience that has been accumulated worldwide on the use of buprenorphine for office-based practice. The first paper delineates the challenges for American psychiatry in moving buprenorphine forward into general practice. Most psychiatrists are unprepared to work with opiate-dependent patients or to use buprenorphine. The international successes with office-based buprenorphine from France and Australia are presented in the next papers, followed by presentations on several U.S. studies using buprenorphine in the community for detoxification and office-based maintenance. These experiences have thus far confirmed buprenorphine's utility and promise for opiate addiction treatment in the U.S. Finally, two national monitoring programs have been implemented to assess the public health impact of this new treatment opportunity. This opportunity has a three-year window, however, and a critical need will be to attract a sufficient number of physicians into prescribing buprenorphine/naloxone in order to allow our patients increased access to this treatment. PMID:15204671

  20. Buprenorphine in combination with naloxone at a ratio of 15:1 does not enhance antinociception from buprenorphine in healthy cats.

    PubMed

    Slingsby, L S; Murrell, J C; Taylor, P M

    2012-06-01

    Naloxone can enhance the antinociceptive/analgesic effects of buprenorphine in humans and rats. The antinociceptive effects of a patented 15:1 buprenorphine:naloxone combination was investigated in cats using a thermal and mechanical nociceptive model. Twelve cats received buprenorphine 10 μg/kg, naloxone 0.67 μg/kg or a buprenorphine-naloxone combination intramuscularly in a randomised cross over study. Using thermal and mechanical analgesiometry validated in the cat, pre-treatment baselines were measured. Following test drug administration, thresholds were studied for the next 24h. Naloxone did not enhance the thermal antinociceptive effect of buprenorphine. The results from this study are in agreement with previously published work showing that naloxone antagonises the effects of clinically analgesic doses of buprenorphine. Mechanical nociceptive thresholds were not affected by buprenorphine. PMID:22030474

  1. Buprenorphine in the workers' compensation setting.

    PubMed

    Colameco, Stephen; Pohl, Mel

    2014-01-01

    Buprenorphine is approved by the Food and Drug Administration for the treatment of chronic pain in low-dose transdermal patch formulations and for the treatment of addiction in high-dose sublingual tablets and films. Clinicians often prescribe these high-dose preparations "off label" for pain management. In the workers' compensation setting, it is particularly important to consider factors such as a) if the injured person has, and is being treated for co-occurring addiction as well as pain; b) if alternative therapies, including opioid withdrawal, were considered prior to initiating buprenorphine treatment; and c) the anticipated duration of treatment. This article reviews buprenorphine's approved indications, formulations, pharmacology, clinical efficacy, and special considerations in the workers' compensation setting. PMID:25162607

  2. Abuse Potential of Intranasal Buprenorphine versus Buprenorphine/Naloxone in Buprenorphine-Maintained Heroin Users

    PubMed Central

    Jones, Jermaine D.; Sullivan, Maria A.; Vosburg, Suzanne K.; Manubay, Jeanne M.; Mogali, Shanthi; Metz, Verena; Comer, Sandra D.

    2014-01-01

    In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital for 8–9 weeks and were maintained on each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16 mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo, heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone typically produced increases in positive subjective effects and the 8 mg dose was self-administered above the level of placebo. The addition of naloxone dose-dependently reduced positive subjective effects and increased aversive effects. No buprenorphine/naloxone combination dose was self-administered significantly more than placebo. These data suggest that within a buprenorphine-dependent population, intranasal buprenorphine/naloxone has reduced abuse potential in comparison to buprenorphine alone. These data strongly argue in favor of buprenorphine/naloxone rather than buprenorphine alone as the more reasonable option for managing the risk of buprenorphine misuse. PMID:25060839

  3. Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-maintained heroin users.

    PubMed

    Jones, Jermaine D; Sullivan, Maria A; Vosburg, Suzanne K; Manubay, Jeanne M; Mogali, Shanthi; Metz, Verena; Comer, Sandra D

    2015-07-01

    In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16 mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo, heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone typically produced increases in positive subjective effects and the 8 mg dose was self-administered above the level of placebo. The addition of naloxone dose dependently reduced positive subjective effects and increased aversive effects. No buprenorphine/naloxone combination dose was self-administered significantly more than placebo. These data suggest that within a buprenorphine-dependent population, intranasal buprenorphine/naloxone has reduced abuse potential in comparison to buprenorphine alone. These data strongly argue in favor of buprenorphine/naloxone rather than buprenorphine alone as the more reasonable option for managing the risk of buprenorphine misuse. PMID:25060839

  4. Cost Analysis of Clinic and Office-based Treatment of Opioid Dependence: Results with Methadone and Buprenorphine in Clinically Stable Patients

    PubMed Central

    Jones, Emlyn S.; Moore, Brent A.; Sindelar, Jody L.; O’Connor, Patrick G.; Schottenfeld, Richard S.; Fiellin, David A.

    2009-01-01

    The cost of providing and receiving treatment for opioid dependence can determine its adoption. To compare the cost of clinic-based methadone (MC, n=23), office-based methadone (MO, n=21), and office-based buprenorphine (BO, n=34) we performed an analysis of treatment and patient costs over 6 months of maintenance in patients who had previously been stabilized for at least one year. We performed statistical comparisons using ANOVA and chi-square tests and performed a sensitivity analysis varying cost estimates and intensity of clinical contact. The cost of providing one month of treatment per patient was $147 (MC), $220 (MO) and $336 (BO) (p<0.001). Mean monthly medication cost was $93 (MC), $86 (MO) and $257 (BO) (p<0.001). The cost to patients was $92 (MC), $63 (MO) and $38 (BO) (p=0.102). Sensitivity analyses, varying cost estimates and clinical contact, result in total monthly costs of $117 to $183 (MC), $149 to $279 (MO), $292 to $499(BO). Monthly patient costs were $84 to $133 (MC), $55 to $105 (MO) and $34 to $65 (BO). We conclude that providing clinic-based methadone is least expensive. The price of buprenorphine accounts for a major portion of the difference in costs. For patients, office-based treatment may be less expensive. PMID:18804923

  5. Patient Perspectives on Choosing Buprenorphine over Methadone in an Urban Equal Access System

    PubMed Central

    Gryczynski, Jan; Jaffe, Jerome H.; Schwartz, Robert P.; Dušek, Kristi A.; Gugsa, Nishan; Monroe, Cristin L.; O'Grady, Kevin E.; Olsen, Yngvild K.; Mitchell, Shannon Gwin

    2014-01-01

    Background Recent policy initiatives in Baltimore City, MD significantly reduced access disparities between methadone and buprenorphine in the publicly-funded treatment sector. Objectives This study examines reasons for choosing buprenorphine over methadone among patients with access to both medications. Methods This study was embedded within a larger clinical trial conducted at two outpatient substance abuse treatment programs offering buprenorphine. Qualitative and quantitative data on treatment choice were collected for new patients starting buprenorphine treatment (n=80). The sample consisted of predominantly urban African American (94%) heroin users who had prior experience with non-prescribed street buprenorphine (85%) and opioid agonist treatment (68%). Qualitative data were transcribed and coded for themes, while quantitative data were analyzed using descriptive and bivariate statistics. Results Participants typically conveyed their choice of buprenorphine treatment as a decision against methadone. Buprenorphine was perceived as a helpful medication while methadone was perceived as a harmful narcotic with multiple unwanted physical effects. Positive experiences with non-prescribed “street buprenorphine” were a central factor in participants’ decisions to seek buprenorphine treatment. Conclusions Differences in service structure between methadone and buprenorphine did not strongly influence treatment-seeking decisions in this sample. Personal experiences with medications and the street narrative surrounding them play an important role in treatment selection decisions. Scientific Significance This study characterizes important decision factors that underlie patients’ selection of buprenorphine over methadone treatment. PMID:23617873

  6. Buprenorphine Buccal (chronic pain)

    MedlinePlus

    ... is taken as needed. Buprenorphine (Belbuca) in a class of medications called opiate partial agonists. It works ... an irregular heartbeat that may cause loss of consciousness or sudden death); if you have low levels ...

  7. Preliminary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral fluid and sweat during treatment of opioid-dependent pregnant women

    PubMed Central

    Concheiro, Marta; Jones, Hendreé E.; Johnson, Rolley E.; Choo, Robin; Huestis, Marilyn A.

    2011-01-01

    Background Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc) and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high dose (14–20 mg) BUP sublingual tablet administration in three opioid-dependent pregnant women. Methods Oral fluid and sweat specimens were collected in addition to plasma specimens for 24 h during gestation weeks 28 or 29 and 34, and 2 months after delivery. Tmax was not affected by pregnancy; however, BUP and NBUP Cmax and AUC0–24h tended to be lower during pregnancy compared to postpartum levels. Results Statistically significant but weak positive correlations were found for BUP plasma and OF concentrations, and BUP/NBUP ratios in plasma and OF. Conclusion Statistically significant negative correlations were observed for times of specimen collection and BUP and NBUP OF/plasma ratios. BUP-Gluc and NBUP-Gluc were detected in only 5% of OF specimens. In sweat, BUP and NBUP were detected in only 4 of 25 (12 or 24 h) specimens in low concentrations (<2.4 ng/patch). These preliminary data describe BUP and metabolite pharmacokinetics in pregnant women and suggest that, like methadone, upward dose adjustments may be needed with advancing gestation. PMID:21860340

  8. Buprenorphine may not be as safe as you think: a pediatric fatality from unintentional exposure.

    PubMed

    Kim, Hong K; Smiddy, Monica; Hoffman, Robert S; Nelson, Lewis S

    2012-12-01

    Buprenorphine is a partial μ-opioid receptor agonist that is approved for the treatment of opioid dependency. It is generally believed to be safer than methadone because of its ceiling effect on respiratory depression. As more adults in US households use buprenorphine, an increasing number of children are being exposed. We report a fatal exposure to buprenorphine in a small child that occurred after ingestion of a caretaker's buprenorphine/naloxone. Postmortem toxicology analysis showed free serum concentrations of 52 ng/mL and 39 ng/mL for buprenorphine and norbuprenorphine, respectively. No other drugs were detected. Autopsy did not find signs of injury or trauma. The theoretical safety provided by the ceiling effect in respiratory depression from buprenorphine may not apply to children, and buprenorphine may cause dose-dependent respiratory depression. PMID:23129079

  9. Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users.

    PubMed

    Alho, Hannu; Sinclair, David; Vuori, Erkki; Holopainen, Antti

    2007-04-17

    Buprenorphine (Subutex) is widely abused in Finland. A combination of buprenorphine plus naloxone (Suboxone) has been available since late 2004, permitting a comparison of the abuse of the two products among untreated intravenous (IV) users. A survey was distributed to attendees at a Helsinki needle exchange program over 2-weeks in April, 2005, At least 30% were returned anonymously. Survey variables included: years of prior IV opioid abuse, years of buprenorphine abuse, frequency, dosage, route of administration and reasons for use, concomitant IV abuse of other substances and amount paid on the street for both buprenorphine and buprenorphine+naloxone. Buprenorphine was the most frequently used IV drug for 73% of the respondents. More than 75% said they used IV buprenorphine to self-treat addiction or withdrawal. Most (68%) had tried the buprenorphine+naloxone combination IV, but 80% said they had a "bad" experience. Its street price was less than half that of buprenorphine alone. The buprenorphine+naloxone combination appears to be a feasible tool, along with easier access to addiction treatment, for decreasing IV abuse of buprenorphine. PMID:17055191

  10. Evaluation of the Tolerability of Switching Patients on Chronic Full μ-Opioid Agonist Therapy to Buccal Buprenorphine

    PubMed Central

    Gruener, Daniel; Kirby, Todd; Xiang, Qinfang; Tzanis, Evan; Finn, Andrew

    2016-01-01

    Objective Assess whether patients with chronic pain receiving 80 to 220 mg oral morphine sulfate equivalent of a full μ-opioid agonist could be transitioned to buccal buprenorphine at approximately 50% of their full dose without inducing opioid withdrawal or sacrificing analgesic efficacy. Methods. A randomized, double-blind, double-dummy, active-controlled, two-period crossover study in adult patients receiving around-the-clock full opioid agonist therapy and confirmed to be opioid dependent by naloxone challenge. Study doses were substituted at the time of the regular dose schedule for each patient. The primary endpoint was the proportion of patients with a maximum Clinical Opiate Withdrawal Scale score ≥ 13 (moderate withdrawal) or use of rescue medication. Results. 35 subjects on ≥ 80 mg morphine sulfate equivalent per day were evaluable for opioid withdrawal. One patient during buccal buprenorphine treatment and two during 50% full μ-opioid agonist treatment experienced opioid withdrawal of at least moderate intensity. The mean maximum Clinical Opiate Withdrawal Scale scores were similar, and numerically lower on buccal buprenorphine. There were no significant differences in pain ratings between treatments. The most frequent adverse events with buccal buprenorphine were headache (19%), vomiting (13%), nausea, diarrhea, and drug withdrawal syndrome (each 9%), and with full μ-opioid agonist were headache (16%), drug withdrawal syndrome (13%), and nausea (6%). Conclusions. Chronic pain patients treated with around-the-clock full μ-opioid agonist therapy can be switched to buccal buprenorphine (a partial μ-opioid agonist) at approximately 50% of the full μ-opioid agonist dose without an increased risk of opioid withdrawal or loss of pain control. PMID:26917621

  11. Buprenorphine/naloxone inhibition of remifentanil procedural sedation.

    PubMed

    Gilmore, Thomas; Saccheti, Al; Cortese, Teena

    2012-10-01

    Opioid analgesics are the mainstay of treatment of moderate and severe pain. Remifentanil is an ultrashort acting opioid analgesic used in emergency department (ED)procedural sedation, whereas buprenorphine/naloxone (Suboxone) is an opioid agonist-antagonist combination used in the treatment of addiction-prone individuals. We report here a case of buprenorphine/naloxone inhibition of remifentanil analgesia in a patient undergoing ED procedural sedation. PMID:22030204

  12. Opioid-induced constipation: rationale for the role of norbuprenorphine in buprenorphine-treated individuals.

    PubMed

    Webster, Lynn R; Camilleri, Michael; Finn, Andrew

    2016-01-01

    Buprenorphine and buprenorphine-naloxone fixed combinations are effective for managing patients with opioid dependence, but constipation is one of the most common side effects. Evidence indicates that the rate of constipation is lower when patients are switched from sublingual buprenorphine-naloxone tablets or films to a bilayered bioerodible mucoadhesive buccal film formulation, and while the bilayered buccal film promotes unidirectional drug flow across the buccal mucosa, the mechanism for the reduced constipation is unclear. Pharmacokinetic simulations indicate that chronic dosing of sublingually administered buprenorphine may expose patients to higher concentrations of norbuprenorphine than buprenorphine, while chronic dosing of the buccal formulation results in higher buprenorphine concentrations than norbuprenorphine. Because norbuprenorphine is a potent full agonist at mu-opioid receptors, the differences in norbuprenorphine exposure may explain the observed differences in treatment-emergent constipation between the sublingual formulation and the buccal film formulation of buprenorphine-naloxone. To facilitate the understanding and management of opioid-dependent patients at risk of developing opioid-induced constipation, the clinical profiles of these formulations of buprenorphine and buprenorphine-naloxone are summarized, and the incidence of treatment-emergent constipation in clinical trials is reviewed. These data are used to propose a potential role for exposure to norbuprenorphine, an active metabolite of buprenorphine, in the pathophysiology of opioid-induced constipation. PMID:27366109

  13. Current knowledge of buprenorphine and its unique pharmacological profile.

    PubMed

    Pergolizzi, Joseph; Aloisi, Anna Maria; Dahan, Albert; Filitz, Joerg; Langford, Richard; Likar, Rudolf; Mercadante, Sebastiano; Morlion, Bart; Raffa, Robert B; Sabatowski, Rainer; Sacerdote, Paola; Torres, Luis M; Weinbroum, Avi A

    2010-01-01

    Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other μ-opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full μ-opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain. PMID:20492579

  14. Rewarding or aversive effects of buprenorphine/naloxone combination (Suboxone) depend on conditioning trial duration.

    PubMed

    Canestrelli, Corinne; Marie, Nicolas; Noble, Florence

    2014-09-01

    Buprenorphine is used as a sublingual medication in the treatment of opioid dependence. However, its misuse by i.v. injection may limit its acceptability and dissemination. A buprenorphine/naloxone (ratio 4:1) combination has been developed to reduce diversion and abuse. So far, the relevance of this combination has not been investigated in the animal models traditionally used to study the reinforcing effects of drugs of abuse. The aim of this study was to compare the rewarding effects, assessed by conditioned place preference (CPP), of buprenorphine and buprenorphine/naloxone combination following i.v. administration in mice. Animals were treated with different doses of buprenorphine or buprenorphine/naloxone combination (ratio 4:1), and CPP conditioning trial duration was 5 or 30 min. At the longest trial duration, a bell-shaped dose-response curve was obtained with buprenorphine, which was shifted significantly to the right with naloxone combination. At the shortest trial duration, an aversive effect was observed with the buprenorphine/naloxone combination in animals, involving opioid receptor-like 1 (ORL1). These findings may explain the discrepancies reported in the literature as some authors have shown a reduced buprenorphine/naloxone misuse compared to buprenorphine in opioid abusers, while others have not. PMID:24606726

  15. Buprenorphine Prescribing: To Expand or Not to Expand.

    PubMed

    Li, Xiaofan; Shorter, Daryl; Kosten, Thomas R

    2016-05-01

    As a result of the prescription opioid epidemic in the United States, there has been an increasing need for effective treatment interventions, both pharmacological and nonpharmacological. Buprenorphine has emerged as a critical component of the treatment of opioid use disorder, yet its adoption has not been without some concerns. This article first reviews the pharmacology, clinical use, and US legislative action related to buprenorphine, followed by a discussion of the misuse and diversion of buprenorphine in the United States as well as internationally. We then explore the impact of buprenorphine abuse as well as discussing strategies for its reduction, including changes in policy, prescription and pharmacy monitoring, and continuing medical education for guiding and improving clinical practice. PMID:27123798

  16. Buprenorphine Maintenance Therapy in Opioid-Addicted Health Care Professionals Returning to Clinical Practice: A Hidden Controversy

    PubMed Central

    Hamza, Heather; Bryson, Ethan O.

    2012-01-01

    It remains controversial whether it is safe for recovering health care professionals to return to clinical practice after treatment for drug addiction. One specific component of reentry that remains particularly contentious is the use of pharmacotherapeutics, specifically buprenorphine, as opioid substitution therapy for health care professionals who wish to return to clinical work. Because health care professionals are typically engaged in safety-sensitive work with considerable consequences when errors occur, abstinence-based recovery should be recommended until studies demonstrate that it is safe to allow this population to practice while undergoing opioid substitution therapy. PMID:22386182

  17. PREVALENCE AND CORRELATES OF STREET-OBTAINED BUPRENORPHINE USE AMONG CURRENT AND FORMER INJECTORS IN BALTIMORE, MARYLAND

    PubMed Central

    Genberg, Becky L.; Gillespie, Mirinda; Schuster, Charles R.; Johanson, Chris-Ellyn; Astemborski, Jacquie; Kirk, Gregory D.; Vlahov, David; Mehta, Shruti H.

    2013-01-01

    Objectives There are few systematic assessments of street-obtained buprenorphine use from community-based samples in the United States. The objective of this study was to characterize the prevalence, correlates, and reasons for street-obtained buprenorphine use among current and former injection drug users (IDUs) in Baltimore, Maryland. Methods In 2008, participants of the ALIVE (AIDS Linked to the IntraVenous Experience) study, a community-based cohort of IDUs, were administered a survey on buprenorphine. Street-obtained buprenorphine represented self-reported use of buprenorphine obtained from the street or a friend in the prior three months. Results 602 respondents were predominantly male (65%), African-American (91%), and 30% were HIV-positive. Overall, nine percent reported recent street-obtained buprenorphine use, and only 2% reported using to get high. Among active opiate users, 23% reported recent use of street-obtained buprenorphine. Use of buprenorphine prescribed by a physician, injection and non-injection drug use, use of street-obtained methadone and prescription opiates, homelessness, and opioid withdrawal symptoms were positively associated, while methadone treatment, health insurance, outpatient care, and HIV-infection were negatively associated with recent street-obtained buprenorphine use in univariate analysis. After adjustment, active injection and heroin use were positively associated with street-obtained buprenorphine use. Ninety-one percent reported using street-obtained buprenorphine to manage withdrawal symptoms. Conclusions While 9% reported recent street-obtained buprenorphine use, only a small minority reported using buprenorphine to get high, with the majority reporting use to manage withdrawal symptoms. There is limited evidence of diversion of buprenorphine in this sample and efforts to expand buprenorphine treatment should continue with further monitoring. PMID:24018232

  18. Population Pharmacokinetic Modeling After Repeated Administrations of RBP-6000, a New, Subcutaneously Injectable, Long-Acting, Sustained-Release Formulation of Buprenorphine, for the Treatment of Opioid Use Disorder.

    PubMed

    Laffont, Celine M; Gomeni, Roberto; Heidbreder, Christian; Jones, J P; Nasser, Azmi F

    2016-07-01

    RBP-6000 is a novel sustained-release formulation of buprenorphine for the treatment of opioid use disorder, which has been designed for once-monthly (28 days) subcutaneous (SC) injections. A population pharmacokinetic (PK) model was developed to describe the time course of buprenorphine plasma concentrations after repeated SC injections of RBP-6000 at 50 mg, 100 mg, 200 mg, or 300 mg in treatment-seeking opioid-dependent subjects previously on sublingual buprenorphine (Subutex(®) ) treatment. The μ-opioid receptor occupancy was predicted using a previously developed PK/PD Emax model. The results of the population PK analysis jointly with the predicted level of μ-opioid receptor occupancy provided quantitative criteria for clinical dose selection for RBP-6000: the dose of 300 mg every 28 days seems appropriate for immediately achieving an effective exposure after the first SC injection and to maintain effective levels of exposure during chronic treatment. Furthermore, simulations conducted to evaluate the potential impact of a holiday in drug intake indicated that in the unexpected event of a 2-week holiday, levels of μ-opioid receptor occupancy remained consistently above 70% with no significant loss of drug efficacy. This analysis indicated that RBP-6000 has the potential for becoming an effective treatment for opioid-dependent subjects by addressing compliance issues associated with the current once-a-day treatments. PMID:26479717

  19. Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS.

    PubMed

    Marin, Stephanie J; McMillin, Gwendolyn A

    2016-01-01

    Buprenorphine (Suboxone, Zubsolv, Buprenex, Butrans, etc.) is an opioid drug that has been used to treat opioid dependence on an outpatient basis, and is also prescribed for managing moderate to severe pain. Pregnant women may be prescribed buprenorphine as part of a treatment plan for opioid addiction. This chapter quantitates buprenorphine and norbuprenorphine in meconium by liquid chromatography tandem mass spectrometry (LC-MS/MS). PMID:26660174

  20. A review of the studies using buprenorphine in cats.

    PubMed

    Steagall, P V M; Monteiro-Steagall, B P; Taylor, P M

    2014-01-01

    Pain management is a crucial component of feline medicine and surgery. This review critically evaluates studies using buprenorphine in cats and highlights the clinical application of the opioid in this species. The pharmacokinetic-pharmacodynamic (PK-PD) modeling of IV buprenorphine has been best described by a combined effect compartmental/receptor association-dissociation model with negative hysteresis. Therefore, plasma concentrations of the drug are not correlated with analgesia, and clinicians should not expect to observe pain relief immediately after drug administration. In addition, a ceiling effect has not been demonstrated after administration of clinical doses of buprenorphine in cats; dosages of up to 0.04 mg/kg have been reported. The route of administration influences the onset, duration, and magnitude of antinociception and analgesia when using this drug in cats. At clinical dosages, the SC route of administration does not appear to provide adequate antinociception and analgesia whereas the buccal route has produced inconsistent results. Intravenous or IM administration at a dosage of 0.02-0.04 mg/kg is the preferred for treatment of pain in the acute setting. A literature search found 14 clinical trials evaluating buprenorphine sedation, analgesia, or both in cats. There were 22 original research studies reporting the antinociceptive effects of buprenorphine by means of thermal threshold, mechanical threshold, or both, minimal alveolar concentration, or PK-PD. Individual variability in response to buprenorphine administration has been reported, indicating that buprenorphine may not provide sufficient analgesia in some cats. Pain assessment is important when evaluating the efficacy of buprenorphine and determining whether additional analgesic treatment is needed. PMID:24655078

  1. Pregabalin Abuse amongst Opioid Substitution Treatment Patients.

    PubMed

    McNamara, S; Stokes, S; Kilduff, R; Shine, A

    2015-01-01

    Pregabalin (Lyrica®) is used in treating epilepsy, nerve pain and anxiety. Pregabalin was initially thought to have a low misuse potential however there are emerging reports of Pregabalin being abused. A study was commenced at the National Drug Treatment Centre's (NDTC) Drug Analysis Laboratory to determine the level of usage of Pregabalin within the addiction services population in Ireland. A total of 498 urine samples representing samples from 440 individual opioid substitution patients, initially screened by immunoassay for drugs of abuse, were subjected to further analysis for Pregabalin by Liquid Chromatography/Mass Spectrometry (LC/MS). Of 440 patients tested, 39 tested positive for Pregabalin (9.2%). Only 10 patients from this group were prescribed this drug to our knowledge thus giving an estimated rate of misuse of 7.0%. Other drugs detected in the Pregabalin positive patients were Opiates (31.8%), Cocaine (11.4%), Benzodiazepines (79.5%) and Cannabis (77.8%). Our study confirms that Pregabalin abuse is taking place amongst the addiction services population. We believe that misuse of this prescription drug is a serious emerging issue which should be monitored carefully. PMID:26817289

  2. Effect of telaprevir on the pharmacokinetics of buprenorphine in volunteers on stable buprenorphine/naloxone maintenance therapy.

    PubMed

    Luo, Xia; Trevejo, Jose; van Heeswijk, Rolf P G; Smith, Frances; Garg, Varun

    2012-07-01

    This was an open-label, single-sequence trial in hepatitis C virus-negative volunteers on stable, individualized, buprenorphine maintenance therapy. Telaprevir at 750 mg every 8 h was coadministered with buprenorphine/naloxone (4:1 ratio as sublingual tablets) for 7 days with food. Pharmacokinetic profiles of buprenorphine, norbuprenorphine, and naloxone were measured over the 24-hour dosing interval on day -1 (buprenorphine/naloxone alone, reference) and day 7 of telaprevir coadministration (test). Geometric least-squares mean ratios and associated 90% confidence intervals of treatment ratios (test/reference) were calculated using log-transformed pharmacokinetic parameters. Opioid withdrawal symptoms were evaluated throughout the study (via questionnaires and pupillometry). Pharmacokinetic data were available for 14 and 13 volunteers on day -1 and day 7, respectively. The area under the concentration-time curve (AUC) for buprenorphine was unchanged and the maximum concentration of drug in serum (C(max)) for buprenorphine, C(max) and AUC for norbuprenorphine, and C(max) naxolone were modestly decreased during coadministration with telaprevir. Geometric least-squares mean ratios (90% confidence intervals) for buprenorphine were 0.80 (0.69, 0.93) for the C(max) and 0.96 (0.84, 1.10) for the AUC from 0 to 24 h (AUC(0-24)); for norbuprenorphine, values were 0.85 (0.66, 1.09) for C(max) and 0.91 (0.71, 1.16) for AUC(0-24); for naloxone, the C(max) was 0.84 (0.62, 1.13). Coadministration of telaprevir did not increase withdrawal symptom frequency, and there were no serious adverse events reported during or after completion of telaprevir coadministration. Results suggest dose adjustment may not be necessary when telaprevir and buprenorphine/naloxone are coadministered. PMID:22564847

  3. Effect of Telaprevir on the Pharmacokinetics of Buprenorphine in Volunteers on Stable Buprenorphine/Naloxone Maintenance Therapy

    PubMed Central

    Luo, Xia; Trevejo, Jose; van Heeswijk, Rolf P. G.; Smith, Frances

    2012-01-01

    This was an open-label, single-sequence trial in hepatitis C virus-negative volunteers on stable, individualized, buprenorphine maintenance therapy. Telaprevir at 750 mg every 8 h was coadministered with buprenorphine/naloxone (4:1 ratio as sublingual tablets) for 7 days with food. Pharmacokinetic profiles of buprenorphine, norbuprenorphine, and naloxone were measured over the 24-hour dosing interval on day −1 (buprenorphine/naloxone alone, reference) and day 7 of telaprevir coadministration (test). Geometric least-squares mean ratios and associated 90% confidence intervals of treatment ratios (test/reference) were calculated using log-transformed pharmacokinetic parameters. Opioid withdrawal symptoms were evaluated throughout the study (via questionnaires and pupillometry). Pharmacokinetic data were available for 14 and 13 volunteers on day −1 and day 7, respectively. The area under the concentration-time curve (AUC) for buprenorphine was unchanged and the maximum concentration of drug in serum (Cmax) for buprenorphine, Cmax and AUC for norbuprenorphine, and Cmax naxolone were modestly decreased during coadministration with telaprevir. Geometric least-squares mean ratios (90% confidence intervals) for buprenorphine were 0.80 (0.69, 0.93) for the Cmax and 0.96 (0.84, 1.10) for the AUC from 0 to 24 h (AUC0–24); for norbuprenorphine, values were 0.85 (0.66, 1.09) for Cmax and 0.91 (0.71, 1.16) for AUC0–24; for naloxone, the Cmax was 0.84 (0.62, 1.13). Coadministration of telaprevir did not increase withdrawal symptom frequency, and there were no serious adverse events reported during or after completion of telaprevir coadministration. Results suggest dose adjustment may not be necessary when telaprevir and buprenorphine/naloxone are coadministered. PMID:22564847

  4. From research to the real world: buprenorphine in the decade of the Clinical Trials Network.

    PubMed

    Ling, Walter; Jacobs, Petra; Hillhouse, Maureen; Hasson, Albert; Thomas, Christie; Freese, Thomas; Sparenborg, Steven; McCarty, Dennis; Weiss, Roger; Saxon, Andrew; Cohen, Allan; Straus, Michele; Brigham, Gregory; Liu, David; McLaughlin, Paul; Tai, Betty

    2010-06-01

    The National Institute on Drug Abuse (NIDA) established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to bring researchers and treatment providers together to develop a clinically relevant research agenda. Initial CTN efforts addressed the use of buprenorphine, a mu-opioid partial agonist, as treatment for opioid dependence. Strong evidence of buprenorphine's therapeutic efficacy was demonstrated in clinical trials involving several thousand opioid-dependent participants, and in 2002, the Food and Drug Administration approved buprenorphine for the treatment of opioid dependence. With the advent of a sublingual tablet containing both buprenorphine and naloxone to mitigate abuse and diversion (Suboxone), buprenorphine appeared poised to be the first-line treatment for opioid addiction. Notwithstanding its many attributes, certain implementation barriers remained to be addressed in CTN studies, and these efforts have brought a body of knowledge on buprenorphine to frontline clinicians. The purpose of this article is to review CTN-based buprenorphine research and related efforts to overcome challenges to the implementation of buprenorphine therapy in mainstream practice. Furthermore, this article explores current issues and future challenges that may require additional CTN efforts. PMID:20307796

  5. Methadone and buprenorphine-naloxone are effective in reducing illicit buprenorphine and other opioid use, and reducing HIV risk behavior – Outcomes of a Randomized Trial

    PubMed Central

    Otiashvili, David; Piralishvili, Gvantsa; Sikharulidze, Zura; Kamkamidze, George; Poole, Sabrina; Woody, George E.

    2013-01-01

    Aims Determine the extent to which buprenorphine injectors continue treatment with buprenorphine-naloxone or methadone, and the impact of these treatments on substance use and HIV risk in the Republic of Georgia. Methods Randomized controlled 12-week trial of daily-observed methadone or buprenorphine-naloxone followed by a dose taper, referral to ongoing treatment, and follow-up at week 20 at the Uranti Clinic in Tbilisi, Republic of Georgia. Eighty consenting treatment-seeking individuals (40/group) aged 25 and above who met ICD-10 criteria for opioid dependence with physiologic features and reported injecting buprenorphine 10 or more times in the past 30 days. Opioid use according to urine tests and self-reports, treatment retention, and HIV risk behavior as determined by the Risk Assessment Battery. Results Mean age of participants was 33.7 (SD5.7), 4 were female, mean history of opioid injection use was 5.8 years (SD4.6), none were HIV+ at intake or at the 12-week assessment and 73.4% were HCV+. Sixty-eight participants (85%) completed the 12-week medication phase (33 from methadone and 35 from buprenorphine/naloxone group); 37 (46%) were in treatment at the 20-week follow-up (21 from methadone and 16 from the buprenorphine/naloxone group). In both study arms, treatment resulted in a marked reduction in unprescribed buprenorphine, other opioid use, and HIV injecting risk behavior with no clinically significant differences between the two treatment arms. Conclusions Daily observed methadone or buprenorphine-naloxone are effective treatments for non-medical buprenorphine and other opioid use in the Republic of Georgia and likely to be useful for preventing HIV infection. PMID:23916321

  6. HIV Treatment Outcomes Among HIV-Infected, Opioid-Dependent Patients Receiving Buprenorphine/Naloxone Treatment within HIV Clinical Care Settings: Results From a Multisite Study

    PubMed Central

    Altice, Frederick L.; Bruce, R. Douglas; Lucas, Gregory M.; Lum, Paula J.; Korthuis, P. Todd; Flanigan, Timothy P.; Cunningham, Chinazo O.; Sullivan, Lynn E.; Vergara-Rodriguez, Pamela; Fiellin, David A.; Cajina, Adan; Botsko, Michael; Nandi, Vijay; Gourevitch, Marc N.; Finkelstein, Ruth

    2012-01-01

    Background Having opioid dependence and HIV infection are associated with poor HIV-related treatment outcomes. Methods HIV-infected, opioid-dependent subjects (N = 295) recruited from 10 clinical sites initiated buprenorphine/naloxone (BUP/NX) and were assessed at baseline and quarterly for 12 months. Primary outcomes included receiving antiretroviral therapy (ART), HIV-1 RNA suppression, and mean changes in CD4 lymphocyte count. Analyses were stratified for the 119 subjects not on ART at baseline. Generalized estimating equations were deployed to examine time-dependent correlates for each outcome. Results At baseline, subjects on ART (N = 176) were more likely than those not on ART (N = 119) to be older, heterosexual, have lower alcohol addiction severity scores, and lower HIV-1 RNA levels; they were less likely to be homeless and report sexual risk behaviors. Subjects initiating BUP/NX (N = 295) were significantly more likely to initiate or remain on ART and improve CD4 counts over time compared with baseline; however, these improvements were not significantly improved by longer retention on BUP/NX. Retention on BUP/NX for three or more quarters was, however, significantly associated with increased likelihood of initiating ART (β = 1.34 [1.18, 1.53]) and achieve viral suppression (β = 1.25 [1.10, 1.42]) for the 64 of 119 (54%) subjects not on ART at baseline compared with the 55 subjects not retained on BUP/NX. In longitudinal analyses, being on ART was positively associated with increasing time of observation from baseline and higher mental health quality of life scores (β = 1.25 [1.06, 1.46]) and negatively associated with being homo- or bisexual (β = 0.55 [0.35, 0.97]), homeless (β = 0.58 [0.34, 0.98]), and increasing levels of alcohol addiction severity (β = 0.17 [0.03, 0.88]). The strongest correlate of achieving viral suppression was being on ART (β = 10.27 [5.79, 18.23]). Female gender (β = 1.91 [1.07, 3.41]), Hispanic ethnicity (β = 2.82 [1.44, 5

  7. The New Kid on the Block--Incorporating Buprenorphine into a Medical Toxicology Practice.

    PubMed

    Wiegand, Timothy J

    2016-03-01

    Buprenorphine represents a safe and effective therapy for treating opioid dependence, alleviating craving and withdrawal symptoms in opioid-dependent patients. Buprenorphine has a "blocking" effect against the action of other opioids at the mu-receptor, preventing not only opioid-induced euphoria, but CNS and respiratory depressant effects as well. Buprenorphine was approved for the treatment of opioid dependence in 2002 after the passage of Drug Abuse Treatment Act 2000 (DATA 2000) which allowed clinicians to treat opioid-dependent patients with specifically named opioid agonist therapies in an office setting. Buprenorphine programs reduce the prevalence of HIV and hepatitis C and reduce criminal behaviors associated with illicit drug use. Patients stabilized on buprenorphine have increased employment, enhanced engagement with social services, and better overall health and well-being. PMID:26574020

  8. New developments in the management of opioid dependence: focus on sublingual buprenorphine-naloxone.

    PubMed

    Soyka, Michael

    2015-01-01

    Opioid maintenance therapy is a well-established first-line treatment approach in opioid dependence. Buprenorphine, a partial opioid agonist, has been found by numerous studies to be an effective and safe medication in the treatment of opioid dependence. At present, buprenorphine is available as a monodrug or in a fixed 4:1 ratio combination with naloxone. A diminished risk of diversion and abuse for the buprenorphine-naloxone combination is likely but not firmly established. Conventional formulations are given sublingually to avoid the hepatic first-pass effect. A novel film tablet is available only in the US and Australia. Other novel, sustained-release formulations (implant, depot) are currently being developed and tested. Recent studies, including a Cochrane meta-analysis, suggest that the retention with buprenorphine is lower than for methadone, but that buprenorphine may be associated with less drug use. Higher doses of buprenorphine are associated with better retention rates. Buprenorphine has a ceiling effect at the opioid receptor with regard to respiratory depression, and may cause fewer fatal intoxications than methadone. Possible antidepressant effects of buprenorphine and its use in comorbid psychiatric patients has not been studied in much detail. Clinical implications are discussed. PMID:25610012

  9. Buprenorphine Maintenance for Opioid Dependence in Public Sector Healthcare: Benefits and Barriers

    PubMed Central

    Duncan, Laura G.; Mendoza, Sonia; Hansen, Helena

    2015-01-01

    Background Since its U.S. FDA approval in 2002, buprenorphine has been available for maintenance treatment of opiate dependence in primary care physicians’ offices. Though buprenorphine was intended to facilitate access to treatment, disparities in utilization have emerged; while buprenorphine treatment is widely used in private care setting, public healthcare integration of buprenorphine lags behind. Results Through a review of the literature, we found that U.S. disparities are partly due to a shortage of certified prescribers, concern of patient diversion, as well as economic and institutional barriers. Disparity of buprenorphine treatment dissemination is concerning since buprenorphine treatment has specific characteristics that are especially suited for low-income patient population in public sector healthcare such as flexible dosing schedules, ease of concurrently treating co-morbidities such as HIV and hepatitis C, positive patient attitudes towards treatment, and the potential of reducing addiction treatment stigma. Conclusion As the gap between buprenorphine treatment in public sector settings and private sector settings persists in the U.S., current research suggests ways to facilitate its dissemination. PMID:27088135

  10. A meta-analysis of efficacy and tolerability of buprenorphine for the relief of cancer pain.

    PubMed

    Naing, Cho; Yeoh, Peng Nam; Aung, Kyan

    2014-01-01

    This study aimed to synthesize available evidence on the analgesic efficacy of buprenorphine in treating cancer pain and related adverse effects. We searched electronic databases for randomized controlled trials, assessing the efficacy of buprenorphine, regardless of delivery system. The primary endpoints were patient-reported 'pain intensity' and 'pain relief'. Statistical heterogeneity among included studies was assessed with the I (2) test. The summary relative risk (RR) and 95% CI were derived, if two or more studies reported the similar outcome. Sixteen RCTs (n = 1329) with buprenorphine were included: 8 transdermal (TD), 5 sublingual (SL), 2 intramuscular injection (IM) and 1 subcutaneous infusion (SC) studies; with both SL and IM routes being assessed in one study. Only a few studies reported the same outcome in a similar way, creating difficulty for pooling of the outcome data. Many studies had a high risk of bias. In 2 studies (n = 241), the 'global impression change' was significantly different between TD buprenorphine and the combined placebo and morphine (RR 1.35, 95% CI 1.14-1.59; I (2): 42%); the 'number-needed-to-treat' (NNT) was 4.9 (95% CI: 3.1-10.9). In 2 studies (n = 331), 'requirement for rescue SL buprenorphine' was comparable between TD buprenorphine and placebo (RR 1.25, 95% CI 0.71-2.18; I (2) : 40%). In 2 studies (n = 141), 'incidence of nausea' was less in TD buprenorphine (RR: 0.38, 95% CI: 0.2-0.71, I (2): 0%, NNT: 9.3, 5.6-28.5). Due to the small number of participants in a small number of studies, the results of the present review provide insufficient evidence to position adequately the use of buprenorphine in treatment of cancer pain. Large multicenter RCTs that compare TD buprenorphine with standard analgesic treatment is needed to position TD buprenorphine in the therapeutic armamentarium of cancer pain treatment. PMID:24600544

  11. Buprenorphine Reduces Alcohol Drinking Through Activation of the Nociceptin/Orphanin FQ-NOP Receptor System

    PubMed Central

    Ciccocioppo, Roberto; Economidou, Daina; Rimondini, Roberto; Sommer, Wolfgang; Massi, Maurizio; Heilig, Markus

    2011-01-01

    Background Activation of the NOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats. Here we evaluated whether buprenorphine, a partial agonist at μ-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors. Methods Marchigian Sardinian alcohol preferring rats trained to drink 10% alcohol 2 hours/day were injected with buprenorphine (.03, .3, 3.0, or 6.0 mg/kg intraperitoneally [IP]) 90 min before access to ethanol. Results Similar to prototypical μ-agonists, the two lowest doses of buprenorphine significantly increased ethanol consumption (p < .01); in contrast, the two highest doses reduced it (p < .05). Pretreatment with naltrexone (.25 mg/kg IP) prevented the increase of ethanol intake induced by .03 mg/kg of buprenorphine (p < .001) but did not affect the inhibition of ethanol drinking induced by 3.0 mg/kg of buprenorphine. Conversely, pretreatment with the selective NOP receptor antagonist UFP-101 (10.0 or 20.0 μg/rat) abolished the suppression of ethanol drinking by 3.0 mg/kg of buprenorphine. Conclusions Buprenorphine has dualistic effects on ethanol drinking; low doses increase alcohol intake via stimulation of classic opioid receptors, whereas higher doses reduce it via activation of NOP receptors. We suggest that NOP agonistic properties of buprenorphine might be useful in the treatment of alcoholism. PMID:16533497

  12. The Implementation of Buprenorphine/Naloxone in College Health Practice

    ERIC Educational Resources Information Center

    DeMaria, Peter A., Jr.; Patkar, Ashwin A.

    2008-01-01

    Opiate abuse and dependence have become important concerns for college healthcare providers. The passage of the Drug Addiction Treatment Act of 2000 and the approval of the combination buprenorphine/naloxone for office-based treatment of opiate dependence have increased the options available for college students and their healthcare providers. The…

  13. Comparison of two formulations of buprenorphine in cats administered by the oral transmucosal route.

    PubMed

    Bortolami, Elisa; Slingsby, Louisa; Love, Emma J

    2012-08-01

    This randomised, blinded, cross-over study investigated the ease of oral transmucosal administration of two formulations of buprenorphine using glucose as a control in 12 cats. The cats received three treatments: buprenorphine multi-dose, buprenorphine and the equivalent volume of glucose 5%. Ease of treatment administration, observation of swallowing, changes in pupil size, sedation, salivation, vomiting, behaviour and food intake were assessed. The data were analysed using MLwiN and multi-level modelling. Ease of administration of buprenorphine multi-dose was statistically different from glucose (P <0.001), and the administration of all treatments became easier over the study periods. Swallowing was not statistically different between groups (P >0.05). Mydriasis was evident after the administration of both formulations of buprenorphine. Sedation, salivation, vomiting, behavioural changes or in-appetence were not observed after any treatment. Cats tolerated oral transmucosal administration of glucose better than buprenorphine multi-dose, while buprenorphine administration was tolerated as well as glucose. PMID:22403414

  14. Buprenorphine Sublingual and Buccal (opioid dependence)

    MedlinePlus

    ... slurred speech unusual bleeding or bruising lack of energy pain in the upper right part of the stomach yellowing of the skin or eyes dark-colored urine light-colored stools Buprenorphine or buprenorphine ...

  15. A combination of buprenorphine and naltrexone blocks compulsive cocaine intake in rodents without producing dependence.

    PubMed

    Wee, Sunmee; Vendruscolo, Leandro F; Misra, Kaushik K; Schlosburg, Joel E; Koob, George F

    2012-08-01

    Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non-opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent μ opioid antagonist with weaker δ and κ antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence. The effects of buprenorphine and various doses of naltrexone on cocaine self-administration were assessed in rats that self-administered cocaine under conditions of either short access (noncompulsive cocaine seeking) or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly decreased cocaine self-administration. Although this buprenorphine-alone effect was blocked in a dose-dependent manner by naltrexone in both the short-access and the extended-access groups, the combination of the lowest dose of naltrexone with buprenorphine blocked cocaine self-administration in the extended-access group but not in the short-access group. Rats given this low dose of naltrexone with buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in rats treated with buprenorphine alone, and naltrexone at this dose did not block κ agonist-induced analgesia. The results suggest that the combination of buprenorphine and naltrexone at an appropriate dosage decreases compulsive cocaine self-administration with minimal liability to produce opioid dependence and may be useful as a treatment for cocaine addiction. PMID:22875830

  16. A novel approach in the detoxification of intravenous buprenorphine dependence

    PubMed Central

    Sarkar, Sukanto; Subramaniam, Eswaran; Konthoujam, Janet

    2016-01-01

    Background: Opioid dependence remains a significant problem in India, and of late intravenous (IV) buprenorphine use has increased in India, especially in combination with antihistamines and benzodiazepines. Its usage has many serious consequences in the form of needle-transmitted hepatitis and HIV, which is showing an increasing trend. Buprenorphine is a partial agonist at μ-opioid receptors. In tablet form (and rarely as IV), it is widely used in the treatment of opioid detoxification. We assessed the safety and efficacy of transdermal patch of buprenorphine with week long duration of action in the treatment of detoxification of IV buprenorphine dependence in view of its many advantages. Materials and Methods: Six consecutive patients with International Classification of Diseases diagnosis of Opioid Dependence Syndrome (IV buprenorphine) were given a buprenorphine patch for treatment of withdrawal symptoms after receiving consent. Severity of opioid dependence was assessed by using Severity of Opioid Dependence Questionnaire on the day of presentation. Subjective and objective rating for opioid withdrawal was done by subjective opiate withdrawal scale (SOWS) and objective opiate withdrawal scale (OOWS) prepatch and postpatch 3rd and 7th day. Buprenorphine side effect checklist was applied on a daily basis. Results: The patients had a mean age of 30 years, of whom 83.3% are males. All were educated and 50% were currently employed. All of them had additional comorbid substance use as well as a comorbid psychiatric diagnosis. Each of them received a patch of varying dosage. The patch dose used initially was based on clinical considerations alone and was fairly adequate in controlling acute withdrawal symptoms. There is a significant improvement in SOWS and OOWS while comparing the baseline (prepatch) with 3rd and 7th day (postpatch) (P ≤ 0.05). None of the patients reported any side effect with the patch. Conclusion: This study shows that transdermal

  17. Colocating buprenorphine with methadone maintenance and outpatient chemical dependency services.

    PubMed

    Whitley, Susan D; Kunins, Hillary V; Arnsten, Julia H; Gourevitch, Marc N

    2007-07-01

    Buprenorphine may be used to treat opioid dependence in office-based settings, but treatment models are needed to ensure access to psychosocial services needed by many patients. We describe a novel buprenorphine treatment program colocated with methadone maintenance and outpatient chemical dependency services. We conducted a retrospective chart review of the first 40 consecutive patients initiating buprenorphine treatment in this program to determine characteristics associated with treatment retention. Exclusion criteria were current alcohol or benzodiazepine dependence. Secondary drug users and patients who were psychiatrically or medically ill were included. At 6 months, 60% (n = 24) were retained, 13% (n = 5) tested positive for opiates, and 25% (n = 10) tested positive for secondary substances. Patients who were older (odds ratio [OR] per year of age = 1.1, confidence interval [CI] = 1.0-1.2) and those who were employed (OR = 9.8, CI = 1.8-53.1) were more likely to remain in treatment, but other variables were not associated with retention. Our experience demonstrates that buprenorphine can be successfully integrated into outpatient substance abuse treatment. PMID:17588493

  18. Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?

    PubMed

    Blum, Kenneth; Chen, Thomas J H; Bailey, John; Bowirrat, Abdalla; Femino, John; Chen, Amanda L C; Simpatico, Thomas; Morse, Siobhan; Giordano, John; Damle, Uma; Kerner, Mallory; Braverman, Eric R; Fornari, Frank; Downs, B William; Rector, Cynthia; Barh, Debmayla; Oscar-Berman, Marlene

    2011-12-01

    Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence, the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research, the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate that buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that, to date, this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target

  19. Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?

    PubMed Central

    Blum, Kenneth; Chen, Thomas JH; Bailey, John; Bowirrat, Abdulla; Femino, John; Chen, Amanda LC; Simpatico, Thomas; Morse, Siobhan; Giordano, John; Damle, Uma; Kerner, Mallory; Braverman, Eric R.; Fornari, Frank; Downs, B.William; Rector, Cynthia; Barh, Debmayla; Oscar-Berman, Marlene

    2013-01-01

    Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that to date this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target the

  20. Opioid-induced constipation: rationale for the role of norbuprenorphine in buprenorphine-treated individuals

    PubMed Central

    Webster, Lynn R; Camilleri, Michael; Finn, Andrew

    2016-01-01

    Buprenorphine and buprenorphine–naloxone fixed combinations are effective for managing patients with opioid dependence, but constipation is one of the most common side effects. Evidence indicates that the rate of constipation is lower when patients are switched from sublingual buprenorphine–naloxone tablets or films to a bilayered bioerodible mucoadhesive buccal film formulation, and while the bilayered buccal film promotes unidirectional drug flow across the buccal mucosa, the mechanism for the reduced constipation is unclear. Pharmacokinetic simulations indicate that chronic dosing of sublingually administered buprenorphine may expose patients to higher concentrations of norbuprenorphine than buprenorphine, while chronic dosing of the buccal formulation results in higher buprenorphine concentrations than norbuprenorphine. Because norbuprenorphine is a potent full agonist at mu-opioid receptors, the differences in norbuprenorphine exposure may explain the observed differences in treatment-emergent constipation between the sublingual formulation and the buccal film formulation of buprenorphine–naloxone. To facilitate the understanding and management of opioid-dependent patients at risk of developing opioid-induced constipation, the clinical profiles of these formulations of buprenorphine and buprenorphine-naloxone are summarized, and the incidence of treatment-emergent constipation in clinical trials is reviewed. These data are used to propose a potential role for exposure to norbuprenorphine, an active metabolite of buprenorphine, in the pathophysiology of opioid-induced constipation. PMID:27366109

  1. Using buprenorphine for outpatient opioid detoxification.

    PubMed

    Manlandro, James J

    2007-09-01

    The Drug Addiction Treatment Act of 2000 (DATA 2000) was established to create a new paradigm for medication-assisted treatment of persons with opiate addiction in the United States. Before enactment of DATA 2000, the use of opioid medications to treat patients with opioid addiction was permissible only in federally approved treatment programs, ie, "methadone clinics." The only medications permitted were Schedule II drugs (eg, methadone hydrochloride and l-alpha-acetylmethadol [LAAM]), which could only be dispensed, not prescribed. Under provisions of DATA 2000, qualified physicians in a medical office and other appropriate settings outside the opioid treatment program system may prescribe and/or dispense Schedule III, IV, and V opioid medications for treating persons with opioid addiction if such medications have been specifically approved by the US Food and Drug Administration for that indication. Opioid addiction treatment programs were commonly known as methadone clinics. Such programs now may also dispense buprenorphine hydrochloride and the buprenorphine hydrochloride-naloxone combination. PMID:17908825

  2. Opioid Abstinence Reinforcement Delays Heroin Lapse during Buprenorphine Dose Tapering

    ERIC Educational Resources Information Center

    Greenwald, Mark K.

    2008-01-01

    A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n = 12) received $4.00 for completing…

  3. Five Year Experience with Collaborative Care of Opioid Addicted Patients using Buprenorphine in Primary Care

    PubMed Central

    Alford, Daniel P.; LaBelle, Colleen T.; Kretsch, Natalie; Bergeron, Alexis; Winter, Michael; Botticelli, Michael; Samet, Jeffrey H.

    2010-01-01

    Background Opioid addiction is a chronic disease treatable in primary care settings with buprenorphine, but this treatment remains underutilized. We describe a collaborative care model for managing opioid addiction with buprenorphine. Methods This is a cohort study of patients treated for opioid addiction utilizing collaborative care between nurse care managers and generalist physicians in an urban academic primary care practice over 5 years. We examine patient characteristics, 12-month treatment success (i.e., retention or taper after 6 months), and predictors of successful outcomes. Results From 2003 to 2008, 408 patients with opioid addiction were treated with buprenorphine. Twenty-six patients were excluded from analysis as they left treatment due to preexisting legal or medical conditions or a need for transfer to another buprenorphine program. At 12 months 51% of patients (196/382) underwent successful treatment. Of patients remaining in treatment at 3-, 6-, 9- and 12 months, 93% were no longer using illicit opioids or cocaine based on urine drug tests. On admission, patients who were older, employed, and used illicit buprenorphine had significantly higher odds of treatment success; those of African American or Hispanic race had significantly lower odds of treatment success. These outcomes were achieved with a model that facilitated physician involvement. Conclusions Collaborative care with nurse care managers in an urban primary care practice is an alternative and successful method of service delivery for the majority of patients with opioid addiction while effectively utilizing the time of physicians prescribing buprenorphine. PMID:21403039

  4. Thienorphine is a potent long-acting partial opioid agonist: a comparative study with buprenorphine.

    PubMed

    Yu, Gang; Yue, Yong-Juan; Cui, Meng-Xun; Gong, Ze-Hui

    2006-07-01

    A strategy in the development of new treatment for opioid addiction is to find partial opioid agonists with properties of long duration of action and high oral bioavailability. In a search for such compounds, thienorphine, a novel analog of buprenorphine, was synthesized. Here, we reported that, like buprenorphine, thienorphine bound potently and nonselectively to mu-, delta-, and kappa-opioid receptors stably expressed in CHO (Chinese hamster ovary) cells and behaved as a partial agonist at mu-opioid receptor. However, some differences were observed between the pharmacological profiles of thienorphine and buprenorphine. In vitro, thienorphine was more potent than buprenorphine in inhibiting [3H]diprenorphine and stimulating guanosine 5'-O-(3-[35S]thio)triphosphate binding to rat mu-opioid receptor stably expressed in CHO cells. In vivo, thienorphine exhibited a less potent but more efficacious antinociceptive effect with an ED50 value of 0.25 mg/kg s.c. and more potent antimorphine effect with an ED50 value of 0.64 mg/kg intragastric, compared with buprenorphine. Additionally, the bioavailability of thienorphine was greatly higher than that of buprenorphine after oral administration. Moreover, compared with buprenorphine, thienorphine showed a similar long-lasting antinociceptive effect but a much longer antagonism of morphine-induced lethality (more than 15 days). These results indicate that thienorphine is a potent, long-acting partial opioid agonist with high oral bioavailability and may have possible application in treating addiction. PMID:16569757

  5. Buprenorphine prescribing practices and exposures reported to a poison center--Utah, 2002-2011.

    PubMed

    2012-12-14

    Buprenorphine is an effective medication for the treatment of opioid dependence. Its use has increased in the United States as a result of the Drug Addiction Treatment Act of 2000, which allowed physicians to prescribe certain medications as part of office-based treatment for opioid addiction. In France, widespread use of medication-assisted therapy, primarily buprenorphine treatment, was associated with an 80% decrease in overdose deaths from heroin or cocaine from 465 in 1996 to 89 in 2003. With the expanded use of buprenorphine, an increase in exposures among children and adults has been reported in the United States. These exposures (including unintentional and intentional, therapeutic and nontherapeutic) have resulted in adverse effects and, in a small number of cases, death. To assess statewide increases in buprenorphine use and the number of reported exposures, the Utah Department of Health analyzed data from the Utah Controlled Substance Database (CSD) and the Utah Poison Control Center (PCC). The results of that analysis indicated a statewide increase in the annual number of patients prescribed buprenorphine from 22 in 2002 to 9,793 in 2011, and a concurrent increase in the annual number of prescribers writing buprenorphine prescriptions from 16 to 1,088. Over the same period, the number of exposures to buprenorphine reported annually to the PCC increased from six to 81. However, comparison of the ratios of buprenorphine exposures to patients and prescribers in 2002 with data for 2011 indicated substantial decreases from 6/22 for patients and 6/16 for prescribers in 2002 to 81/9,793 for patients and 81/1,088 for prescribers in 2011. Three of the total 462 buprenorphine exposures reported during 2002-2011 in Utah, in a teen and two adults, were associated with fatal outcomes. Increased buprenorphine prescribing in Utah during 2002-2011 likely represents expanded access to critically needed opioid addiction treatment; however, safeguards should be in place

  6. [Transdermal buprenorphine: a current overview of pharmacological and clinical data].

    PubMed

    Faymonville, M E; Libbrecht, D

    2008-11-01

    Our understanding of the pathophysiologic mechanisms of chronic pain progresses; the complexity of the problem justifies our need for new molecules and new ways of administration that will help to further optimise and better individualize our pharmacologic therapies. Whereas acute pain can be considered an alarm signal, chronic pain constitutes, per se, a syndrome that requires a meticulous selection of the analgesic drug(s). Since pain is permanent, the continuous administration of the analgesic is recommended rather than an on demand administration. Transdermic modes of administration are of value for the treatment of chronic pain because they allow a progressive delivery of the active compound together with the maintenance of stable plasma levels of the drug. Buprenorphine is a semi-synthetic opioid that is available in the sublingual, injectable, or transdermic forms. The matrix patch of buprenorphine represents a major asset for the treatment of chronic pain, whether it be cancerous in origin, or not. Its efficacy and safety have been clearly demonstrated in randomised double blind trials as well as in post-marketing surveillance observations. Buprenorphine, administered as a transdermal therapeutic system, induces a dose-related pain relief, whatever the nature of the pain and the age of the patient. Buprenorphine also exerts an analgesic action on neuropathic pain. It differs from other opioids by its affinity as a partial agonist on mu and kappa receptors, and as a complete agonist of ORL-1 receptors. Therefore, transdermal buprenorphine will be useful to all physicians having to control severe pain by powerful opioids. PMID:19112993

  7. Combined administration of buprenorphine and naltrexone produces antidepressant-like effects in mice.

    PubMed

    Almatroudi, Abdulrahman; Husbands, Stephen M; Bailey, Christopher P; Bailey, Sarah J

    2015-07-01

    Opiates have been used historically for the treatment of depression. Renewed interest in the use of opiates as antidepressants has focused on the development of kappa opioid receptor (κ-receptor) antagonists. Buprenorphine acts as a partial µ-opioid receptor agonist and a κ-receptor antagonist. By combining buprenorphine with the opioid antagonist naltrexone, the activation of µ-opioid receptors will be reduced and the κ-antagonist properties enhanced. We have established that a combination dose of buprenorphine (1 mg/kg) with naltrexone (1 mg/kg) functions as a short-acting κ-antagonist in the mouse tail withdrawal test. Furthermore, this dose combination is neither rewarding nor aversive in the conditioned place preference paradigm, and is without significant locomotor effects. We have shown for the first time that systemic co-administration of buprenorphine (1 mg/kg) with naltrexone (1 mg/kg) in CD-1 mice produced an antidepressant-like response in behaviours in both the forced swim test and novelty induced hypophagia task. Behaviours in the elevated plus maze and light dark box were not significantly altered by treatment with buprenorphine alone, or in combination with naltrexone. We propose that the combination of buprenorphine with naltrexone represents a novel, and potentially a readily translatable approach, to the treatment of depression. PMID:26045511

  8. An unusual case of death probably triggered by the association of buprenorphine at therapeutic dose with ethanol and benzodiazepines and with very low norbuprenorphine level.

    PubMed

    Bardy, Guillaume; Cathala, Philippe; Eiden, Céline; Baccino, Eric; Petit, Pierre; Mathieu, Olivier

    2015-01-01

    Buprenorphine is largely prescribed for maintenance treatment in opioid dependence due to its safety profile. Nevertheless, fatalities at therapeutic dose have been described when associated with other central nervous system depressants, such as ethanol or benzodiazepines. Here, we report a case of death due to association of buprenorphine at therapeutic dose with benzodiazepines and ethanol. Although toxicity has been often attributed to its metabolite norbuprenorphine rather than to buprenorphine itself, in our case, norbuprenorphine was not detected in urine and bile and only in traces in blood. Moreover, the presence in blood of free buprenorphine but not of glucuronide metabolites argues for an unusual early death, at the beginning of buprenorphine metabolism. We propose that in the context of prior toxic impregnation, buprenorphine directly (and not via its metabolite norbuprenorphine) acted as a triggering factor by blocking the ventilatory response, rapidly leading to fatal respiratory depression. PMID:25348172

  9. The history of the development of buprenorphine as an addiction therapeutic.

    PubMed

    Campbell, Nancy D; Lovell, Anne M

    2012-02-01

    This paper traces the early 21st century success of the agonist-antagonist buprenorphine and the combination drug buprenorphine with naloxone within the broader quest to develop addiction therapeutics that began in the 1920s as the search for a nonaddictive analgesic. Drawing on archival research, document analysis, and interviews with contemporary actors, this paper situates the social organization of laboratory-based and clinical research within the domestic and international confluence of several issues, including research ethics, drug regulation, public attitudes, tensions around definitions of drug addiction, and the evolving roles of the pharmaceutical industry. The fervor that drove the champions of buprenorphine must be understood in relation to (1) the material work of research and pharmaceutical manufacturing; (2) the symbolic role of buprenorphine as a solution to numerous problems with addiction treatment evident by the mid-1970s; the destigmatization and individualization of addicts as patients; and (3) the complex configurations of public and private partnerships. PMID:22256949

  10. Discontinuation of Buprenorphine Maintenance Therapy: Perspectives and Outcomes

    PubMed Central

    Bentzley, Brandon S.; Barth, Kelly S.; Back, Sudie E.; Book, Sarah W.

    2015-01-01

    Buprenorphine maintenance therapy (BMT) is increasingly the preferred opioid maintenance agent due to its reduced toxicity and availability in an office-based setting in the United States. Although BMT has been shown to be highly efficacious, it is often discontinued soon after initiation. No current systematic review has yet investigated providers’ or patients’ reasons for BMT discontinuation or the outcomes that follow. Hence, provider and patient perspectives associated with BMT discontinuation after a period of stable buprenorphine maintenance and the resultant outcomes were systematically reviewed with specific emphasis on pre-buprenorphine-taper parameters predictive of relapse following BMT discontinuation. Few identified studies address provider or patient perspectives associated with buprenorphine discontinuation. Within the studies reviewed providers with residency training in BMT were more likely to favor long term BMT instead of detoxification, and providers were likely to consider BMT discontinuation in the face of medication misuse. Patients often desired to remain on BMT because of fear of relapse to illicit opioid use if they were to discontinue BMT. The majority of patients who discontinued BMT did so involuntarily, often due to failure to follow strict program requirements, and 1 month following discontinuation, rates of relapse to illicit opioid use exceeded 50% in every study reviewed. Only lower buprenorphine maintenance dose, which may be a marker for attenuated addiction severity, predicted better outcomes across studies. Relaxed BMT program requirements and frequent counsel on the high probability of relapse if BMT is discontinued may improve retention in treatment and prevent the relapse to illicit opioid use that is likely to follow BMT discontinuation. PMID:25601365

  11. Buprenorphine alters ethanol self-administration in rats: dose-response and time-dependent effects.

    PubMed

    June, H L; Cason, C R; Chen, S H; Lewis, M J

    1998-11-01

    Buprenorphine is a partial opioid agonist derived from thebaine and has high affinity for mu and kappa opioid receptors. The present study investigated dose-response (0.03, 0.15, 0.3, 3 mg/kg) and time-dependent effects of buprenorphine (1.5 or 4 h post-treatment) on EtOH self-administration in outbred Sprague-Dawley rats. Freely feeding and drinking rats were trained to initiate EtOH self-administration for 1 h daily using the ascending concentration procedure, wherein they were provided with increasing concentrations of EtOH at 2, 5, 7, 9 and 11% (v/v), respectively. Water was concurrently available with each concentration. Animals were maintained on a given concentration of EtOH for 5 days. By day 21, animals began their stabilization on the 11% regimen and remained on this concentration throughout the remainder of the study. EtOH and water consumption were recorded daily at both 10- and 60-min intervals. At 1.5 h post-buprenorphine, all test doses greatly suppressed both EtOH and water intake at the 10-min interval. At the 60-min interval, all but the lowest dose (0.03 mg/kg) significantly suppressed EtOH intake, while only the highest dose (3 mg/kg) suppressed water intake. In contrast to the suppressant profile observed at 1.5 h post-buprenorphine, at 4 h post-buprenorphine the lower doses (0.03 and 0.15 mg/kg) significantly increased EtOH intake while the higher doses (0.3 and 3 mg/kg) continued to suppress intake. None of the doses of buprenorphine altered water intake 4 h post-buprenorphine. The results support previous research demonstrating the utility of low doses of buprenorphine in suppressing behavior rewarded by a non-opioid drug. PMID:9862399

  12. Buprenorphine detection in hair samples by immunometric screening test: preliminary experience.

    PubMed

    Svaizer, Fiorenza; Lotti, Andrea; Gottardi, Massimo; Miozzo, Maria Pia

    2010-03-20

    The recent introduction of buprenorphine use by the Drug Addiction Services has induced toxicology laboratories to develop new qualitative or semiquantitative screening assay for its determination in hair samples. The aim of this preliminary study was to verify the correlation between the buprenorphine intake and the immunometric screening test results (VMA-T Comedical and buprenorphine CEDIA/Thermo-Fisher/Microgenics reagents) and therefore their comparison with the liquid chromatography coupled with mass spectrometry (LC/MS) results. Hair samples were obtained from 32 subjects without buprenorphine-therapy reported and 17 in treatment. In glass test tube with hermetic cap were weighed 33 mg of 49 finely cut hair samples, washed with 1 mL of SLV-VMA-T washing solution, which is then completely sucked and eliminated. The samples were extracted with 400 microL of VMA-T reagent for an hour at 100 degrees C. The extracts were analysed by immunometric screening test on ILab 650 chemistry analyser, using buprenorphine CEDIA reagent assay. From the 32 non-takers of drug, 30 semiquantitative results were less than 10 pg/mg and 2 were over 10 pg/mg; from the 17 subjects with therapy, all were over 10 pg/mg (range 13-50 pg/mg); no samples were false-negative. Results suggest that exist a good relationship between the administration of buprenorphine and its concentration in hair, detectable through this method and reagents line. PMID:20080369

  13. Buprenorphine-naloxone therapy in pain management.

    PubMed

    Chen, Kelly Yan; Chen, Lucy; Mao, Jianren

    2014-05-01

    Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone; Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggest that bup/nal may provide pain relief in patients with chronic pain with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent patients with chronic pain may include reversal of opioid-induced hyperalgesia and improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management. PMID:24509068

  14. BUPRENORPHINE-NALXONE THERAPY IN PAIN MANAGEMENT

    PubMed Central

    Chen, Kelly Yan; Chen, Lucy; Mao, Jianren

    2014-01-01

    Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone®, Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggests that bup/nal may provide pain relief in chronic pain patients with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent chronic pain patients may include reversal of opioid-induced hyperalgesia as well as improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management. PMID:24509068

  15. Use and misuse of buprenorphine in the management of opioid addiction.

    PubMed

    Cicero, Theodore J; Surratt, Hilary L; Inciardi, James

    2007-01-01

    Buprenorphine was approved in late 2004 for the treatment of opioid abuse and dependence in specially trained and certified physicians' offices. At the time of the approval, there was a regulatory concern that given the anticipated wide exposure there would be unexpectedly high levels of abuse in the high-risk population for which it was intended. To assess its abuse potential, the authors recruited more than 1000 individuals seeking treatment for prescription opioid abuse from 100 stand-alone (i.e., self-pay or insurance) drug abuse treatment programs around the country to determine whether they misused buprenorphine in the past 30 days to get high. The results indicate that there was a time-related increase in the number of subjects who used buprenorphine to get high, reaching 30-35 percent of individuals completing a questionnaire in the second quarter of 2006. At this time, it was equivalent to the misuse of methadone, both of which, however, were considerably lower than hydrocodone and oxycodone. Thereafter, the number of individuals using buprenorphine to get high dropped in a near linear fashion to less than 20 percent of those completing a questionnaire in the second quarter of 2007, significantly lower than that for methadone, oxycodone, and hydrocodone. The most likely interpretation of these data is that the poly-substance-abusing population, for whom buprenorphine is intended, experimented with this medication for its mood-altering effects for a period of time, but presumably because of its lack of euphorogenic properties, its use has now dissipated. Additionally, support for this conclusion is the very rare endorsement of buprenorphine as a primary drug (<3 percent of the total sample). Thus, the results indicate that it is unlikely that buprenorphine abuse will ever reach the epidemic that was feared by some regulatory groups and that its use in opioid detoxification and maintenance should continue. PMID:18290581

  16. Abuse and diversion of buprenorphine sublingual tablets and film.

    PubMed

    Lavonas, Eric J; Severtson, S Geoffrey; Martinez, Erin M; Bucher-Bartelson, Becki; Le Lait, Marie-Claire; Green, Jody L; Murrelle, Lenn E; Cicero, Theodore J; Kurtz, Steven P; Rosenblum, Andrew; Surratt, Hilary L; Dart, Richard C

    2014-07-01

    Buprenorphine abuse is common worldwide. Rates of abuse and diversion of three sublingual buprenorphine formulations (single ingredient tablets; naloxone combination tablets and film) were compared. Data were obtained from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Poison Center, Drug Diversion, Opioid Treatment (OTP), Survey of Key Informants' Patients (SKIP), and College Survey Programs through December 2012. To control for drug availability, event ratios (rates) were calculated quarterly, based on the number of patients filling prescriptions for each formulation ("unique recipients of a dispensed drug," URDD) and averaged and compared using negative binomial regression. Abuse rates in the OTP, SKIP, and College Survey Programs were greatest for single ingredient tablets, and abuse rates in the Poison Center Program and illicit diversion rates were greatest for the combination tablets. Combination film rates were significantly less than rates for either tablet formulation in all programs. No geographic pattern could be discerned. PMID:24680219

  17. The Baltimore Buprenorphine Initiative: understanding the role of buprenorphine in addressing heroin addiction in an urban-based community.

    PubMed

    Murphy, Lyn Stankiewicz; Oros, Marla T; Dorsey, Susan G

    2014-01-01

    Adequate drug treatment for substance users continues to be a challenge for most U.S. cities. To address heroin addiction in Baltimore, the Baltimore Buprenorphine Initiative was implemented as a joint project to promote individualized, patient-centered buprenorphine therapy in conjunction with behavioral treatment to accelerate recovery from opioid addiction. The purpose of this analysis was to explore differences in recovery trajectories predicting length of stay and use this information to predict characteristics that influence an individual's ability to remain in the Baltimore Buprenorphine Initiative program. The sample consisted of 1,039 subjects enrolled in the program between January 2008 and June 2009. The regression modeling determined that age, income, employment, and higher level of treatment were significant predictors of length of stay in the recovery program. The findings of this study have practical implications for the design and implementation of heroin addiction programs. The research indicates that focusing on these specific predictive variables early in the program design phase could increase recovery success rates as measured by length of stay. PMID:24613946

  18. Low-dose naloxone provides an abuse-deterrent effect to buprenorphine

    PubMed Central

    Webster, Lynn R; Smith, Michael D; Unal, Cemal; Finn, Andrew

    2015-01-01

    In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine–naloxone (BN) sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. This was a randomized, double-blind, placebo-controlled, single-dose, four-period crossover study in opioid-dependent subjects with chronic pain receiving >100 mg oral morphine equivalents daily who experienced withdrawal following a naloxone challenge dose. The objective of the study was to determine if intravenous (IV) naloxone doses of 0.1 and 0.2 mg would produce a withdrawal response when coadministered with a 0.75 mg IV dose of buprenorphine. Fifteen subjects receiving 90–1,260 mg oral morphine equivalents per day enrolled and completed the study. Precipitated withdrawal occurred in 13% (2/15) of placebo-treated subjects and 47% (7/15) of buprenorphine-treated subjects. When combined with the 0.75 mg dose of buprenorphine, a 0.1 mg dose of naloxone increased the incidence of precipitated withdrawal to 60%, and a 0.2 mg dose of naloxone increased the incidence to 73%. By 15 minutes postdose, the mean change in Clinical Opioid Withdrawal Scale (COWS) score from predose was 3.0 for placebo, 6.9 for buprenorphine, 9.8 for BN 0.1 mg, and 12.4 for BN 0.2 mg. The mean COWS score with each active treatment was significantly greater than placebo (P<0.001), and the mean COWS score for each of the naloxone-containing treatments was significantly greater than for buprenorphine alone (P<0.001). Naloxone doses as low as 0.1 mg added an abuse-deterrent effect to a 0.75 mg IV dose of buprenorphine. PMID:26604818

  19. Induction of opioid-dependent individuals onto buprenorphine and buprenorphine/naloxone soluble-films.

    PubMed

    Strain, E C; Harrison, J A; Bigelow, G E

    2011-03-01

    A sublingual soluble-film formulation of buprenorphine/naloxone (B/N) has been approved by the US Food and Drug Administration for the treatment of opioid dependency. This preparation provides unit-dose, child-resistant packaging amenable to tracking and accountability, offers more rapid dissolution, and has a potentially preferred taste vs. tablets. This study compared the ability of buprenorphine (B) and B/N films to suppress spontaneous withdrawal in opioid-dependent volunteers. Participants were maintained on morphine and underwent challenge sessions to confirm sensitivity to naloxone-induced opioid withdrawal. Subjects were randomized to receive either B (16 mg, n = 18) or B/N (16/4 mg, n = 16) soluble films for 5 days. The primary outcome measure was the Clinical Opiate Withdrawal Scale (COWS) score. Thirty-four subjects completed induction onto soluble films. There was a significant decrease in COWS scores but no significant differences between the groups. The results support the use of B and B/N soluble films as safe and effective delivery methods for opioid induction. PMID:21270789

  20. Maternal buprenorphine dose, placenta buprenorphine, and metabolite concentrations and neonatal outcomes.

    PubMed

    Concheiro, Marta; Jones, Hendreé E; Johnson, Rolley E; Choo, Robin; Shakleya, Diaa M; Huestis, Marilyn A

    2010-04-01

    Buprenorphine is approved as pharmacotherapy for opioid dependence in nonpregnant patients in multiple countries and is currently under investigation for pregnant women in the United States and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in five term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships among maternal buprenorphine dose, placenta concentrations, and neonatal outcomes after controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (coefficient of variation less than 27.5%, four locations), except for buprenorphine in three placentas. In two of these, buprenorphine was not detected in some locations and in the third placenta was totally absent. Median (range) concentrations were 1.6 ng/g buprenorphine (not detected to 3.2), 14.9 ng/g norbuprenorphine (6.2-24.2), 3 ng/g buprenorphine-glucuronide (1.3-5.0), and 14.7 ng/g norbuprenorphine-glucuronide (11.4-25.8). Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations (15- to 70-fold) than in meconium. Statistically significant correlations were observed for mean maternal daily dose from enrollment to delivery and placenta buprenorphine-glucuronide concentration and for norbuprenorphine-glucuronide concentrations and time to neonatal abstinence syndrome onset and duration, for norbuprenorphine/norbuprenorphine-glucuronide ratio and maximum neonatal abstinence syndrome score, and newborn length. Analysis of buprenorphine and metabolites in this alternative matrix, an abundant waste product available at the time of delivery, may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women. PMID:20216119

  1. Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans

    PubMed Central

    Huestis, M.A.; Cone, E.J.; Pirnay, S.O.; Umbricht, A.; Preston, K.L.

    2013-01-01

    Background Prescribed sublingual (SL) buprenorphine is sometimes diverted for intravenous (IV) abuse, but no human pharmacokinetic data are available following high-dose IV buprenorphine. Methods Plasma was collected for 72 h after administration of placebo or 2, 4, 8, 12, or 16 mg IV buprenorphine in escalating order (single-blind, double-dummy) in 5 healthy male non-dependent opioid users. Buprenorphine and its primary active metabolite, norbuprenorphine, were quantified by liquid chromatography tandem mass spectrometry with limits of quantitation of 0.1 μg/L. Results Maximum buprenorphine concentrations (mean ± SE) were detected 10 min after 2, 4, 8, 12, 16 mg IV: 19.3±1.0, 44.5±4.8, 85.2±7.7, 124.6±16.6, and 137.7±18.8 μg/L, respectively. Maximum norbuprenorphine concentrations occurred 10–15 min (3.7±0.7 μg/L) after 16 mg IV administration. Conclusions Buprenorphine concentrations increased in a significantly linear dose-dependent manner up to 12 mg IV buprenorphine. Thus, previously demonstrated pharmacodynamic ceiling effects (over 2–16 mg) are not due to pharmacokinetic adaptations within this range, although they may play a role at doses higher than 12 mg. PMID:23246635

  2. Effect of buprenorphine on total intravenous anesthetic requirements during spine surgery.

    PubMed

    Khelemsky, Yury; Schauer, Jacob; Loo, Nathaniel

    2015-01-01

    Buprenorphine is a partial mu receptor agonist and kappa/delta antagonist commonly used for the treatment of opioid dependence or as an analgesic. It has a long plasma half-life and a high binding affinity for opioid receptors. This affinity is so high, that the effects are not easily antagonized by competitive antagonists, such as naloxone. The high affinity also prevents binding of other opioids, at commonly used clinical doses, to receptor sites - preventing their analgesic and likely minimum alveolar concentration (MAC) reducing benefits. This case report contrasts the anesthetic requirements of a patient undergoing emergency cervical spine surgery while taking buprenorphine with anesthetic requirements of the same patient undergoing a similar procedure after weaning of buprenorphine. Use of intraoperative neurophysiological monitoring prevented use of paralytics and inhalational anesthetics during both cases, therefore total intravenous anesthesia (TIVA) was maintained with propofol and remifentanil infusions. During the initial surgery, intraoperative patient movement could not be controlled with very high doses of propofol and remifentanil. The patient stopped moving in response to surgical stimulation only after the addition of a ketamine. Buprenorphine-naloxone was discontinued postoperatively. Five days later the patient underwent a similar cervical spine surgery. She had drastically reduced anesthetic requirements during this case, suggesting buprenorphine's profound effect on anesthetic dosing. This case report elegantly illustrates that discontinuation of buprenorphine is likely warranted for patients who present for major spine surgery, which necessitates the avoidance of volatile anesthetic and paralytic agents. The addition of ketamine may be necessary in patients maintained on buprenorphine in order to ensure a motionless surgical field. PMID:25794231

  3. A Double Blind, within Subject Comparison of Spontaneous Opioid Withdrawal from Buprenorphine versus Morphine

    PubMed Central

    Smith, Michael T.; Mintzer, Miriam Z.; Campbell, Claudia M.; Strain, Eric C.

    2014-01-01

    Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical μ-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P < 0.05) greater than those of buprenorphine withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0–100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation. PMID:24227768

  4. Management of opioid addiction with buprenorphine: French history and current management.

    PubMed

    Poloméni, Pierre; Schwan, Raymund

    2014-01-01

    The way in which opioid addiction is managed in France is unique, as it is based on the prescription of buprenorphine by general practitioners and is dispensed by retail pharmacies. This policy has had a direct, positive impact on the number of deaths caused by heroin overdose, which was reduced by four-fifths between 1994 and 2002. In addition, certain associated comorbidities, such as infection with the human immunodeficiency virus, have also been reduced; the incidence of acquired immune deficiency syndrome in intravenous drug users fell from 25% in the mid-1990s to 6% in 2010. Since the implementation of this French model of opioid management, major scientific progress has been made, leading to a better understanding of the pathophysiologic mechanisms of addiction and of the management modalities required for its treatment. However, despite notable advances in scientific knowledge and in the implementation of devices, opioid addiction remains a major public health care issue in France, with 275,000-360,000 "problem drug users" being reported in 2011. The situation is still particularly worrying due to psychoactive substance use and misuse of opioid substitution treatments. Since 2003, there has been a persistent increase in the number of deaths and comorbidities related to opioid addiction, principally hepatitis C virus infection, which affects up to 40% of intravenous drug users. In France, the direct involvement of general practitioners in the management of opioid addiction is indisputable. Nevertheless, management could be optimized through better understanding of the pathophysiologic mechanisms of the disease, better knowledge of the pharmacology of opioid substitution treatments, and clear definition of short-, medium- and long-term treatment objectives. Data related to the management of opioid addiction by general practitioners in France have been published in 2005. Since then, the context has changed, other drugs were launched on the market such as

  5. Neonatal outcomes following in utero exposure to buprenorphine/naloxone or methadone

    PubMed Central

    Gawronski, Kristen M; Prasad, Mona R; Backes, Carl R; Lehman, K Joy; Gardner, Debra K

    2014-01-01

    Objectives: To study neonatal outcomes following buprenorphine/naloxone and methadone exposure during pregnancy. Methods: This study is a retrospective review of clinical and demographic information of 58 infants whose mothers were treated with buprenorphine/naloxone and 92 infants whose mothers were treated with methadone for opioid dependence during pregnancy. Results: Gestational age, birth weight, prematurity, admission to neonatal intensive care unit, and length of stay were similar between both groups of infants. Neonatal abstinence syndrome occurred less frequently among infants of mothers treated with buprenorphine/naloxone than those treated with methadone (64% and 80%, respectively, p = 0.03). All infants with neonatal abstinence syndrome were treated postnatally with methadone. There was a trend toward shorter duration of treatment and lower cumulative dosages of methadone among the buprenorphine/naloxone–exposed infants. Conclusions: No apparent significant adverse neonatal outcomes were detected following treatment with either maintenance medication; however, further prospective research is necessary to examine the safety and efficacy of buprenorphine/naloxone in pregnancy and its effects on the neonate. PMID:26770721

  6. Drug use and opioid substitution treatment for prisoners.

    PubMed

    Stöver, Heino; Michels, Ingo Ilja

    2010-01-01

    Drug use is prevalent throughout prison populations, and, despite advances in drug treatment programmes for inmates, access to and the quality of these programmes remain substantially poorer than those available for non-incarcerated drug users. Because prisoners may be at greater risk for some of the harms associated with drug use, they deserve therapeutic modalities and attitudes that are at least equal to those available for drug users outside prison. This article discusses drug use by inmates and its associated harms. In addition, this article provides a survey of studies conducted in prisons of opioid substitution therapy (OST), a clinically effective and cost-effective drug treatment strategy. The findings from this overview indicate why treatment efforts for drug users in prison are often poorer than those available for drug users in the non-prison community and demonstrate how the implementation of OST programmes benefits not only prisoners but also prison staff and the community at large. Finally, the article outlines strategies that have been found effective for implementing OST in prisons and offers suggestions for applying these strategies more broadly. PMID:20642849

  7. The effect of an electronic medicine dispenser on diversion of buprenorphine-naloxone-experience from a medium-sized Finnish city.

    PubMed

    Uosukainen, Hanna; Pentikäinen, Hannu; Tacke, Ulrich

    2013-07-01

    Providing unobserved opioid substitution treatment (OST) safely is a major challenge. This study examined whether electronic medicine dispensers (EMDs) can reduce diversion of take-home buprenorphine-naloxone (BNX) in a medium-sized Finnish city. All BNX treated OST patients in Kuopio received their take-home BNX in EMDs for 4months. EMDs' effect on diversion was investigated using questionnaires completed by patients (n=37) and treatment staff (n=19), by survey at the local needle exchange service and by systematic review of drug screen data from the Kuopio University Hospital. The majority of patients (n=21, 68%) and treatment staff (n=11, 58%) preferred to use EMDs for the safe storage of tablets. Five patients (16%) declared that EMDs had prevented them from diverting BNX. However, EMDs had no detectable effect on the availability or origin of illegal BNX or on the hospital-treated buprenorphine-related health problems. EMDs may improve the safety of storage of take-home BNX, but their ability to prevent diversion needs further research. PMID:23433750

  8. Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy

    PubMed Central

    Greenwald, Mark K.; Comer, Sandra D.; Fiellin, David A.

    2014-01-01

    Background Sublingual formulations of buprenorphine (BUP) and BUP/naloxone have well-established pharmacokinetic and pharmacodynamic profiles, and are safe and effective for treating opioid use disorder. Since approvals of these formulations, their clinical use has increased. Yet, questions have arisen as to how BUP binding to mu-opioid receptors (μORs), the neurobiological target for this medication, relate to its clinical application. BUP produces dose- and time-related alterations of μOR availability but some clinicians express concern about whether doses higher than those needed to prevent opioid withdrawal symptoms are warranted, and policymakers consider limiting reimbursement for certain BUP dosing regimens. Methods We review scientific data concerning BUP-induced changes in μOR availability and their relationship to clinical efficacy. Results Withdrawal suppression appears to require ≤50% μOR availability, associated with BUP trough plasma concentrations ≥1 ng/mL; for most patients, this may require single daily BUP doses of 4-mg to defend against trough levels, or lower divided doses. Blockade of the reinforcing and subjective effects of typical doses of abused opioids require <20% μOR availability, associated with BUP trough plasma concentrations ≥3 ng/mL; for most individuals, this may require single daily BUP doses >16-mg, or lower divided doses. For individuals attempting to surmount this blockade with higher-than-usual doses of abused opioids, even larger BUP doses and <10% μOR availability would be required. Conclusion For these reasons, and given the complexities of studies on this issue and comorbid problems, we conclude that fixed, arbitrary limits on BUP doses in clinical care or limits on reimbursement for this care are unwarranted. PMID:25179217

  9. Respiratory rates and arterial blood-gas tensions in healthy rabbits given buprenorphine, butorphanol, midazolam, or their combinations.

    PubMed

    Schroeder, Carrie A; Smith, Lesley J

    2011-03-01

    The objective of this study was to evaluate the respiratory effects of buprenorphine, butorphanol, midazolam, and their combinations in healthy conscious rabbits. Six adult female New Zealand white rabbits were anesthetized briefly with isoflurane by mask to allow placement of a catheter into the central ear artery. After a 60-min recovery period, a baseline arterial sample was obtained. Animals then were injected intramuscularly with either 0.9% NaCl (1 mL), buprenorphine (0.03 mg/kg), butorphanol (0.3 mg/kg), midazolam (2 mg/kg), buprenorphine + midazolam (0.03 mg/kg, 2 mg/kg), or butorphanol + midazolam (0.3 mg/kg, 2 mg/kg). Arterial blood gases were evaluated at 30, 60, 90, 120, 180, 240, and 360 min after drug administration. All drug treatments caused significant decreases in respiratory rate, compared with saline. Buprenorphine and the combinations of midazolam-butorphanol and midazolam-buprenorphine resulted in statistically significant decreases in pO(2). No significant changes in pCO(2) pressure were recorded for any treatment. Increases in blood pH were associated with administration of butorphanol, midazolam, and the combinations of midazolam-butorphanol and midazolam-buprenorphine. In light of these results, buprenorphine and the combinations of midazolam-buprenorphine and midazolam-butorphanol result in statistically significant hypoxemia in rabbits that breathe room air. The degree of hypoxemia is of questionable clinical importance in these healthy subjects. Hypoxemia resulting from these drug combinations may be amplified in rabbits with underlying pulmonary or systemic disease. PMID:21439214

  10. Hepatotoxicity in a 52-week randomized trial of short-term versus long-term treatment with buprenorphine/naloxone in HIV-negative injection opioid users in China and Thailand*

    PubMed Central

    Lucas, Gregory M.; Young, Alicia; Donnell, Deborah; Richardson, Paul; Aramrattana, Apinun; Shao, Yiming; Ruan, Yuhua; Liu, Wei; Fu, Liping; Ma, Jun; Celentano, David D.; Metzger, David; Jackson, J. Brooks; Burns, David

    2014-01-01

    Background Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, as persons taking BUP/NX have multiple hepatic risk factors, comparative data are needed to quantify the risk of hepatoxicity with BUP/NX. Methods We compared rates of alanine aminotransferase (ALT) elevation ≥ grade 3 (ALT ≥ 5.1 times the upper limit of normal) and graded bilirubin elevations in HIV-negative opioid injectors randomized to long-term (52 weeks) or short-term (18 days) medication assisted treatment (LT-MAT and ST-MAT, respectively) with BUP/NX in a multisite trial conducted in China and Thailand. ALT and bilirubin were measured at baseline, 12, 26, 40 and 52 weeks, times temporally remote from BUP/NX exposure in the ST-MAT participants. Results Among1036 subjects with at least one laboratory follow-up measurement, 76 (7%) participants experienced ALT elevation ≥ grade 3. In an intent-to-treat analysis, the risk of ALT events was similar in participants randomized to LT-MAT compared with ST-MAT (adjusted hazard ratio 1.25, 95% confidence interval 0.79 to 1.98). This finding was supported by an as-treated analysis, in which actual exposure to BUP/NX was considered. Hepatitis C seroconversion during follow-up was strongly associated with ALT events. Bilirubin elevations ≥ grade 2 occurred in 2% of subjects, with no significant difference between arms. Conclusions Over 52-week follow-up, the risk of hepatotoxicity was similar in opioid injectors receiving brief and prolonged treatment with BUP/NX. These data suggest that most hepatotoxic events observed during treatment with BUP/NX are due to other factors. PMID:24999060

  11. Management of opioid-dependent patients: comparison of the cost associated with use of buprenorphine/naloxone or methadone, and their interactions with concomitant treatments for infectious or psychiatric comorbidities.

    PubMed

    Roncero, Carlos; Domínguez-Hernández, Raquel; Díaz, Tomás; Fernández, José Manuel; Forcada, Rafael; Martínez, José Manuel; Seijo, Pedro; Terán, Antonio; Oyagüez, Itziar

    2015-01-01

    The objective was to estimate the annual interaction management cost of agonist opioid treatment (AOT) for opioid-dependent (OD) patients with buprenorphine-naloxone (Suboxone®) (B/N) or methadone associated with concomitant treatments for infectious (HIV) or psychiatric comorbidities. A costs analysis model was developed to calculate the associated cost of AOT and interaction management. The AOT cost included pharmaceutical costs, drug preparation, distribution and dispensing, based on intake regimen (healthcare center or take-home) and type and frequency of dispensing (healthcare center or pharmacy), and medical visits. The cost of methadone also included single-dose bottles, monthly costs of custody at pharmacy, urine toxicology drug screenings and nursing visits. Potential interactions between AOT and concomitant treatments (antivirals, antibacterials/antifungals, antipsychotics, anxiolytics, antidepressant and anticonvulsants), were identified to determine the additional use of healthcare resources for each interaction management. The annual cost per patient of AOT was €1,525.97 for B/N and €1,467.29 for methadone. The average annual cost per patient of interaction management was €257.07 (infectious comorbidities), €114.03 (psychiatric comorbidities) and €185.55 (double comorbidity) with methadone and €7.90 with B/N in psychiatric comorbidities. Total annual costs of B/N were €1,525.97, €1,533.87 and €1,533.87 compared to €1,724.35, €1,581.32 and €1,652.84 for methadone per patient with infectious, psychiatric or double comorbidity respectively.Compared to methadone, the total cost per patient with OD was lower with B/N (€47.45-€198.38 per year). This is due to the differences in interaction management costs associated with the concomitant treatment of infectious and/or psychiatric comorbidities. PMID:26437312

  12. 40 CFR 148.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Dilution prohibited as a substitute for treatment. 148.3 Section 148.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) HAZARDOUS WASTE INJECTION RESTRICTIONS General § 148.3 Dilution prohibited as a substitute for treatment....

  13. Parenteral buprenorphine-naloxone abuse is a major cause of fatal buprenorphine-related poisoning.

    PubMed

    Häkkinen, Margareeta; Heikman, Pertti; Ojanperä, Ilkka

    2013-10-10

    Buprenorphine (BPN) medication for opioid maintenance treatment in Finland consists predominantly of buprenorphine-naloxone (BNX). Both BPN and BNX are associated with diversion, abuse and non-medically supervised use worldwide. Our purpose was to estimate the proportion of BNX to all BPN-related fatalities. The material consisted of 225 deceased drug abusers in Finland from January 2010 to June 2011 with a positive BPN and/or norbuprenorphine (NOR) and/or naloxone (NX) finding in urine. The data were divided into three groups based on the urine NX and BPN concentrations. The "Parenteral BNX" group (>100 μg/l NX) was presumed to consist of injecting or snorting BNX abusers and the "Parenteral BPN" group (>50 μg/l BPN, 0 μg/l NX) of injecting or snorting BPN abusers, while the "Other BNX or BPN" group (≤100 μg/l NX, or ≤50 μg/l BPN combined with 0 μg/l NX) was presumed to consist of mainly sublingual BNX or BPN users. In 12.4% of cases the NX urine concentration was higher than the threshold 100 μg/l. In fatal BPN poisonings, the proportion of parenteral BNX was 28.4%. In the "Parenteral BNX", "Parenteral BPN" and "Other BNX or BPN" groups, the proportion of fatal BPN poisonings was 67.9, 31.0 and 22.6%, respectively. BNX abuse can be fatal. Among the 225 BPN-related fatalities, parenteral abuse of BNX was shown to be common (12.4%) and BNX poisoning was the underlying cause of death in 8.4%. Parenteral BNX caused fatal BPN poisoning proportionally more often than parenteral BPN. PMID:24053859

  14. The reinforcing and subjective effects of intravenous and intranasal buprenorphine in heroin users.

    PubMed

    Jones, Jermaine D; Madera, Gabriela; Comer, Sandra D

    2014-07-01

    Abuse of buprenorphine (BUP) by the intravenous (IV) route has been documented in several studies, and reports of intranasal (IN) abuse are increasing. However, no studies have directly compared the effects of BUP when it is administered intranasally and intravenously. The present secondary analysis used data from two separate studies to compare the reinforcing and subjective effects of IV and IN buprenorphine. One study evaluated IV buprenorphine (N=13) and the other evaluated IN buprenorphine (N=12). Participants were maintained on 2 mg sublingual (SL) BUP and tested with each intranasal or intravenous buprenorphine test dose (0 mg, 2 mg, 4 mg, 8 mg, and 16 mg). During morning laboratory sessions, participants received money (US $20) and sample doses of IN or IV BUP, and then completed subjective effects questionnaires. Later that day, they completed a self-administration task to receive 10% portions of the drug and/or money they previously sampled. In general, positive subjective ratings for both IV and IN BUP were significantly greater than placebo, with IV BUP having a greater effect than IN BUP. All active BUP doses (IV and IN) maintained significantly higher progressive ratio breakpoint values than placebo, but breakpoint values for IV BUP were greater than for IN BUP. Buprenorphine is an effective maintenance treatment for opioid dependence, valued for its ability to reduce the positive subjective effects of other opioids. Nevertheless, the present data demonstrate that in participants maintained on a low dose of SL BUP, the medication itself has abuse liability when used intravenously or intranasally. PMID:24793093

  15. Neonatal Outcomes and their Relationship to Maternal Buprenorphine Dose during Pregnancy

    PubMed Central

    Jones, Hendrée E.; Dengler, Erin; Garrison, Anna; O'Grady, Kevin E.; Seashore, Carl; Horton, Evette; Andringa, Kim; Jansson, Lauren M.; Thorp, John

    2014-01-01

    Background Buprenorphine pharmacotherapy for opioid-dependent pregnant women is associated with maternal and neonatal outcomes superior to untreated opioid dependence. However, the literature is inconsistent regarding the possible existence of a dose-response relationship between maternal buprenorphine dose and neonatal clinical outcomes. Methods The present secondary analysis study (1) examined the relationship between maternal buprenorphine dose at delivery and neonatal abstinence syndrome (NAS) peak score, estimated gestational age at delivery, Apgar scores at 1 and 5 minutes, neonatal head circumference, length, and weight at birth, amount of morphine needed to treat NAS, duration of NAS treatment, and duration of neonatal hospital stay; and (2) compared neonates who required pharmacotherapy for NAS to neonates who did not require such pharmacotherapy on these same outcomes, in 58 opioid-dependent pregnant women receiving buprenorphine as participants in a randomized clinical trial. Results (1) Analyses failed to provide evidence of a relationship between maternal buprenorphine dose at delivery and any of the 10 outcomes (all p-values>.48); and (2) significant mean differences between the untreated (n=31) and treated (n=27) for NAS groups were found for duration of neonatal hospital stay and NAS peak score (both p-values<.001). Conclusions (1) Findings failed to support the existence of a dose-response relationship between maternal buprenorphine dose at delivery and any of 10 neonatal clinical outcomes, including NAS severity; and (2) that infants treated for NAS had a higher mean NAS peak score and, spent a longer time in the hospital than did the group not treated for NAS is unsurprising. PMID:24290979

  16. [Dependence on psychotropic drugs and substitution treatment: recent trends. The OPPIDUM study of the Centers for Evaluation and Information on Drug Dependence (CEIP), October 1997].

    PubMed

    Thirion, X; Micallef, J; Guet, F; Delarozière, J C; Arditti, J; Huntsman, A; Sanmarco, J L; Lagier, G

    1999-01-01

    The aim of this study was to identify the latest trends in psychotropic drug use and the effect of the increase of maintenance treatments for serious opioid addiction. The results are based on data from OPPIDUM, an annual survey primarily concerned with the consumption of licit and illicit drugs. The study involved 1066 drug addicts recruited during the month of October 1997 from 38 French health centres connected with the Centres for Evaluation and Information on Drug Addiction (CEIP). The most frequently reported drugs were benzodiazepines (n = 323), some of which, especially flunitrazepam (Rohypnol, n = 123), are extremely addictive. The data showed a slight decrease in heroin consumption as well as a marked increase in the use of maintenance treatments. The association between benzodiazepines and buprenorphine (Subutex) should consequently be studied, whether buprenorphine is being used illicitly or prescribed as a maintenance treatment. PMID:10394261

  17. A review of buprenorphine diversion and misuse: the current evidence base and experiences from around the world.

    PubMed

    Lofwall, Michelle R; Walsh, Sharon L

    2014-01-01

    Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy has rapidly expanded in the United States and abroad, and, with this increase in medication availability, there have been increasing concerns about its diversion, misuse, and related harms. This narrative review defines the behaviors of diversion and misuse, examines how the pharmacology of buprenorphine alone and in combination with naloxone influence its abuse liability, and describes the epidemiological data on buprenorphine diversion and intravenous misuse, risk factors for its intravenous misuse, and the unintended consequences of misuse and diversion. Physician practices to prevent, screen for, and therapeutically respond to these behaviors, which are a form of medication nonadherence, are discussed, and gaps in knowledge are identified. Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy experiences from other countries that have varied health care systems, public policies, and access to addiction treatment are shared to make clear that diversion and misuse occur across the world in various contexts, for many different reasons, and are not limited to buprenorphine. Comparisons are made with other opioids with known abuse liability and medications with no known abuse. The objective was to facilitate understanding of diversion and misuse so that all factors influencing their expression (patient and provider characteristics and public policy) can be appreciated within a framework that also recognizes the benefits of addiction treatment. With this comprehensive perspective, further careful work can help determine how to minimize these behaviors without eroding the current benefits realized through improved addiction treatment access and expansion. PMID:25221984

  18. Comparison of side effects between buprenorphine and meloxicam used postoperatively in Dutch belted rabbits (Oryctolagus cuniculus).

    PubMed

    Cooper, Coreen S; Metcalf-Pate, Kelly A; Barat, Christopher E; Cook, Judith A; Scorpio, Diana G

    2009-05-01

    One of the challenges facing veterinarians and investigators who use rabbits (Oryctolagus cuniculus) as a surgical model in biomedical research is choosing an appropriate and efficacious postoperative analgesic without systemic complications and side effects. The objective of this study was to evaluate the gastrointestinal side effects associated with the postoperative use of buprenorphine in Dutch Belted rabbits. We also evaluated the analgesic meloxicam as an alternative to opioid administration during the postoperative period. Rabbits were assigned to 1 of 3 treatment groups during the postoperative period after routine ovariohysterectomy: buprenorphine (n = 10), meloxicam (n = 10), and incisional infiltration with bupivicaine (no treatment control; n = 10). Feed intake, fecal production, weight loss, urine output, and other physiologic parameters were monitored and behavior and pain assessments were performed for 7 d after surgery and compared with baseline values collected before surgery. All rabbits showed decreased pellet consumption, fecal production, and weight on day 1 after surgery. This effect was severe in some rabbits that received bupivicaine; therefore treatment of this entire group with metoclopramide, fluids, and hay was instituted to reverse gut stasis. No significant difference in feed consumption and fecal production was present between the buprenorphine- and meloxicam-treated groups. On the basis of these results, meloxicam appears to be a suitable alternative or adjunct to buprenorphine for alleviating postoperative pain with minimal risk of anorexia and gastrointestinal ileus. PMID:19476717

  19. Messages about methadone and buprenorphine in reality television: a content analysis of celebrity rehab with Dr. Drew.

    PubMed

    Roose, Robert; Fuentes, Liza; Cheema, Mandeep

    2012-08-01

    Medication-assisted treatment for opioid dependence is safe and effective, yet negative perceptions about methadone and buprenorphine may discourage patients from entering treatment. One source of information that may influence viewers' perceptions is television. We performed a content analysis of a popular reality television program on addiction treatment. Although many patients had histories of opioid use, there were no positive messages about methadone or buprenorphine. The two main messages were that they (1) are primarily drugs of abuse, and (2) not acceptable treatment options. These messages reinforce negative stereotypes and may perpetuate stigma. There were multiple missed opportunities to provide evidence-based information. PMID:22587811

  20. Pronociceptive and Antinociceptive Effects of Buprenorphine in the Spinal Cord Dorsal Horn Cover a Dose Range of Four Orders of Magnitude

    PubMed Central

    Gerhold, Katharina J.; Drdla-Schutting, Ruth; Honsek, Silke D.; Forsthuber, Liesbeth

    2015-01-01

    Due to its distinct pharmacological profile and lower incidence of adverse events compared with other opioids, buprenorphine is considered a safe option for pain and substitution therapy. However, despite its wide clinical use, little is known about the synaptic effects of buprenorphine in nociceptive pathways. Here, we demonstrate dose-dependent, bimodal effects of buprenorphine on transmission at C-fiber synapses in rat spinal cord dorsal horn in vivo. At an analgesically active dose of 1500 μg·kg−1, buprenorphine reduced the strength of spinal C-fiber synapses. This depression required activation of spinal opioid receptors, putatively μ1-opioid receptors, as indicated by its sensitivity to spinal naloxone and to the selective μ1-opioid receptor antagonist naloxonazine. In contrast, a 15,000-fold lower dose of buprenorphine (0.1 μg·kg−1), which caused thermal and mechanical hyperalgesia in behaving animals, induced an enhancement of transmission at spinal C-fiber synapses. The ultra-low-dose buprenorphine-induced synaptic facilitation was mediated by supraspinal naloxonazine-insensitive, but CTOP-sensitive μ-opioid receptors, descending serotonergic pathways, and activation of spinal glial cells. Selective inhibition of spinal 5-hydroxytryptamine-2 receptors (5-HT2Rs), putatively located on spinal astrocytes, abolished both the induction of synaptic facilitation and the hyperalgesia elicited by ultra-low-dose buprenorphine. Our study revealed that buprenorphine mediates its modulatory effects on transmission at spinal C-fiber synapses by dose dependently acting on distinct μ-opioid receptor subtypes located at different levels of the neuraxis. PMID:26134641

  1. “Sub is a weird drug:” A Web-based study of lay attitudes about use of buprenorphine to self-treat opioid withdrawal symptoms

    PubMed Central

    Daniulaityte, Raminta; Carlson, Robert; Brigham, Gregory; Cameron, Delroy; Sheth, Amit

    2015-01-01

    Background Illicit use of buprenorphine has increased in the U.S., but our understanding of its use remains limited. This study aims to explore Web-forum discussions about the use of buprenorphine to self-treat opioid withdrawal symptoms. Methods PREDOSE, a novel Semantic Web platform, was used to extract relevant posts from a Web-forum that allows free discussions on illicit drugs. First, we extract information about the total number of buprenorphine-related posts per year between 2005 and 2013. Second, PREDOSE was used to identify all posts that potentially contained discussions about buprenorphine and opioid withdrawal. A total number of 1,217 posts that contained these terms were extracted and entered into NVivo data base. A random sample of 404 (33%) posts was selected and content analyzed. Results Buprenorphine-related posts increased over time, peaking in 2011. The posts were about equally divided between those that expressed positive and negative views about the effectiveness of buprenorphine in relieving withdrawal symptoms. Web-forum participants emphasized that buprenorphine’s effectiveness may become compromised because of the “size of a person habit,” and/or when users repeatedly switch back and forth between buprenorphine and other illicit opioids. Most posts reported use of significantly lower amounts of buprenorphine ( 2 mg) than doses used in standard treatment. Concomitant use of other psychoactive substances was also commonly reported, which may present significant health risks. Conclusions Our findings highlight the usefulness of Web-based data in drug abuse research and add new information about lay beliefs about buprenorphine that may help inform prevention and policy measures. PMID:26009867

  2. Interdisciplinary index of prosthodontic/substitution orthodontic treatment need for patients with missing teeth.

    PubMed

    Janiszewska-Olszowska, Joanna; Grocholewicz, Katarzyna; Czerniawska-Kliman, Luiza

    2015-01-01

    The need for treatment in cases of missing teeth may result from aesthetic demands or functional impairment, although tooth loss itself does not necessarily constitute a need for prosthetic replacement. In selected cases, restorative treatment can be replaced by tooth autotransplantation or substitution orthodontic treatment. The authors have tried to make an index based not on missing particular teeth, but on the presence of spacing requiring restoration. An attempt has been made to categorize the restorative treatment need. Orthodontic treatment was considered, when it could completely eliminate the need for prosthetic treatment. The proposed classification could be used for assessing eligibility for public refund of restorative or substitution orthodontic treatment, as well as to motivate the patients to have restorations. It should be an individual approach-based decision, which treatment: orthodontic substitution tooth movement or prosthodontic is more cost-effective for the rest of the patient's life. PMID:27116858

  3. Effects of voluntarily-ingested buprenorphine on plasma corticosterone levels, body weight, water intake, and behaviour in permanently catheterised rats.

    PubMed

    Goldkuhl, Renée; Hau, Jann; Abelson, Klas S P

    2010-01-01

    This study investigated the peri- and postoperative effect of pre-emptive analgesia through voluntary ingestion of buprenorphine in Nutella, in male Sprague-Dawley rats. An arterial catheter was inserted and the rats were connected to an automated blood sampling device (AccuSampler). Blood samples were drawn up to 18 h after surgery and the plasma concentrations of corticosterone were quantified. Postoperative changes in water intake and body weight were recorded, and the behaviour of the rats was analysed during two 30-min periods. Pre-emptive oral buprenorphine treatment reduced the plasma corticosterone levels in the postoperative period, compared to controls treated with local anaesthetics. Buprenorphine-treated rats consumed more water and maintained body weight better. Behavioural observations indicated that buprenorphine changed the behaviour in non-operated rats but there was no difference in the operated rats. The present study strengthens the hypothesis that pre-emptive oral buprenorphine in Nutella is suitable for treatment of postoperative pain in rats. PMID:20363983

  4. Clients' perceptions of opioid substitution treatment: an input to improving the quality of treatment.

    PubMed

    Deering, Daryle; Horn, Jacqueline; Frampton, Christopher M A

    2012-08-01

    Despite the emphasis on providing high quality mental health and addiction treatment, there has been relatively little consideration given to examining clients' perceptions of addiction treatment (consumer satisfaction) as a quality improvement strategy. The present article reports on a survey of a representative sample of 93 clients receiving opioid substitution treatment (OST). Employed participants reported higher treatment satisfaction and a pattern of positive associations was found between satisfaction and general health, mental health, social functioning, lower methadone doses, and participants' ratings of their treatment progress. Lower satisfaction was associated with higher frequency of benzodiazepine use, and, for women, longer treatment duration. Māori participants rated their treatment progress as lower than that of non-Māori. Results strongly endorse recording participants' comments to provide a deeper understanding of survey item ratings. The study findings highlight the need for a research focus on the roles of mental health and other registered nurses who work with people receiving OST in specialist service and primary care settings, and endorse a partnership approach to future research in this area. The pattern of findings arising from this study suggests key strategies for improving the flexibility and client responsiveness of OST. PMID:22564199

  5. Oral self-administration of buprenorphine in the diet for analgesia in mice.

    PubMed

    Molina-Cimadevila, M J; Segura, S; Merino, C; Ruiz-Reig, N; Andrés, B; de Madaria, E

    2014-04-23

    Postsurgical oral self-administration of analgesics in rodents is an interesting technique of providing analgesia, avoiding the negative effects of manipulation. Several strategies, using gelatin or nutella, have already been described. However, rodents require some habituation period to reach a good intake because of their neophobic behavior. The current study aimed to explore whether buprenorphine when mixed with an extruded diet offers a potential treatment option in the pain management of mice using a triple approach: by measuring the spontaneous intake in healthy animals; by using the hot-plate test; and finally by assessing the drug's ability to provide postoperative analgesia in a surgical intervention of moderate severity (intra-utero electroporation). Mice consumed during 20 hours, similar amounts of extruded diet alone, mixed with glucosaline, and mixed with buprenorphine (0.03 mg per pellet) or meloxicam (0.25 mg per pellet) both of which were diluted in glucosaline, showing that no neophobia was associated with these administrations. Relative increase from baseline latency (% maximal possible effect) in the hot-plate test at 20 h of administration was significantly higher for oral buprenorphine in diet 0.03 mg/pellet, and diet 0.15 mg/pellet, compared with placebo and no differences were found between those oral administrations and subcutaneous buprenorphine 0.1 mg/kg measured 3 h later. The treatment was also effective in attenuating the reductions in food consumption and body weight that occur after surgery. These data suggest that providing buprenorphine with the diet is a feasible and effective way of self-administration of analgesia in mice and does not cause neophobia and may easily contribute to the refinement of surgical procedures. PMID:24759572

  6. Effects of Dexmedetomidine and Ketamine–Dexmedetomidine with and without Buprenorphine on Corticoadrenal Function in Rabbits

    PubMed Central

    González-Gil, Alfredo; Villa, Alberto; Millán, Pilar; Martínez-Fernández, Leticia; Illera, Juan Carlos

    2015-01-01

    Anesthetics may influence adrenal function and consequently alter serum glucocorticoid concentrations, leading to erroneous interpretations of results from anesthetized rabbits. However, decreases in glucocorticoid concentrations may be advantageous in protocols designed to minimize the stress response to surgery. This study characterized the variations in adrenocortical function based on changes in corticosterone and cortisol levels after various doses and combinations of dexmedetomidine, ketamine, and buprenorphine. Each rabbit received all treatments with a minimal interexperiment interval of 10 d. Rabbits were allocated to 7 groups (n = 10 per group) and received either 1 mL saline solution; dexmedetomidine at 0.05, 0.15, or 0.25 mg/kg; ketamine (35 mg/kg) and dexmedetomidine (0.25 mg/kg) without or with buprenorphine (0.03 mg/kg); or ketamine (35 mg/kg) and buprenorphine (0.03 mg/kg). Blood was sampled before drug administration and at 10, 30, 60, and 120 min and 24 h afterward. Serum glucocorticoid levels fell in all treatment groups except the one receiving ketamine–dexmedetomidine; in that group, serum glucocorticoids increased. Rabbits that received ketamine–dexmedetomidine–buprenorphine had the lowest serum glucocorticoid levels overall. In conclusion, dexmedetomidine reduces glucocorticoid secretion in rabbits but, when combined with ketamine, increases corticosterone and cortisol levels as well as heart and respiratory rates. The addition of buprenorphine to the ketamine–dexmedetomidine mixture reduces serum glucocorticoid levels. The influence of anesthetic drugs should be considered when designing a protocol to minimize the glucocorticoid response to surgery or when measuring glucocorticoid levels in rabbits. PMID:26045456

  7. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) contaminated with an inorganic metal-bearing hazardous waste; (3) The waste, at point of generation, has... restricted waste or the residual from treatment of a restricted waste as a substitute for adequate treatment... specified in § 268.40 as the treatment standard, or unless the waste is a D003 reactive cyanide...

  8. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) contaminated with an inorganic metal-bearing hazardous waste; (3) The waste, at point of generation, has... restricted waste or the residual from treatment of a restricted waste as a substitute for adequate treatment... specified in § 268.40 as the treatment standard, or unless the waste is a D003 reactive cyanide...

  9. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) contaminated with an inorganic metal-bearing hazardous waste; (3) The waste, at point of generation, has... restricted waste or the residual from treatment of a restricted waste as a substitute for adequate treatment... specified in § 268.40 as the treatment standard, or unless the waste is a D003 reactive cyanide...

  10. Substance use and quality of life over 12 months among buprenorphine maintenance-treated and methadone maintenance-treated heroin-addicted patients.

    PubMed

    Maremmani, Icro; Pani, Pier Paolo; Pacini, Matteo; Perugi, Giulio

    2007-07-01

    The purpose of this study was to investigate the effects of methadone treatment and buprenorphine treatment on retention in treatment, urine drug testing results, psychiatric status, social adjustment, and quality of life among patients involved in long-term treatment with the cited medications. Two hundred thirteen patients (106 on buprenorphine treatment and 107 on methadone treatment) were enrolled in this open study at the 3rd month of their treatment and followed up until the 12th month; those who left the program before the end of the 3rd month of their treatment were not included in the study sample. The results of this study show statistically significant improvements in opioid use, psychiatric status, and quality of life between the 3rd and 12th months for both medications. This study suggests the long-term efficacy of methadone treatment and buprenorphine treatment on symptoms of opioid addiction and quality of life. PMID:17588494

  11. Substitutes for Bear Bile for the Treatment of Liver Diseases: Research Progress and Future Perspective

    PubMed Central

    Li, Sha; Tan, Hor Yue; Wang, Ning; Hong, Ming; Li, Lei; Cheung, Fan; Feng, Yibin

    2016-01-01

    Bear bile has been a well-known Chinese medicine for thousands of years. Because of the endangered species protection, the concept on substitutes for bear bile was proposed decades ago. Based on their chemical composition and pharmacologic actions, artificial bear bile, bile from other animals, synthetic compounds, and medicinal plants may be the promising candidates to replace bear bile for the similar therapeutic purpose. Accumulating research evidence has indicated that these potential substitutes for bear bile have displayed the same therapeutic effects as bear bile. However, stopping the use of bear bile is a challenging task. In this review, we extensively searched PubMed and CNKI for literatures, focusing on comparative studies between bear bile and its substitutes for the treatment of liver diseases. Recent research progress in potential substitutes for bear bile in the last decade is summarized, and a strategy for the use of substitutes for bear bile is discussed carefully. PMID:27087822

  12. Substitutes for Bear Bile for the Treatment of Liver Diseases: Research Progress and Future Perspective.

    PubMed

    Li, Sha; Tan, Hor Yue; Wang, Ning; Hong, Ming; Li, Lei; Cheung, Fan; Feng, Yibin

    2016-01-01

    Bear bile has been a well-known Chinese medicine for thousands of years. Because of the endangered species protection, the concept on substitutes for bear bile was proposed decades ago. Based on their chemical composition and pharmacologic actions, artificial bear bile, bile from other animals, synthetic compounds, and medicinal plants may be the promising candidates to replace bear bile for the similar therapeutic purpose. Accumulating research evidence has indicated that these potential substitutes for bear bile have displayed the same therapeutic effects as bear bile. However, stopping the use of bear bile is a challenging task. In this review, we extensively searched PubMed and CNKI for literatures, focusing on comparative studies between bear bile and its substitutes for the treatment of liver diseases. Recent research progress in potential substitutes for bear bile in the last decade is summarized, and a strategy for the use of substitutes for bear bile is discussed carefully. PMID:27087822

  13. Use of Naltrexone to Treat Opioid Addiction in a Country in Which Methadone and Buprenorphine Are Not Available

    PubMed Central

    Zvartau, Edwin; Woody, George

    2011-01-01

    Opioid dependence is one of the most severe drug dependencies. Naltrexone is a medication that completely blocks the subjective and other effects of opioids and, when administered to detoxified opioid addicts and taken as directed, prevents relapse and helps maintain abstinence. The major problem with naltrexone is poor compliance, particularly in countries in which there is a treatment alternative based on substitution of illicit opioids such as heroin with orally administered opioid agonists (methadone) or partial agonist/antagonists (buprenorphine). In Russia, substitution therapy is forbidden by law, and naltrexone is the only available pharmacotherapy for heroin dependence. Due to the lack of alternatives to naltrexone and stronger family control of compliance (adherence), naltrexone is more effective for relapse prevention and abstinence stabilization in Russia than in Western countries. Long-acting, sustained-release formulations (injectable and implantable) seem particularly effective compared with oral formulations. This article summarizes the results of studies conducted in Russia during the past 10 years that demonstrate these points. PMID:20640538

  14. Quantitation of Buprenorphine, Norbuprenorphine, Buprenorphine Glucuronide, Norbuprenorphine Glucuronide, and Naloxone in Urine by LC-MS/MS.

    PubMed

    Marin, Stephanie J; McMillin, Gwendolyn A

    2016-01-01

    Buprenorphine is an opioid drug that has been used to treat opioid dependence on an outpatient basis, and is also prescribed for managing moderate to severe pain. Some formulations of buprenorphine also contain naloxone to discourage misuse. The major metabolite of buprenorphine is norbuprenorphine. Both compounds are pharmacologically active and both are extensively metabolized to their glucuronide conjugates, which are also active metabolites. Direct quantitation of the glucuronide conjugates in conjunction with free buprenorphine, norbuprenorphine, and naloxone in urine can distinguish compliance with prescribed therapy from specimen adulteration intended to mimic compliance with prescribed buprenorphine. This chapter quantitates buprenorphine, norbuprenorphine, their glucuronide conjugates and naloxone directly in urine by liquid chromatography tandem mass spectrometry (LC-MS/MS). Urine is pretreated with formic acid and undergoes solid phase extraction (SPE) prior to analysis by LC-MS/MS. PMID:26660175

  15. The emerging buprenorphine epidemic in the United States.

    PubMed

    Wish, Eric D; Artigiani, Erin; Billing, Amy; Hauser, Wanda; Hemberg, Jordana; Shiplet, Myron; DuPont, Robert L

    2012-01-01

    The authors sampled for expanded drug testing of 1,061 urine specimens collected by Maryland Division of Parole and Probation staff. They found an increase in the percentage of individuals testing positive for buprenorphine and found that these specimens often contained other drugs, suggesting misuse. Subsequent interviews with 15 probationers and parolees in Baltimore, Maryland, showed wide-scale availability of buprenorphine on the street and in prisons. Medical examiners and drug testing programs should immediately initiate routine testing for buprenorphine to track a possible outbreak of buprenorphine diversion and misuse. Physician education programs should redouble their efforts to teach strategies to deter diversion and misuse of the drug. PMID:22356664

  16. The pharmacodynamic and pharmacokinetic profile of intranasal crushed buprenorphine and buprenorphine/naloxone tablets in opioid abusers

    PubMed Central

    Middleton, L.S.; Nuzzo, P.A.; Lofwall, M.R.; Moody, D.E.; Walsh, S.L.

    2011-01-01

    Aims Sublingual buprenorphine and buprenorphine/naloxone are efficacious opioid dependence pharmacotherapies, but there are reports of their diversion and misuse by the intranasal route. The study objectives were to characterize and compare their intranasal pharmacodynamic and pharmacokinetic profiles. Design A randomized, double-blind, placebo-controlled, crossover study. Setting An in-patient research unit at the University of Kentucky. Participants Healthy adults (n=10) abusing, but not physically dependent on, intranasal opioids. Measurements Six sessions (72 hours apart) tested five intranasal doses [0/0, crushed buprenorphine (2, 8 mg), crushed buprenorphine/naloxone (2/0.5, 8/2 mg)] and one intravenous dose (0.8 mg buprenorphine/0.2 mg naloxone for bioavailability assessment). Plasma samples, physiological, subject- and observer-rated measures were collected before and for up to 72 hours after drug administration. Findings Both formulations produced time- and dose-dependent increases on subjective and physiological mu-opioid agonist effects (e.g. ‘liking’, miosis). Subjects reported higher subjective ratings and street values for 8 mg compared to 8/2 mg, but these differences were not statistically significant. No significant formulation differences in peak plasma buprenorphine concentration or time-course were observed. Buprenorphine bioavailability was 38–44% and Tmax was 35–40 minutes after all intranasal doses. Naloxone bioavailability was 24% and 30% following 2/0.5 and 8/2 mg, respectively. Conclusions It is difficult to determine if observed differences in abuse potential between intranasal buprenorphine and buprenorphine/naloxone are clinically relevant at the doses tested. Greater bioavailability and faster onset of pharmacodynamic effects compared to sublingual administration suggests a motivation for intranasal misuse in non-dependent opioid abusers. However, significant naloxone absorption from intranasal buprenorphine

  17. Double successful buprenorphine/naloxone induction to facilitate cardiac transplantation in an iatrogenically opiate-dependent patient.

    PubMed

    Rodgman, Christopher; Pletsch, Gayle

    2012-06-01

    Buprenorphine/naloxone is used for the treatment of opioid dependence. In the following case, a potential use for the medication combination is explored in the arena of transplant surgery. Psychiatry was consulted for a 29-year-old woman with iatrogenic opioid dependence after bilateral ventricular assist device placement for congenital cardiomyopathy. Her ejection fraction was less than 15% and she was considered a poor candidate for transplant due to drug-seeking behaviors. We transitioned her onto buprenorphine/naloxone to prevent abuse and control symptoms, qualifying her for cardiac transplant. After transplant, we coordinated care with cardiothoracic surgeons to restart buprenorphine/naloxone, and the patient has been stable for 8 months. PMID:22456493

  18. Buprenorphine/naloxone therapy for opioid refractory neuropathic pain following traumatic amputation: a case series.

    PubMed

    Licina, Lauren; Hamsher, Carlyle; Lautenschager, Karl; Dhanjal, Sandeep; Williams, Necia; Spevak, Christopher

    2013-07-01

    Phantom limb pain is a common consequence of limb amputation and is prevalent among the service members sustaining traumatic battlefield limb injuries during the conflicts in Iraq and Afghanistan. Current treatment to relieve phantom limb pain consists of physical, behavioral, and medical modalities including opioids and adjunct medications. Treatment failure resulting in persistent pain and disability may result. This case series describes four previously healthy service members who developed phantom limb pain following traumatic amputation successfully treated with buprenorphine/naloxone after failing traditional treatment. This is the first reported case series of patients expressing improved pain control with decreased frequency of phantom limb pain with the use of buprenorphine/naloxone instead of traditional opioid agonists. PMID:23820366

  19. 40 CFR 148.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... for treatment. 148.3 Section 148.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) HAZARDOUS WASTE INJECTION RESTRICTIONS General § 148.3 Dilution prohibited as a substitute for treatment. The prohibition of § 268.3 shall apply to owners or operators...

  20. 40 CFR 148.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... for treatment. 148.3 Section 148.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) HAZARDOUS WASTE INJECTION RESTRICTIONS General § 148.3 Dilution prohibited as a substitute for treatment. The prohibition of § 268.3 shall apply to owners or operators...

  1. 40 CFR 148.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... for treatment. 148.3 Section 148.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) HAZARDOUS WASTE INJECTION RESTRICTIONS General § 148.3 Dilution prohibited as a substitute for treatment. The prohibition of § 268.3 shall apply to owners or operators...

  2. 40 CFR 148.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... for treatment. 148.3 Section 148.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) HAZARDOUS WASTE INJECTION RESTRICTIONS General § 148.3 Dilution prohibited as a substitute for treatment. The prohibition of § 268.3 shall apply to owners or operators...

  3. Tuberculosis treatment and risk of stavudine substitution in first line antiretroviral therapy

    PubMed Central

    Westreich, Daniel J.; Sanne, Ian; Maskew, Mhairi; Malope-Kgokong, Babatyi; Conradie, Francesca; Majuba, Pappie; Funk, Michele Jonsson; Kaufman, Jay S.; Van Rie, Annelies; MacPhail, Patrick

    2009-01-01

    Background Treatment for tuberculosis (TB) is common among individuals receiving stavudine-containing highly active antiretroviral therapy (HAART), but the effect of TB treatment on stavudine toxicity has received little attention. We estimated the effect of TB treatment on risk of stavudine substitution among individuals receiving first-line HAART. Methods We evaluated a cohort of 7,066 patients who initiated HAART between April 2004 and March 2007 in Johannesburg, South Africa. Three exposure categories were considered: ongoing TB treatment at HAART initiation; concurrent initiation of TB treatment and HAART; incident TB treatment after HAART initiation. The outcome was single-drug stavudine substitution. Adjusted hazard ratios (aHRs) were estimated using marginal structural models to control for confounding, loss to follow-up, and competing risks. Results Individuals with ongoing and concurrent TB treatment were at increased risk of stavudine substitution, irrespective of stavudine dose. For ongoing TB treatment, aHR was 3.18 (95% confidence interval [CI] 1.82-5.56) in the first two months of HAART, 2.51 (95% CI 1.77-3.54) in months 3-6, and 1.19 (95% CI 0.94-1.52) thereafter. For concurrent TB treatment, aHR was 6.60 (95% CI 3.03-14.37) in the first two months,1.88 (95% CI 0.87-4.09) in months 3-6, and 1.07 (95% CI 0.65-1.76) thereafter. There was no effect of incident TB on stavudine substitution risk. Conclusions Risk of stavudine substitution was increased among patients receiving TB treatment, especially soon after HAART initiation. In settings where alternative antiretroviral drugs are available, initiation of stavudine in patients receiving TB treatment may need to be reconsidered. PMID:19385733

  4. A non-rewarding, non-aversive buprenorphine/naltrexone combination attenuates drug-primed reinstatement to cocaine and morphine in rats in a conditioned place preference paradigm.

    PubMed

    Cordery, Sarah F; Taverner, Alistair; Ridzwan, Irna E; Guy, Richard H; Delgado-Charro, M Begoña; Husbands, Stephen M; Bailey, Christopher P

    2014-07-01

    Concurrent use of cocaine and heroin is a major public health issue with no effective relapse prevention treatment currently available. To this purpose, a combination of buprenorphine and naltrexone, a mixed very-low efficacy mu-opioid receptor agonist/kappa-opioid receptor antagonist/nociceptin receptor agonist, was investigated. The tail-withdrawal and the conditioned place preference (CPP) assays in adult Sprague Dawley rats were used to show that naltrexone dose-dependently blocked the mu-opioid receptor agonism of buprenorphine. Furthermore, in the CPP assay, a combination of 0.3 mg/kg buprenorphine and 3.0 mg/kg naltrexone was aversive. A combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone was neither rewarding nor aversive, but still possessed mu-opioid receptor antagonist properties. In the CPP extinction and reinstatement method, a combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone completely blocked drug-primed reinstatement in cocaine-conditioned rats (conditioned with 3 mg/kg cocaine, drug prime was 3 mg/kg cocaine) and attenuated drug-primed reinstatement in morphine-conditioned rats (conditioned with 5 mg/kg morphine, drug prime was 1.25 mg/kg morphine). These data add to the growing evidence that a buprenorphine/naltrexone combination may be protective against relapse in a polydrug abuse situation. PMID:23240906

  5. The impact of recent cocaine use on plasma levels of methadone and buprenorphine in patients with and without HIV-infection.

    PubMed

    Tetrault, Jeanette M; McCance-Katz, Elinore F; Moody, David E; Fiellin, David A; Lruie, Bonnie S; DInh, An T; Fiellin, Lynn E

    2015-04-01

    Cocaine decreases methadone and buprenorphine plasma concentrations. HIV infection and/or antiretroviral medication use may impact these relationships. We sought to determine the association between recent cocaine use and methadone and buprenorphine concentrations in HIV-infected and uninfected subjects in clinical care. R- and S-methadone or buprenorphine and norbuprenorphine concentrations were assessed at 0.5, 1, 2, and 24 hours after dosing in subjects with confirmed cocaine use and abstinence. We compared methadone and buprenorphine concentrations for cocaine use vs. abstinence, by HIV status in 16 subjects receiving methadone (6 HIV-infected) and 17 receiving buprenorphine (8 HIV-infected). With recent cocaine use, peak R-methadone (244 vs. 297 ng/mL, p = 0.03) and peak S-methadone (285 vs. 339 ng/mL); p = 0.03 concentrations were lower in HIV-uninfected subjects only. Peak buprenorphine and norbuprenorphine concentrations were unchanged regardless of cocaine use or HIV status. Cocaine may decrease methadone concentrations in HIV-uninfected subjects. HIV infection or its treatment may attenuate cocaine's effect on methadone. PMID:25480096

  6. Comparison of pethidine, buprenorphine and ketoprofen for postoperative analgesia after ovariohysterectomy in the cat.

    PubMed

    Slingsby, L S; Waterman-Pearson, A E

    1998-08-15

    Sixty cats which underwent an ovariohysterectomy were randomly allocated into four treatment groups. One group (controls) received no analgesics postoperatively, and the others received either a single dose of buprenorphine (0.006 mg/kg) intramuscularly, or pethidine (5 mg/kg) intramuscularly, or ketoprofen (2 mg/kg) subcutaneously. The analgesia obtained after each treatment was assessed by three measures. There were significant differences between the groups both for the requirement for intervention analgesia (P = 0.0008) and for the overall clinical assessment (P = 0.0003) with ketoprofen requiring least intervention analgesia and having the best overall clinical assessment, followed by buprenorphine then pethidine. The control group required the most intervention analgesia and had the worst overall clinical assessment. Visual analogue scale scoring for pain produced significant differences between the groups from one hour after the operation, with the cats which were given ketoprofen tending to have lower pain scores than the other groups. PMID:9762758

  7. Home- versus office-based buprenorphine inductions for opioid-dependent patients

    PubMed Central

    Sohler, Nancy L.; Li, Xuan; Kunins, Hillary V.; Sacajiu, Galit; Giovanniello, Angela; Whitley, Susan; Cunningham, Chinazo O.

    2010-01-01

    Recent legislation permits the treatment of opioid-dependent patients with buprenorphine in the primary care setting, opening doors for the development of new treatment models for opioid dependence. We modified national buprenorphine treatment guidelines to emphasize patient self-management by giving patients the opportunity to choose to have buprenorphine inductions at home or the physician’s office. We examined whether patients who had home-based inductions achieved greater 30-day retention than patients who had traditional office-based inductions in a study of 115 opioid-dependent patients treated in an inner-city health center. Retention was similar in both groups: 50 (78.1%) in office-based group versus 40 (78.4%) in home-based group, p = .97. Several patient characteristics were associated with choosing office- versus home-based inductions, which likely influenced these results. We conclude that opioid dependence can be successfully managed in the primary care setting. Approaches that encourage patient involvement in treatment for opioid dependence can be beneficial. PMID:19801178

  8. Bethanechol for buprenorphine-related urinary hesitancy: a case series.

    PubMed

    Varma, Anjali; Smigiel, Joseph; Eck, Nancy; Brooks, Stephanie

    2011-09-01

    Constipation is a well-known side effect of buprenorphine, but urinary hesitancy is less frequently discussed and may go unrecognized. Reported are the 2 cases of men older than 50 years who experienced disabling urinary hesitancy with buprenorphine and naloxone combination (suboxone) and were successfully treated with bethanechol, a cholinergic medication. PMID:21844838

  9. A Review of Buprenorphine Diversion and Misuse: The Current Evidence Base and Experiences from Around the World

    PubMed Central

    Lofwall, Michelle R.; Walsh, Sharon L.

    2014-01-01

    Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy (OBOT) has rapidly expanded in the United States and abroad, and, with this increase in medication availability, there have been increasing concerns about its diversion, misuse and related harms. This narrative review defines the behaviors of diversion and misuse, examines how the pharmacology of buprenorphine alone and in combination with naloxone influence its abuse liability, and describes the epidemiological data on buprenorphine diversion and intravenous misuse, risk factors for its intravenous misuse and the unintended consequences of misuse and diversion. Physician practices to prevent, screen for, and therapeutically respond to these behaviors, which are a form of medication non-adherence, are discussed and gaps in knowledge are identified. OBOT experiences from other countries that have varied health care systems, public policies, and access to addiction treatment are shared in order to make clear that diversion and misuse occur across the world in various contexts, for many different reasons, and are not limited to buprenorphine. Comparisons are made with other opioids with known abuse liability as well as medications with no known abuse. The objective is to facilitate understanding of diversion and misuse so that all factors influencing their expression (patient and provider characteristics and public policy) can be appreciated within a framework that also recognizes the benefits of addiction treatment. With this comprehensive perspective, further careful work can help determine how to minimize these behaviors without eroding the current benefits realized through improved addiction treatment access and expansion. PMID:25221984

  10. Epidural buprenorphine or morphine for the relief of head and neck cancer pain.

    PubMed Central

    Hashimoto, Y.; Utsumi, T.; Tanioka, H.; Rigor, B. M.

    1991-01-01

    We present three cases in which epidural buprenorphine or morphine was used for intractable cancer pain of the head and neck. Excellent pain relief and minimal side effects offered by epidural opioids were of significant benefit. The use of epidural opioids prior to the administration of high doses of oral morphine may be the treatment of choice for pain from malignancy of the head and neck, especially when there is tumor extension or distant metastasis. PMID:1811431

  11. Cocaine Use Reduction with Buprenorphine (CURB): Rationale, design, and methodology☆

    PubMed Central

    Mooney, Larissa J.; Nielsen, Suzanne; Saxon, Andrew; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Stablein, Don; McCormack, Jennifer; Lindblad, Robert; Ling, Walter

    2013-01-01

    Background Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study. Methods This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. Conclusions This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP. PMID:23159524

  12. Do methadone and buprenorphine have the same impact on psychopathological symptoms of heroin addicts?

    PubMed Central

    2011-01-01

    Background The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months. Methods Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period. Results No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology. Conclusions Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too. PMID:21569624

  13. Change in symptoms of erectile dysfunction in depressed men initiating buprenorphine therapy☆

    PubMed Central

    Cioe, Patricia A.; Anderson, Bradley J.; Stein, Michael D.

    2014-01-01

    Aims The aim of this study is to describe the change in erectile dysfunction (ED) symptoms in the first 12 weeks of outpatient buprenorphine therapy. Background Erectile dysfunction is highly prevalent in men who use illicit opioids when compared with the general population. To date, no study has examined ED symptoms over time in men initiating buprenorphine therapy for opioid dependence. Methods A randomized, double blind, placebo-controlled trial was conducted to determine whether escitalopram treatment of depressive symptoms begun 1 week prior to buprenorphine induction would improve treatment retention. Male patients completed the International Index of Erectile Function scale at baseline prior to induction and monthly thereafter. A score of 25 or less on the erectile function domain (range 1–30) is considered indicative of erectile dysfunction. Findings A total of 111 male subjects enrolled: mean age 38.5 (± 9.7) years, 80.1% non-Hispanic Caucasian; 67.3% reported heroin as their opioid of choice. Mean IIEF at baseline was 20.4 (± 10.5). At baseline, 44.1% of the entire cohort had erectile dysfunction; among those who identified as sexually active at baseline, 26.1% had ED. Baseline erectile function was inversely and significantly correlated with age (r = −.27, p = .006), but was not associated significantly with race, heroin use, years of opioid use, smoking, or hazardous use of alcohol. Compared to baseline, mean erectile function was significantly improved (p = .001) at 3 months, and sexual desire (p = .002) improved significantly at both 2- and 3-month assessments. Conclusion Erectile dysfunction is highly prevalent in depressed males using illicit opioids. Men who remain in buprenorphine treatment for 3 months show improvement in erectile function and sexual desire. PMID:23891461

  14. Effects of Buprenorphine and Meloxicam Analgesia on Induced Cerebral Ischemia in C57BL/6 Male Mice

    PubMed Central

    Jacobsen, Kirsten R; Fauerby, Natasha; Raida, Zindy; Kalliokoski, Otto; Hau, Jann; Johansen, Flemming F; Abelson, Klas SP

    2013-01-01

    Laboratory mice constitute an extensively used model to study the pathologic and functional outcomes of cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) model requires surgical intervention, which potentially can result in postsurgical pain and stress. In the present study, we investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects were brief and seen only during the treatment period. Fecal corticosterone metabolites did not differ significantly between the groups. In the present study, buprenorphine treatment did not alter infarction volume when compared with that of mice that did not receive analgesia. In contrast, meloxicam treatment significantly reduced infarct volume and may be a confounder if used as an analgesic during MCAO surgery. Furthermore, investigation of behavioral profiles by using an automated behavioral scoring system showed that rearing and sniffing behaviors decreased as infarct volume increased. This suggests that studies of exploratory behavior may aid in developing new markers of short-term stroke-related behavioral deficiencies in laboratory mice. PMID:23582417

  15. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    PubMed Central

    Soltani, Ghasem; Khorsand, Mahmood; Shamloo, Alireza Sepehri; Jarahi, Lida; Zirak, Nahid

    2015-01-01

    Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA) with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5µg/kg sublingually) and morphine (0.2mg/kg intravenously). Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes), and in the ward (at 3, 6 and 12 hours). SPSS version 19 software was used for data analysis and the significance level was set at P<0.05. Results: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics. Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P<0.001). Postoperative mean heart rate in the buprenorphine group was four beats lower than the morphine group (P<0.001). Also, in the buprenorphine 48.6% and in the morphine group 86.7% of cases were conscious in recovery (P=0.001) with a higher rate of pruritus in the latter group (P=0.001). Conclusion: Sublingual buprenorphine administration before anesthesia induction in closed reduction surgery can lead to better postoperative pain control in comparison to intravenous morphine. Due to simple usage and longer postoperative sedation, sublingual buprenorphine is recommended as a suitable drug in closed reduction surgery

  16. Assessment of Drug-Drug Interactions between Daclatasvir and Methadone or Buprenorphine-Naloxone

    PubMed Central

    Wang, R.; Luo, W.-L.; Wastall, P.; Kandoussi, H.; DeMicco, M.; Bruce, R. D.; Hwang, C.; Bertz, R.; Bifano, M.

    2015-01-01

    Hepatitis C virus (HCV) infection is common among people who inject drugs, including those managed with maintenance opioids. Pharmacokinetic interactions between opioids and emerging oral HCV antivirals merit evaluation. Daclatasvir is a potent pangenotypic inhibitor of the HCV NS5A replication complex recently approved for HCV treatment in Europe and Japan in combination with other antivirals. The effect of steady-state daclatasvir (60 mg daily) on stable plasma exposure to oral opioids was assessed in non-HCV-infected subjects receiving methadone (40 to 120 mg; n = 14) or buprenorphine plus naloxone (8 to 24 mg plus 2 to 6 mg; n = 11). No relevant interaction was inferred if the 90% confidence interval (CI) of the geometric mean ratio (GMR) of opioid area under the plasma concentration-time curve over the dosing interval (AUCτ) or maximum concentration in plasma (Cmax) with versus without daclatasvir was within literature-derived ranges of 0.7 to 1.43 (R- and S-methadone) or 0.5 to 2.0 (buprenorphine and norbuprenorphine). Dose-normalized AUCτ for R-methadone (GMR, 1.08; 90% CI, 0.94 to 1.24), S-methadone (1.13; 0.99 to 1.30), and buprenorphine (GMR, 1.37; 90% CI, 1.24 to 1.52) were within the no-effect range. The norbuprenorphine AUCτ was slightly elevated in the primary analysis (GMR, 1.62; 90% CI, 1.30 to 2.02) but within the no-effect range in a supplementary analysis of all evaluable subjects. Dose-normalized Cmax for both methadone enantiomers, buprenorphine and norbuprenorphine, were within the no-effect range. Standardized assessments of opioid pharmacodynamics were unchanged throughout daclatasvir administration with methadone or buprenorphine. Daclatasvir pharmacokinetics were similar to historical data. Coadministration of daclatasvir and opioids was generally well tolerated. In conclusion, these data suggest that daclatasvir can be administered with buprenorphine or methadone without dose adjustments. PMID:26124175

  17. Assessment of drug-drug interactions between daclatasvir and methadone or buprenorphine-naloxone.

    PubMed

    Garimella, T; Wang, R; Luo, W-L; Wastall, P; Kandoussi, H; DeMicco, M; Bruce, R D; Hwang, C; Bertz, R; Bifano, M

    2015-09-01

    Hepatitis C virus (HCV) infection is common among people who inject drugs, including those managed with maintenance opioids. Pharmacokinetic interactions between opioids and emerging oral HCV antivirals merit evaluation. Daclatasvir is a potent pangenotypic inhibitor of the HCV NS5A replication complex recently approved for HCV treatment in Europe and Japan in combination with other antivirals. The effect of steady-state daclatasvir (60 mg daily) on stable plasma exposure to oral opioids was assessed in non-HCV-infected subjects receiving methadone (40 to 120 mg; n = 14) or buprenorphine plus naloxone (8 to 24 mg plus 2 to 6 mg; n = 11). No relevant interaction was inferred if the 90% confidence interval (CI) of the geometric mean ratio (GMR) of opioid area under the plasma concentration-time curve over the dosing interval (AUCτ) or maximum concentration in plasma (C max) with versus without daclatasvir was within literature-derived ranges of 0.7 to 1.43 (R- and S-methadone) or 0.5 to 2.0 (buprenorphine and norbuprenorphine). Dose-normalized AUCτ for R-methadone (GMR, 1.08; 90% CI, 0.94 to 1.24), S-methadone (1.13; 0.99 to 1.30), and buprenorphine (GMR, 1.37; 90% CI, 1.24 to 1.52) were within the no-effect range. The norbuprenorphine AUCτ was slightly elevated in the primary analysis (GMR, 1.62; 90% CI, 1.30 to 2.02) but within the no-effect range in a supplementary analysis of all evaluable subjects. Dose-normalized C max for both methadone enantiomers, buprenorphine and norbuprenorphine, were within the no-effect range. Standardized assessments of opioid pharmacodynamics were unchanged throughout daclatasvir administration with methadone or buprenorphine. Daclatasvir pharmacokinetics were similar to historical data. Coadministration of daclatasvir and opioids was generally well tolerated. In conclusion, these data suggest that daclatasvir can be administered with buprenorphine or methadone without dose adjustments. PMID:26124175

  18. The animal pharmacology of buprenorphine, an oripavine analgesic agent.

    PubMed

    Cowan, A; Doxey, J C; Harry, E J

    1977-08-01

    1. The general pharmacology of buprenorphine, a potent analgesic agent derived from oripavine, is described. 2. After cute administration of buprenorphine, the spontaneous locomotor activity of mice was increased; rats displayed stereotyped licking and biting movements; behavioural depression was marked in guinea-pigs but mild in rhesus monkeys. The behaviour of cats was unchanged. 3. In general, buprenorphine reduced heart rate but had no significant effect on arterial blood pressure in conscious rats and dogs. 4. In anaesthetized, open-chest cats buprenorphine (0.10 and 1.0 mg/kg, i.v.) caused no major haemodynamic changes. 5. Buprenorphine (0.01-10 mg/kg i.a.) and morphine (0.30-30 mg/kg, i.a.) increased arterial PCO2 values and reduced PO2 values in conscious rats. With doses of buprenorphine greater than 0.10 mg/kg (a) the duration of respiratory depression became less, (b) ceiling effects occurred such that the maximum effects produced were less than those obtained with morphine. 6. Buprenorphine was a potent and long-lasting antagonist of citric acid-induced coughing in guinea-pigs. 7. At a dose level 20 times greater than the ED50 for antinociception (tail pressure), morphine suppressed urine output to a greater extent than the corresponding dose of buprenorphine in rats. 8. Over the range 0.01-1.0 mg/kg (s.c.), buprenorphine slowed the passage of a charcoal meal along the gastrointestinal tract in rats. After doses in excess of 1 mg/kg, the meal travelled increasingly further such that the distances measured at 10 and 30 mg/kg did not differ significantly from control values. In contrast, the morphine dose-response relationship was linear. PMID:409449

  19. Atipamezole reverses ketamine-dexmedetomidine anesthesia without altering the antinociceptive effects of butorphanol and buprenorphine in female C57BL/6J mice.

    PubMed

    Izer, Jenelle M; Whitcomb, Tiffany L; Wilson, Ronald P

    2014-11-01

    Butorphanol and buprenorphine are common analgesics used in laboratory mice. Inadvertent attenuation of the antinociceptive effects of these analgesics via the administration of an anesthetic reversal agent could result in postprocedural pain and distress, with subsequent negative effects on animal welfare, study outcomes, and regulatory compliance. This study was undertaken to determine whether atipamezole reverses ketamine-dexmedetomidine anesthesia and alters the antinociceptive effects of butorphanol and buprenorphine in female C57BL/6J mice. Atipamezole reliably reversed the anesthetic effects of ketamine-dexmedetomidine, and mice were ambulatory 17.4 ± 30.6 min after administration of the α2-adrenoreceptor antagonist. Atipamezole alone had no significant effect on tail-flick latency and did not alter the antinociceptive properties of butorphanol or low-dose (0.05 mg/kg) or high-dose (0.1 mg/kg) buprenorphine in female C57BL/6J mice. After reversal of ketamine-dexmedetomidine anesthesia, tail-flick latency at 30, 60, and 150 min after analgesic treatment differed significantly between mice treated with atipamezole alone and those given atipamezole followed by butorphanol or high-dose buprenorphine. These results suggest that the analgesic effects of butorphanol and buprenorphine are not affected by atipamezole. Buprenorphine (0.1 mg/kg) administered 30 min prior to or at the time of anesthesia resulted in a greater magnitude of antinociception after antagonism of anesthesia than when given at the time of reversal. Given these results, we recommend the use of ketamine-dexmedetomidine anesthesia with buprenorphine administered either preemptively or at the time of anesthetic induction to provide a defined period of surgical anesthesia that is effectively reversed by atipamezole. PMID:25650975

  20. Simultaneous quantification of buprenorphine, naloxone and phase I and II metabolites in plasma and breastmilk by liquid chromatography-tandem mass spectrometry.

    PubMed

    Swortwood, Madeleine J; Scheidweiler, Karl B; Barnes, Allan J; Jansson, Lauren M; Huestis, Marilyn A

    2016-05-13

    Opioid abuse during pregnancy is associated with fetal growth restriction, placental abruption, preterm labor, fetal death, and Neonatal Abstinence Syndrome. Current guidelines for medication-assisted opioid addiction treatment during pregnancy are methadone or buprenorphine monotherapy. Buprenorphine/naloxone combination therapy (Suboxone(®)) has not been thoroughly evaluated during pregnancy and insufficient naloxone safety data exist. While methadone- and buprenorphine-treated mothers are encouraged to breastfeed, no studies to date investigated naloxone concentrations during breastfeeding following Suboxone administration. For this reason, we developed and fully validated a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of buprenorphine, buprenorphine-glucuronide, norbuprenorphine, norbuprenorphine-glucuronide, naloxone, naloxone-glucuronide and naloxone-N-oxide in 100μL human plasma and breastmilk in a single injection following protein precipitation and solid-phase extraction. Lowest limits of quantification were 0.1-2μg/L with 20-100μg/L upper limits of linearity. Bias and imprecision were <±16%. Matrix effects ranged from -57.9 to 11.2 and -84.6 to 29.3% in plasma and breastmilk, respectively. All analytes were stable (within ±20% change from baseline) under all tested conditions (24h room temperature, 72h at 4°C, 3 freeze/thaw cycles at -20°C, and in the autosampler for 72h at 4°C). For proof of concept, buprenorphine and its metabolites were successfully quantified in authentic positive maternal and infant plasma and paired breastmilk specimens. This comprehensive, highly sensitive and specific method detects multiple buprenorphine markers in a small specimen volume. PMID:27083254

  1. Buprenorphine for cancer pain: is it ready for prime time?

    PubMed

    Prommer, Eric

    2015-12-01

    Buprenorphine (BUP) is a semisynthetic derivative of the opium alkaloid thebaine found in the poppy Papaver somniferum. Its chemical structure contains the morphine structure but differs by having a cyclopropylmethyl group. Buprenorphine is a potent µ opioid agonist. Buprenorphine undergoes extensive first-pass metabolism in the liver and gut. The development of a transdermal BUP formulation in 2001 led to its evaluation in cancer pain. This article provides the practitioner with an update on the current role of BUP in cancer care. It highlights data suggesting effectiveness in various types of cancer pain. The article reviews pharmacology, routes of administration, adverse effects, drug interactions, and cost considerations. PMID:25163678

  2. Sleep disordered breathing in patients receiving therapy with buprenorphine/naloxone.

    PubMed

    Farney, Robert J; McDonald, Amanda M; Boyle, Kathleen M; Snow, Gregory L; Nuttall, R T; Coudreaut, Michael F; Wander, Theodore J; Walker, James M

    2013-08-01

    Patients using chronic opioids are at risk for exceptionally complex and potentially lethal disorders of breathing during sleep, including central and obstructive apnoeas, hypopnoeas, ataxic breathing and nonapnoeic hypoxaemia. Buprenorphine, a partial μ-opioid agonist with limited respiratory toxicity, is widely used for the treatment of opioid dependency and chronic nonmalignant pain. However, its potential for causing sleep disordered breathing has not been studied. 70 consecutive patients admitted for therapy with buprenorphine/naloxone were routinely evaluated with sleep medicine consultation and attended polysomnography. The majority of patients were young (mean±sd age 31.8±12.3 years), nonobese (mean±sd body mass index 24.9±5.9 kg·m(-2)) and female (60%). Based upon the apnoea/hypopnoea index (AHI), at least mild sleep disordered breathing (AHI ≥5 events·h(-1)) was present in 63% of the group. Moderate (AHI ≥15- <30 events·h(-1)) and severe (AHI ≥30 events·h(-1)) sleep apnoea was present in 16% and 17%, respectively. Hypoxaemia, defined as an arterial oxygen saturation measured by pulse oximetry, of <90% for ≥10% of sleep time, was present in 27 (38.6%) patients. Despite the putative protective ceiling effect regarding ventilatory suppression observed during wakefulness, buprenorphine may induce significant alterations of breathing during sleep at routine therapeutic doses. PMID:23100497

  3. Oligodendrocyte Responses to Buprenorphine Uncover Novel and Opposing Roles of μ-Opioid- and Nociceptin/Orphanin FQ Receptors in Cell Development: Implications for Drug Addiction Treatment During Pregnancy

    PubMed Central

    Eschenroeder, Andrew C.; Vestal-Laborde, Allison A.; Sanchez, Emilse S.; Robinson, Susan E.; Sato-Bigbee, Carmen

    2011-01-01

    While the classical function of myelin is the facilitation of saltatory conduction, this membrane and the oligodendrocytes, the cells that make myelin in the central nervous system (CNS), are now recognized as important regulators of plasticity and remodeling in the developing brain. As such, oligodendrocyte maturation and myelination are among the most vulnerable processes along CNS development. We have shown previously that rat brain myelination is significantly altered by buprenorphine, an opioid analogue currently used in clinical trials for managing pregnant opioid addicts. Perinatal exposure to low levels of this drug induced accelerated and increased expression of myelin basic proteins (MBPs), cellular and myelin components that are markers of mature oligodendrocytes. In contrast, supra-therapeutic drug doses delayed MBP brain expression and resulted in a decreased number of myelinated axons. We have now found that this biphasic-dose response to buprenorphine can be attributed to the participation of both the μ-opioid receptor (MOR) and the nociceptin/orphanin FQ receptor (NOP receptor) in the oligodendrocytes. This is particularly intriguing because the NOP receptor/nociceptin system has been primarily linked to behavior and pain regulation, but a role in CNS development or myelination has not been described before. Our findings suggest that balance between signaling mediated by (a) MOR activation and (b) a novel, yet unidentified pathway that includes the NOP receptor, plays a crucial role in the timing of oligodendrocyte maturation and myelin synthesis. Moreover, exposure to opioids could disrupt the normal interplay between these two systems altering the developmental pattern of brain myelination. PMID:22002899

  4. Oligodendrocyte responses to buprenorphine uncover novel and opposing roles of μ-opioid- and nociceptin/orphanin FQ receptors in cell development: implications for drug addiction treatment during pregnancy.

    PubMed

    Eschenroeder, Andrew C; Vestal-Laborde, Allison A; Sanchez, Emilse S; Robinson, Susan E; Sato-Bigbee, Carmen

    2012-01-01

    Although the classical function of myelin is the facilitation of saltatory conduction, this membrane and the oligodendrocytes, the cells that make myelin in the central nervous system (CNS), are now recognized as important regulators of plasticity and remodeling in the developing brain. As such, oligodendrocyte maturation and myelination are among the most vulnerable processes along CNS development. We have shown previously that rat brain myelination is significantly altered by buprenorphine, an opioid analogue currently used in clinical trials for managing pregnant opioid addicts. Perinatal exposure to low levels of this drug induced accelerated and increased expression of myelin basic proteins (MBPs), cellular and myelin components that are markers of mature oligodendrocytes. In contrast, supra-therapeutic drug doses delayed MBP brain expression and resulted in a decreased number of myelinated axons. We have now found that this biphasic-dose response to buprenorphine can be attributed to the participation of both the μ-opioid receptor (MOR) and the nociceptin/orphanin FQ receptor (NOP receptor) in the oligodendrocytes. This is particularly intriguing because the NOP receptor/nociceptin system has been primarily linked to behavior and pain regulation, but a role in CNS development or myelination has not been described before. Our findings suggest that balance between signaling mediated by (a) MOR activation and (b) a novel, yet unidentified pathway that includes the NOP receptor, plays a crucial role in the timing of oligodendrocyte maturation and myelin synthesis. Moreover, exposure to opioids could disrupt the normal interplay between these two systems altering the developmental pattern of brain myelination. PMID:22002899

  5. The Effects of Maternally Administered Methadone, Buprenorphine and Naltrexone on Offspring: Review of Human and Animal Data

    PubMed Central

    Farid, W.O; Dunlop, S.A; Tait, R.J; Hulse, G.K

    2008-01-01

    Most women using heroin are of reproductive age with major risks for their infants. We review clinical and experimental data on fetal, neonatal and postnatal complications associated with methadone, the current “gold standard”, and compare these with more recent, but limited, data on developmental effects of buprenorphine, and naltrexone. Methadone is a µ-opioid receptor agonist and is commonly recommended for treatment of opioid dependence during pregnancy. However, it has undesired outcomes including neonatal abstinence syndrome (NAS). Animal studies also indicate detrimental effects on growth, behaviour, neuroanatomy and biochemistry, and increased perinatal mortality. Buprenorphine is a partial µ-opioid receptor agonist and a κ-opioid receptor antagonist. Clinical observations suggest that buprenorphine during pregnancy is similar to methadone on developmental measures but is potentially superior in reducing the incidence and prognosis of NAS. However, small animal studies demonstrate that low doses of buprenorphine during pregnancy and lactation lead to changes in offspring behaviour, neuroanatomy and biochemistry. Naltrexone is a non-selective opioid receptor antagonist. Although data are limited, humans treated with oral or sustained-release implantable naltrexone suggest outcomes potentially superior to those with methadone or buprenorphine. However, animal studies using oral or injectable naltrexone have shown developmental changes following exposure during pregnancy and lactation, raising concerns about its use in humans. Animal studies using chronic exposure, equivalent to clinical depot formulations, are required to evaluate safety. While each treatment is likely to have maternal advantages and disadvantages, studies are urgently required to determine which is optimal for offspring in the short and long term. PMID:19305793

  6. Implementing opioid substitution in Lebanon: Inception and challenges.

    PubMed

    El-Khoury, Joseph; Abbas, Zeinab; Nakhle, Pascale E; Matar, Marie-Therese

    2016-05-01

    Opioid Substitution Treatment (OST) is a firmly established method of treating and managing dependence to opioids in Europe, the US and rest of the developed world. It has a solid evidence base and a positive safety track record. Dissemination of its practice, in parallel to the acceptance of harm reduction as an effective approach, is still timid in low and middle Income countries. After years of advocacy on the parts of clinicians and the voluntary sector, the government of Lebanon launched a national opioid substitution program in 2011 using buprenorphine as the substance of substitution. Lebanon is one of the first countries in the MENA region to establish such a program despite a difficult socio-political context. This paper provides the background of harm reduction efforts in the region and presents the outline of the program from inception to present date. Challenges and recommendations for the future are also discussed. The Lebanese experience with opioid substitution is encouraging so far and can be used as a template for others in the region who might be contemplating broadening the range of services available to tackle addiction to heroin and related substances. PMID:27114000

  7. Transdermal Buprenorphine Patches for Postoperative Pain Control in Abdominal Surgery

    PubMed Central

    Kumar, Santosh; Singh, Prithvi Kumar; Verma, Reetu; Chandra, Girish; Bhatia, Vinod Kumar; Singh, Dinesh; Bogra, Jaishri

    2016-01-01

    Introduction Buprenorphine is a semi-synthetic derivative of thebaine; its low concentration is sufficient to provide effective pain relief. Aim To evaluate the efficacy of transdermal buprenorphine patch in postoperative pain management. Materials and Methods After ethical approval and taking informed consent from the patients, they were randomized into three groups (n=30 in each group) using a computer generated random number table. Group A: placebo patch; Group B: buprenorphine (10mg) patch and Group C: buprenorphine (20mg) patch. Haemodynamic and analgesic effects were compared by using analysis of variance (ANOVA) followed by Turkey’s post hoc test. The proportion of side effects was compared using the Chi-square test. Results Haemodynamic changes were not statistically different in all the three groups A, B and C, whereas at the end of surgery VAS score of Group A subjects was significantly higher (4.93±0.98) as compared to Group B (1.73±0.64) and Group C (1.40±0.50). On 2nd postoperative day, no pain was reported by the Group C patients and on 4th day after surgery, no pain was reported by Group B patients. Conclusion The transdermal buprenorphine patch (20mg) was effective in attenuating postoperative pain, maintaining haemodynamic stability requiring no rescue analgesia, with fewer postoperative rescue analgesic requirements in low dose of buprenorphine patch (10mg) group. PMID:27504383

  8. Uptake and delivery of hepatitis C treatment in opiate substitution treatment: perceptions of clients and health professionals.

    PubMed

    Treloar, C; Newland, J; Rance, J; Hopwood, M

    2010-12-01

    Uptake of treatment for hepatitis C virus (HCV) infection is very low particularly among people who have injected drugs. Opiate substitution treatment (OST) programs, with a high prevalence of people living with HCV, have been a site of growing interest in the delivery of hepatitis C treatment. There has been no exploration of OST clients' and health professionals' perceptions of the barriers and facilitators to uptake and delivery of HCV treatment in OST clinics from personal and organizational perspectives. This qualitative study involved interviews with 27 OST clients in New South Wales and a focus group and interviews with 22 Australian OST health professionals. Clients and health professionals viewed hepatitis C treatment in OST as a 'one-stop-shop' model which could increase access to and uptake of treatment and build on existing relationships of trust between OST client and health professional. Elements of the organizational culture were also noted as barriers to HCV treatment delivery including concerns about confidentiality, lack of discussion of HCV treatment and that HCV treatment was not perceived by clinicians as a legitimate activity of OST clinics. OST client participants also reported a number of personal barriers to engaging with HCV treatment including family responsibilities (and concerns about treatment side effects), unstable housing, comorbidities and perceptions of the unsatisfactory level of treatment efficacy. These findings emphasize the need for future research and delivery of services which addresses the complexity of care and treatment for people in marginalized social circumstances. PMID:20070504

  9. Preparing cationic cotton linter cellulose with high substitution degree by ultrasonic treatment.

    PubMed

    Zhang, Fulong; Pang, Zhiqiang; Dong, Cuihua; Liu, Zong

    2015-11-01

    As an important cellulose derivative, cationic cellulose has becoming an attractive material. However, it remains challenging to produce cationic cellulose with high substitute degree. In this paper, we successfully increased the substitute degree of cationic cellulose by introducing ultrasonic treatment, which efficiently breaks hydrogen bonds of the chemical structure of cationic cellulose. Properties of cationic cellulose were studied by scanning electron spectroscope (SEM), contact angle, X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Experimental results show that the cationic cellulose has rougher surface and lower crystallinity degree as compared to the original sample. TGA analysis verifies that the thermostability of CLC decreases after the cationic modification. The residual of the cationic cellulose (25 wt%) after pyrolysis increases significantly as compared to that of the original cellulose (15 wt%). PMID:26256343

  10. Psychological Barriers to Tobacco Cessation in Indian Buprenorphine-Naloxone Maintained Patients: A Pilot Study

    PubMed Central

    Mandal, Piyali; Jain, Raka; Jhanjee, Sonali; Sreenivas, V.

    2015-01-01

    Context: The prevalence of smoking in opioid agonist treatment programmes remains high, leading to significant tobacco related health hazards and mortality. This is the first study from India addressing tobacco cessation and related barriers among recipients of buprenorphine-naloxone maintenance treatment. Aims: The purpose of the study was to investigate Indian buprenorphine-naloxone maintained patients’ willingness to quit tobacco use, to determine its possible association with demographic, agonist maintenance treatment, tobacco use related variables and personal health and risk perceptions related to health hazards associated with tobacco use. Settings and Design: The study was cross-sectional, observational. It was conducted in the out-patient department of a national level de-addiction centre in India. Materials and Methods: Fifty-five males on buprenorphine-naloxone treatment were assessed using Tobacco Use Characteristics, Fagerstrom Test for Nicotine Dependence (FTND and FTND-ST), Readiness to Change questionnaire (RCQ), Smoker's Perceived Health Risk Evaluation (SPHERE), Importance of Intervention scale and a semi-structured questionnaire. Statistical Analysis: Descriptive statistics, Kruskal-Wallis Chi-square test, Spearman rank order correlation, paired-t test, ANOVA (STATA 9.2 statistical package). Results: Around 65.4% of the subjects were smokers, 9% were using smokeless tobacco only whereas 25.6% were using both. Mean duration of tobacco use was 20 ± 1.5 years. Only 20% had past quit attempts. Only 24% were in action phase of change. Personal health and risk perceptions were poor and only 61.62% considered intervention tobacco smoking cessation important. Conclusions: Higher severity of nicotine dependence, low perception of harm from tobacco warrant immediate attention and need for on-site treatment opportunity. PMID:26664077

  11. Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep.

    PubMed

    Zullian, Chiara; Lema, Pablo; Lavoie, Melissa; Dodelet-Devillers, Aurore; Beaudry, Francis; Vachon, Pascal

    2016-07-01

    The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following blood collections at selected time points, plasma concentrations of buprenorphine was performed by tandem liquid chromatograph-mass spectrometry. Mean buprenorphine concentration was above 0.1 ng/mL at 48 h up to 192 h post-injection for group 1 and it was above 0.1 ng/mL at 48 h up to 72 h post-injection for group 2. In conclusion, a long lasting potential analgesic plasma level of buprenorphine is attained following a single subcutaneous injection of 0.1 mg/kg BW of SR buprenorphine in sheep. However the effective analgesic plasma threshold still needs to be determined in sheep. PMID:27408341

  12. Comparison of the effects of buprenorphine, oxymorphone hydrochloride, and ketoprofen for postoperative analgesia after onychectomy or onychectomy and sterilization in cats.

    PubMed

    Dobbins, Stephanie; Brown, Nancy O; Shofer, Frances S

    2002-01-01

    In this prospective, randomized, blinded study, 68 clinically healthy cats that had onychectomy (n = 20), onychectomy and castration (n = 20), or onychectomy and ovariohysterectomy (n = 28) were randomly assigned to one of four postoperative analgesic treatment groups: buprenorphine (0.01 mg/kg body weight, intramuscularly [IM]), oxymorphone hydrochloride (0.05 mg/kg body weight, IM), ketoprofen (2 mg/kg body weight, IM), and placebo (physiological saline). Sedation scores, visual analog pain scores, cumulative pain scores, serum cortisol concentration, and appetite were used to assess postoperative analgesic effect. Buprenorphine demonstrated the highest efficacy with the lowest cumulative pain scores and serum cortisol levels. PMID:12428880

  13. Effects of HCV Seropositive Status on Buprenorphine Pharmacokinetics in Opioid-Dependent Individuals

    PubMed Central

    Masson, Carmen L.; Rainey, Petrie M.; Moody, David E.; McCance-Katz, Elinore F.

    2013-01-01

    Background and Objectives The purpose of this study was to examine the effect of hepatitis C virus (HCV) infection on buprenorphine pharmacokinetics in opioid-dependent, buprenorphine/naloxone-maintained adults. Methods A retrospective analysis of buprenorphine pharmacokinetics in HCV seropositive and seronegative buprenorphine/naloxone-maintained individuals (N = 49) was undertaken. Results Relative to HCV seronegative subjects, HCV seropositive subjects had higher buprenorphine exposure, as demonstrated by elevated buprenorphine AUC and Cmax values (p = .03 and .02, respectively) and corresponding elevations in the metabolites, buprenorphine-3-glucuronide AUC values (p = .03) and norbuprenorphine-3-glucuronide AUC and C24 values (p = .05 and .03, respectively). Discussion and Conclusions HCV infection was associated with higher plasma concentrations of buprenorphine and buprenorphine metabolites. Scientific Significance and Future Directions Findings suggest the potential for opioid toxicity among HCV-infected patients treated with buprenorphine/naloxone, and possible hepatotoxic effects related to increased buprenorphine exposure. HCV-infected patients receiving buprenorphine may need lower doses to maintain therapeutic plasma concentrations. PMID:24313239

  14. Epidural analgesia with morphine or buprenorphine in ponies with lipopolysaccharide (LPS)-induced carpal synovitis

    PubMed Central

    Freitas, Gabrielle C.; Carregaro, Adriano B.; Gehrcke, Martielo I.; De La Côrte, Flávio D.; Lara, Valéria M.; Pozzobon, Ricardo; Brass, Karin E.

    2011-01-01

    This study evaluated the analgesia effects of the epidural administration of 0.1 mg/kg bodyweight (BW) of morphine or 5 μg/kg BW of buprenorphine in ponies with radiocarpal joint synovitis. Six ponies were submitted to 3 epidural treatments: the control group (C) received 0.15 mL/kg BW of a 0.9% sodium chloride (NaCl) solution; group M was administered 0.1 mg/kg BW of morphine; and group B was administered 5 μg/kg BW of buprenorphine, both diluted in 0.9% NaCl to a total volume of 0.15 mL/kg BW administered epidurally at 10 s/mL. The synovitis model was induced by injecting 0.5 ng of lipopolysaccharide (LPS) in the left or right radiocarpal joint. An epidural catheter was later introduced in the lumbosacral space and advanced up to the thoracolumbar level. The treatment started 6 h after synovitis induction. Lameness, maximum angle of carpal flexion, heart rate, systolic arterial pressure, respiratory rate, temperature, and intestinal motility were evaluated before LPS injection (baseline), 6 h after LPS injection (time 0), and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 h after treatments. Although the model of synovitis produced clear clinical signs of inflammation, the lameness scores in group C were different from the baseline for only up to 12 h. Both morphine and buprenorphine showed a reduction in the degree of lameness starting at 0.5 and 6 h, respectively. Reduced intestinal motility was observed at 0.5 h in group M and at 0.5 to 1 h in group B. Epidural morphine was a more effective analgesic that lasted for more than 12 h and without side effects. It was concluded that morphine would be a valuable analgesic option to alleviate joint pain in the thoracic limbs in ponies. PMID:21731186

  15. Considerations on the role of buprenorphine in recovery from heroin addiction from a UK perspective.

    PubMed

    Nutt, David J

    2015-01-01

    The United Kingdom Drug Strategy emphasises recovery as a key focus in the treatment of drug dependence. A framework for recovery is defined in the Recovery-Orientated Drug Treatment report, written by an expert working group, and comprises four key phases: engagement and stabilisation, including the establishment of treatment goals; preparation for change, involving engagement in psychosocial and pharmacological interventions; active change, including detoxification and medical withdrawal; and completion, including interventions that strengthen community integration. A body of evidence supports the benefits of buprenorphine, a partial agonist at mu opioid receptors, in supporting individualised recovery based on this framework, specifically in relation to the potential for rapid stabilisation, flexibility to transition to other treatment options or achieve abstinence, effective blocking of on-top use of illicit drugs, the treatment of comorbidities through the minimisation of drug-drug interactions, and a good safety profile. In addition, the newer abuse-deterrent formulation of buprenorphine combined with the opioid antagonist naloxone is likely to strengthen recovery-orientated systems of care due to its potential to reduce misuse and diversion. Progress through the recovery journey and the ability to sustain recovery will depend on individual needs and goals and on the amount of recovery capital that individuals have developed. PMID:25389219

  16. Assessment of carprofen and buprenorphine on recovery of mice after surgical removal of the mammary fat pad.

    PubMed

    Adamson, Trinka W; Kendall, Lon V; Goss, Sherri; Grayson, Kevin; Touma, Chadi; Palme, Rupert; Chen, Jane Q; Borowsky, Alexander D

    2010-09-01

    The purpose of this study was to determine the level of pain elicited by mammary fat pad removal surgery and the effects of postoperative analgesics on recovery. Female FVB mice were anesthetized, and mammary fat pad removal was performed. After surgery, mice received carprofen, buprenorphine, a combination of carprofen and buprenorphine, or saline treatment. Additional mice received anesthesia but no surgery or treatment. Food and water intake, body weight, wheel running activity, and a visual assessment score were recorded daily for 4 d after surgery and compared with presurgical findings. Corticosterone metabolites in fecal samples were analyzed at 12 and 24 h postsurgically and compared with baseline values. All surgical groups had significantly decreased food intake at 24 h, with a return to baseline by 48 h. The combination treatment resulted in a significantly decreased water intake and body weight at 24 h. All surgical groups had significantly decreased wheel running activity at 24 h only. The visual assessment scores indicated mild pain for all surgical groups, with the buprenorphine treated mice showing the highest pain index scores, as compared with nonsurgical controls. Fecal corticosterone metabolite levels did not differ significantly between any of the groups or across time. The parameters used in this study did not indicate that administration of these analgesic regimens improved recovery as compared with that of saline-treated mice. Care should be taken when using visual assessment scores to evaluate pain in mice, given that analgesics may have side effects that inadvertently elevate the score. PMID:20858363

  17. Assessment of Carprofen and Buprenorphine on Recovery of Mice after Surgical Removal of the Mammary Fat Pad

    PubMed Central

    Adamson, Trinka W; Kendall, Lon V; Goss, Sherri; Grayson, Kevin; Touma, Chadi; Palme, Rupert; Chen, Jane Q; Borowsky, Alexander D

    2010-01-01

    The purpose of this study was to determine the level of pain elicited by mammary fat pad removal surgery and the effects of postoperative analgesics on recovery. Female FVB mice were anesthetized, and mammary fat pad removal was performed. After surgery, mice received carprofen, buprenorphine, a combination of carprofen and buprenorphine, or saline treatment. Additional mice received anesthesia but no surgery or treatment. Food and water intake, body weight, wheel running activity, and a visual assessment score were recorded daily for 4 d after surgery and compared with presurgical findings. Corticosterone metabolites in fecal samples were analyzed at 12 and 24 h postsurgically and compared with baseline values. All surgical groups had significantly decreased food intake at 24 h, with a return to baseline by 48 h. The combination treatment resulted in a significantly decreased water intake and body weight at 24 h. All surgical groups had significantly decreased wheel running activity at 24 h only. The visual assessment scores indicated mild pain for all surgical groups, with the buprenorphine treated mice showing the highest pain index scores, as compared with nonsurgical controls. Fecal corticosterone metabolite levels did not differ significantly between any of the groups or across time. The parameters used in this study did not indicate that administration of these analgesic regimens improved recovery as compared with that of saline-treated mice. Care should be taken when using visual assessment scores to evaluate pain in mice, given that analgesics may have side effects that inadvertently elevate the score. PMID:20858363

  18. Predictors of dropout from inpatient opioid detoxification with buprenorphine: a chart review.

    PubMed

    Hakansson, Anders; Hallén, Emma

    2014-01-01

    Inpatient withdrawal treatment (detoxification) is common in opioid dependence, although dropout against medical advice often limits its outcome. This study aimed to assess baseline predictors of dropout from inpatient opioid detoxification with buprenorphine, including age, gender, current substance use, and type of postdetoxification planning. A retrospective hospital chart review was carried out for inpatient standard opioid detoxifications using buprenorphine taper, in a detoxification ward in Malmö, Sweden (N = 122). Thirty-four percent of patients (n = 42) dropped out against medical advice. In multivariate logistic regression, dropout was significantly associated with younger age (OR 0.93 [0.89-0.97]) and negatively predicted by inpatient postdetoxification plan (OR 0.41 [0.18-0.94]), thus favouring an inpatient plan as opposed to outpatient treatment while residing at home. Dropout was unrelated to baseline urine toxicology. In opioid detoxification, patients may benefit from a higher degree of postdetoxification planning, including transition to residential treatment, in order to increase the likelihood of a successful detoxification and treatment entry. Young opioid-dependent patients may need particular attention in the planning of detoxification. PMID:25530903

  19. Implementation of a collaborative care management program with buprenorphine in primary care: A comparison between opioid-dependent patients and chronic pain patients using opioids non-medically

    PubMed Central

    Suzuki, Joji; Matthews, Michele L.; Brick, David; Nguyen, Minh-Thuy; Jamison, Robert N.; Ellner, Andrew L.; Tishler, Lori W.; Weiss, Roger D.

    2014-01-01

    Objective To implement a collaborative care management program with buprenorphine in a primary care clinic. Design Prospective observational study. Setting A busy urban academic primary care clinic affiliated with a tertiary care hospital. Participants Opioid dependent patients or chronic pain patients using opioids non-medically were recruited for the study. A total of 45 participants enrolled. Interventions Patients were treated with buprenorphine and managed by a supervising psychiatrist, pharmacist care manager and health coaches. The care manager conducted buprenorphine inductions and all follow-ups visits. Health coaches offered telephonic support. The psychiatrist supervised both the care manager and health coaches. Main outcome measures Primary outcomes were treatment retention at 6 months, and change in the proportion of aberrant toxicology results and opioid craving scores from baseline to 6 months. After data collection, clinical outcomes were compared between opioid dependent patients and chronic pain patients using opioids non-medically. Overall, 55.0% (25/45) of participants remained in treatment at 6 months. PCPs’ attitudes about opioid dependence treatment were surveyed at baseline and at 18-months. Results Forty-three patients (95.6%) accepted treatment and 25 (55.0%) remained in treatment at 6 months. The proportion of aberrant urine toxicology results decreased significantly from baseline to 6 months (p<0.01). Craving scores significantly decreased from baseline to 6 months (p<0.01). Opioid dependent patients, as opposed to chronic pain patients using opioids non-medically, were significantly more likely to complete 6 months of treatment (p<0.05). PCPs’ confidence in treating opioid dependence in primary care increased significantly from baseline to 18-months post-implementation (p<0.01). Conclusion Collaborative care management for opioid dependence with buprenorphine may be feasible in a primary care clinic. More research is needed to

  20. Buprenorphine - the unique opioid adjuvant in regional anesthesia.

    PubMed

    Kosel, Juliusz; Bobik, Piotr; Tomczyk, Michał

    2016-03-01

    Regional anesthesia techniques are commonly used for many surgical procedures alone or as an addition to general anesthesia, because they offer many advantages over general anesthesia. Unfortunately these techniques are partially limited by the time of action of local anesthetics. One of the methods of overcoming this limitation is adding to the local anesthetic solution additional drug - so called adjuvant. Among many adjuvants to local anesthetic drugs tested so far one seems to be particularly interesting - buprenorphine. The aim of this paper is to present pharmacological background for using buprenorphine for regional anesthesia and to review clinical trials of using buprenorphine for all regional anesthesia techniques: spinal and epidural anesthesia, peripheral nerves blocks, local anesthesia and intravenous regional anesthesia. PMID:26758991

  1. The Supply of Physicians Waivered to Prescribe Buprenorphine for Opioid Use Disorders in the United States: A State-Level Analysis

    PubMed Central

    Knudsen, Hannah K.

    2015-01-01

    Objective: The U.S. Food and Drug Administration’s approval of buprenorphine in 2002 expanded options for treating opioid use disorder (OUD). Physicians who intend to treat OUD patients with buprenorphine must seek a waiver to prescribe it, which may contribute to state-by-state variation in the supply of waivered physicians. Method: This study integrates data extracted from the U.S. Drug Enforcement Agency’s database of waivered physicians with state-level indicators of the macro environment, health-related resources, and treatment demand. Results: In December 2013, the average state had 8.0 waivered physicians per 100,000 residents (SD = 5.2). Large regional differences between states in the Northeast relative to states in the Midwest, South, and West were observed. The percentage of residents covered by Medicaid as well as the population-adjusted availability of opioid treatment programs and substance use disorder treatment facilities were positively associated with buprenorphine physician supply. Buprenorphine physician supply was positively correlated with states’ rates of overdose deaths, suggesting that physicians may seek the waiver in response to the magnitude of the opioid problem in their state. Conclusions: States with greater health-related resources, particularly in terms of the supply of opioid treatment programs and substance use disorder treatment programs, had more waivered physicians in 2013. The finding regarding Medicaid coverage suggests that states implementing Medicaid expansion under health reform may experience additional growth in buprenorphine physician supply. However, large regional disparities in the supply of waivered physicians may impede access to care for many Americans with OUD. PMID:26098042

  2. Withdrawal from Buprenorphine/Naloxone and Maintenance with a Natural Dopaminergic Agonist: A Cautionary Note

    PubMed Central

    Blum, Kenneth; Oscar-Berman, Marlene; Femino, John; Waite, Roger L; Benya, Lisa; Giordano, John; Borsten, Joan; Downs, William B; Braverman, Eric R; Loehmann, Raquel; Dushaj, Kristina; Han, David; Simpatico, Thomas; Hauser, Mary; Barh, Debmalya; McLaughlin, Thomas

    2013-01-01

    Background While numerous studies support the efficacy of methadone and buprenorphine for the stabilization and maintenance of opioid dependence, clinically significant opioid withdrawal symptoms occur upon tapering and cessation of dosage. Methods We present a case study of a 35 year old Caucasian female (Krissie) who was prescribed increasing dosages of prescription opioids after carpel tunnel surgery secondary to chronic pain from reflex sympathetic dystrophy and fibromyalgia. Over the next 5 years, daily dosage requirements increased to over 80 mg of Methadone and 300 ug/hr Fentanyl transdermal patches, along with combinations of 12–14 1600 mcg Actig lollipop and oral 100 mg Morphine and 30 mg oxycodone 1–2 tabs q4-6hr PRN for breakthrough pain. Total monthly prescription costs including supplemental benzodiazepines, hypnotics and stimulants exceeded $50,000. The patient was subsequently transferred to Suboxone® in 2008, and the dosage was gradually tapered until her admission for inpatient detoxification with KB220Z a natural dopaminergic agonist. We carefully documented her withdrawal symptoms when she precipitously stopped taking buprenorphine/naloxone and during follow-up while taking KB220Z daily. We also genotyped the patient using a reward gene panel including (9 genes 18 alleles): DRD 2,3,4; MOA-A; COMT; DAT1; 5HTTLLR; OPRM1; and GABRA3. Findings At 432 days post Suboxone® withdrawal the patient is being maintained on KB220Z, has been urine tested and is opioid free. Genotyping data revealed a moderate genetic risk for addiction showing a hypodopaminergic trait. This preliminary case data suggest that the daily use of KB220Z could provide a cost effective alternative substitution adjunctive modality for Suboxone®. We encourage double-blind randomized –placebo controlled studies to test the proposition that KB220Z may act as a putative natural opioid substitution maintenance adjunct. PMID:24273683

  3. Effects of various combinations of benzodiazepines with buprenorphine on arterial blood gases in rats.

    PubMed

    Pirnay, Stéphane O; Mégarbane, Bruno; Borron, Stephen W; Risède, Patricia; Monier, Claire; Ricordel, Ivan; Baud, Frédéric J

    2008-09-01

    Fatalities have been attributed to combinations of high-dose buprenorphine with benzodiazepines. In rats, high-dose buprenorphine combined with midazolam was shown to induce sustained respiratory acidosis, while buprenorphine alone did not. However, the effects of buprenorphine combined with pharmacological doses of benzodiazepines remain unknown. Our objective was to compare the acute effects of four selected benzodiazepines used intravenously at equi-efficacious doses in rats, alone and in combination with buprenorphine on sedation, respiratory rate and arterial blood gases. Buprenorphine (30 mg/kg) did not significantly modify sedation level or respiratory rate, but induced mild and transient effects on pH and PaCO(2) (P < 0.05). Similarly, despite having no effects on respiratory rate, nordiazepam (10 mg/kg), bromazepam (1 mg/kg) and oxazepam (12 mg/kg) mildly and transiently altered pH and PaCO(2) (P < 0.05), whereas clonazepam (5 mg/kg) did not. Buprenorphine combined with each benzodiazepine induced no significant effects on respiratory rate or blood gases, in comparison with buprenorphine alone. However, combinations of oxazepam or nordiazepam with buprenorphine significantly deepened sedation. While both combinations reduced respiratory rate, buprenorphine + 30 mg/kg clonazepam significantly increased PaCO(2) and buprenorphine + 30 mg/kg nordiazepam decreased PaO(2). In conclusion, not all benzodiazepines induce significant respiratory depression at therapeutic doses. We were unable to demonstrate significant effects on rat ventilatory parameters of buprenorphine combined with equi-efficacious pharmacological doses of benzodiazepines in comparison with buprenorphine alone. Our results may suggest that effects of these combinations are rather mild. Respiratory failure may, however, result from the association of buprenorphine with elevated doses of benzodiazepines. PMID:18684226

  4. Cognitive function in short- and long-term substitution treatment: are there differences?

    PubMed

    Soyka, Michael; Zingg, Christina; Koller, Gabriele; Hennig-Fast, Kristina

    2010-03-01

    Cognitive impairment in drug-dependent patients receiving methadone maintenance treatment has been reported previously, although the literature is limited and results remain controversial. Long-term effects under stable methadone maintenance treatment (MMT) and the possibility of improvement in cognitive performance during long-term substitution treatment have rarely been investigated. We performed a comparative study investigating differences in cognitive functions under short- and long-term methadone treatment to test the hypothesis that patients perform better under long- than under short-term MMT. Seventy-seven patients were assessed cross-sectional either at least 30 days after the start of MMT (short-term group, n=35) or after at least 6 months of MMT (long-term group, n=42) with a comprehensive neuropsychological test battery on intelligence, learning and memory, attention and executive functions. Urine screenings were performed immediately before neuropsychological testing to check for concomitant drug use. Our findings may suggest, with all due caution, a slightly better performance of the long-term group in executive functions and visuo-construction. No group differences were found in attentional functions and learning and memory. More longitudinal research and studies controlling for the effects of dosage and duration of opioid addiction are necessary to examine whether cognitive ability may improve under long-term MMT. PMID:19536703

  5. Behavioral drug and HIV risk reduction counseling (BDRC) with abstinence-contingent take-home buprenorphine: a pilot randomized clinical trial.

    PubMed

    Chawarski, M C; Mazlan, M; Schottenfeld, R S

    2008-04-01

    This pilot randomized clinical trial evaluated whether the efficacy of office-based buprenorphine maintenance treatment (BMT), provided with limited counseling or oversight of medication adherence is improved by the addition of individual drug counseling and abstinence-contingent take-home doses of buprenorphine. After a 2-week buprenorphine and stabilization period, heroin dependent individuals (n=24) in Muar, Malaysia were randomly assigned to Standard Services BMT (physician administered advice and support, and weekly, non-contingent medication pick-up) or Enhanced Services (nurse-delivered manual-guided behavioral drug and HIV risk reduction counseling (BDRC) and abstinence-contingent take-home buprenorphine (ACB), 7 day supply maximum). Outcomes included retention, proportion of opioid-negative urine tests, self-reported drug use, and self-reported HIV risk behaviors. 12/12 (100%) of Enhanced Services and 11/12 (92%) of Standard Services participants completed the entire protocol. The proportion of opioid-negative urine tests increased significantly over time for both groups (p<0.001), and the reductions were significantly greater in the Enhanced Services group (p<0.05); Enhanced Services group achieved higher overall proportions of opiate negative urine toxicology tests (87% vs. 69%, p=0.04) and longer periods of consecutive abstinence from opiates (10.3 weeks vs. 7.8 weeks, p=0.154). Both groups significantly reduced HIV risk behaviors during treatment (p<0.05), but the difference between Enhanced and Standard Services (26% vs. 17% reductions from the baseline levels, respectively) was not statistically significant (p=0.9). Manual-guided behavioral drug and HIV risk reduction counseling and abstinence-contingent take-home buprenorphine appear promising for adding to the efficacy of office-based BMT provided with limited drug counseling and medication oversight. PMID:18164145

  6. Office-Based Buprenorphine Versus Clinic-Based Methadone: A Cost-Effectiveness Analysis.

    PubMed

    King, Jordan B; Sainski-Nguyen, Amy M; Bellows, Brandon K

    2016-01-01

    The objective of this analysis was to compare the cost-effectiveness of clinic-based methadone maintenance therapy (MMT) and office-based buprenorphine maintenance therapy (BMT) from the perspective of third-party payers in the United States. The authors used a Markov cost-effectiveness model. A hypothetical cohort of 1000 adult, opioid-dependent patients was modeled over a 1-year time horizon. Patients were allowed to transition between the health states of in opioid dependence treatment and either abusing or not abusing opioids, or to have dropped out of treatment. Probabilities were derived from randomized clinical trials comparing methadone and buprenorphine. Costs included drug and administration, clinic visits, and therapy sessions. Effectiveness outcomes examined were (1) retention in the treatment program and (2) opioid abuse-free weeks. For retention in treatment at 1 year, MMT was more costly ($4,613 vs. $4,155) and more effective (20.3% vs. 15.9%) than BMT, resulting in an incremental cost-effectiveness ratio (ICER) of $10,437 per additional patient retained in treatment. MMT was also more effective than BMT in terms of opioid abuse-free weeks (9.2 vs. 9.1 weeks), resulting in an ICER of $8,515 per opioid abuse-free week gained. One-way sensitivity analyses found costs per week of MMT to have the largest impact on the retention-in-treatment outcome, whereas the probability of dropping out with MMT had the greatest impact on opioid abuse-free weeks. The authors conclude that MMT is cost-effective compared with BMT for the treatment of patients with opioid dependence. However, the treatment of substance abuse is complex, and decision makers should also consider individual patient characteristics when making coverage decisions. PMID:27007583

  7. Morphine, pethidine and buprenorphine disposition in the cat.

    PubMed

    Taylor, P M; Robertson, S A; Dixon, M J; Ruprah, M; Sear, J W; Lascelles, B D; Waters, C; Bloomfield, M

    2001-12-01

    Pharmacokinetics of morphine, buprenorphine and pethidine were determined in 10 cats. Six cats received morphine (0.2 mg/kg) intravenously and four intramuscularly. Five received buprenorphine (0.01 mg/kg) intravenously and six intramuscularly. Six received pethidine (5 mg/kg) intramuscularly. Jugular venous blood samples were collected at time points to 24 h, and plasma morphine concentrations were measured by high performance liquid chromatograpy (HPLC), buprenorphine by radioimmunoassay (RIA) and pethidine by gas chromatography. Our data for morphine show elimination half-life (t1/2el) 76.3 min intravenous (i.v.) and 93.6 min intramuscular (i.m.); mean residence time (MRT) 105.0 and 120.5 min; clearance (Clp) 24.1 and 13.9 mL/kg/min; and volume of distribution (V(dss)) 2.6 and 1.7 L/kg, respectively. Comparable data for buprenorphine are t1/2el 416.8 and 380.2 min; MRT 417.6 and 409.8 min; Clp 16.7 and 23.7 mL/kg/min; and V(dss) 7.1 and 8.9 L/kg. For i.m. pethidine, t1/2el 216.4 min; MRT 307.5 min; Clp 20.8 mL/kg/min and V(dss) 5.2 L/kg. For i.m. dosing, the tmax for morphine, buprenorphine and pethidine were 15, 3 and 10 min, respectively. The pharmacokinetics of the three opioids in cats are broadly comparable with those of the dog, although there is a suggestion that the cat may clear morphine more slowly. PMID:11903869

  8. [Quality of buprenorphine and morphine as components of combined anesthesia].

    PubMed

    Knoche, E; Dick, W; Rummel, C; Konietzke, D

    1988-02-01

    Perioperative effects of buprenorphine during and after combined anesthesia for gynecological laparotomies were compared to those of morphine. In a controlled, randomized study two similar groups of patients received flunitrazepam (0.016 mg/kg) and either buprenorphine (0.008 mg/kg) or morphine (0.333 mg/kg); all patients were ventilated with a N2O/O2-mixture. To maintain adequate anesthesia, additional injections of buprenorphine or morphine and a volatile anesthetic agent (enflurane, less than 1.0 vol.%) were administered as needed. In some patients in both groups the injection of thiopental (1-2 mg/kg) became necessary for induction of anesthesia. Hemodynamic parameters showed a slight but not significant increase during intubation and remained stable intraoperatively (Figs. 1 and 2). The frequencies of additional intraoperative injections of buprenorphine or morphine and modalities of enflurane administration were similar in both groups. Based on an awakeness score, recovery from anesthesia was similar in both groups (Fig. 3). All patients were pain-free for a long period postoperatively (pain score 1-2, duration 6-10 h) (Fig. 4). In both groups respiratory depression could be demonstrated by means of ventilatory CO2 response (Figs. 6 and 7). The respiratory depression was of no clinical importance and seems to have been due to the combination of a long-acting benzodiazepine with an opiate. There were no differences in the occurrence of nausea and vomiting in both groups. Buprenorphine seems to be an alternative to morphine in combined anesthesia. PMID:3284406

  9. Uses of diverted methadone and buprenorphine by opioid-addicted individuals in Baltimore, Maryland

    PubMed Central

    Mitchell, Shannon Gwin; Kelly, Sharon M.; Brown, Barry S.; Reisinger, Heather Schacht; Peterson, James A.; Ruhf, Adrienne; Agar, Michael H.; O'Grady, Kevin E.; Schwartz, Robert P.

    2009-01-01

    This study examined the uses of diverted methadone and buprenorphine among opiate-addicted individuals recruited from new admissions to methadone programs and from out-of-treatment individuals recruited from the streets. Self-report data regarding diversion were obtained from surveys and semi-structured qualitative interviews. Approximately 16% (n=84) of the total sample (N=515) reported using diverted (street) methadone 2–3 times per week for six months or more, and for an average of 7.8 days (SD=10.3) within the past month. The group reporting lifetime use of diverted methadone as compared to the group that did not report such use was less likely to use heroin and cocaine in the 30 days prior to admission (ps < .01) and had lower ASI Drug Composite scores (p < .05). Participants in our qualitative sub-sample (n=22) indicated that street methadone was more widely used than street buprenorphine and that both drugs were largely used as self-medication for detoxification and withdrawal symptoms. Participants reported using low dosages and no injection of either medication was reported. PMID:19874152

  10. Blockade of IL-18 signaling diminished neuropathic pain and enhanced the efficacy of morphine and buprenorphine.

    PubMed

    Pilat, Dominika; Piotrowska, Anna; Rojewska, Ewelina; Jurga, Agnieszka; Ślusarczyk, Joanna; Makuch, Wioletta; Basta-Kaim, Agnieszka; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Currently, the low efficacy of antinociceptive drugs for the treatment of neuropathic pain is a major therapeutic problem. Here, we show the potential role of interleukin (IL)-18 signaling in this phenomenon. IL-18 is an important molecule that performs various crucial functions, including the alteration of nociceptive transmission in response to neuropathic pain. We have studied the changes in the mRNA and protein levels (qRT-PCR and Western blot analysis, respectively) of IL-18, IL-18-binding protein (IL-18BP) and the IL-18 receptor (IL-18R) over time in rats following chronic constriction injury (CCI) of the sciatic nerve. Our study demonstrated that the spinal levels of IL-18BP were slightly downregulated at days 7 and 14 in the rats subjected to CCI. In contrast, the IL-18 and IL-18R mRNA expression and protein levels were elevated in the ipsilateral spinal cord on days 2, 7 and 14. Moreover, in rats exposed to a single intrathecal administration of IL-18BP (50 and 100 ng) 7 or 14 days following CCI, symptoms of neuropathic pain were attenuated, and the analgesia pursuant to morphine and buprenorphine (0.5 and 2.5 μg) was enhanced. In summary, the restoration of the analgesic activity of morphine and buprenorphine via the blockade of IL-18 signaling suggests that increased IL-18 pathway may account for the decreased analgesic efficacy of opioids for neuropathic pain. PMID:26763728

  11. Buprenorphine and major metabolites in blood specimens collected for drug analysis in law enforcement purposes.

    PubMed

    Oechsler, Stephanie; Skopp, Gisela

    2010-02-25

    A liquid chromatographic/electrospray ionization tandem mass spectrometric method for the quantification of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine-3-beta-D-glucuronide (BUPG) and norbuprenorphine-3-beta-D-glucuronide (NBUPG) in serum samples was developed and validated. Pre-treatment of BUP and NBUP was by liquid-liquid extraction, while glucuronides were favourably isolated by solid phase extraction. Separation in 2 separate runs (2 x 5 min) was achieved using isocratic elution. The method was applied to 20 authentic serum specimens collected for law enforcement purposes where BUP intake had been indicated. The parent drug was not detectable in half of the specimens at a lower limit of detection of 0.2 ng/mL, whereas NBUP could be determined from any sample but one. NBUPG is the major metabolite present, which could be identified along with BUPG in all samples under investigation. In authentic specimens it could be advisable to monitor BUP metabolites along with the parent drug. PMID:20006453

  12. Development of an enhanced formulation for delivering sustained release of buprenorphine hydrochloride

    PubMed Central

    Koocheki, S.; Madaeni, S.S.; Niroomandi, P.

    2011-01-01

    To control the minimum effective dose, and reduce the number and quantity of administered potent drugs are unique features of advanced drug delivery in situ forming gel formulation. The efficacy, consistency, and increasing the application of existing injection therapies can be enhanced through optimization of controlled released systems by using FDA approved biodegradable PLGA (poly-d,l-lactide-co-glycolide) polymer. The purpose of this study was to develop different in situ forming implant (ISFI) formulations of buprenorphine hydrochloride for post treatment of drug addicts, acute and chronic pains. The drug releases from different ISFIs membranes with and without Tween 80 were compared over a period of time. Kinetic equation followed the Korsmeyer–Peppas model, as the plots showed high linearity. The influence of this additive on polymer properties was investigated using differential scanning calorimetry (DSC), and the membranes structure was studied by X-ray diffractometry (XRD) and scanning electron microscope (SEM). Data revealed that Tween 80 modified the drug release pattern using diffusion mechanism and decreased the glass transition temperature (Tg) significantly. The degree of crystallinity was decreased after phase inversion which helps the dissolution of drug from membrane. The porosity of modified membranes was in accordance with release profiles. These findings suggest four different in situ forming implant formulations which can release various dose of the buprenorphine hydrochloride in a prolonged time. Also this surfactant can be an attractive additive for modifying the release rate of drugs from PLGA-based membrane drug delivery systems. PMID:23960766

  13. Photocatalytic Properties of Layered Metal Oxides Substituted with Silver by a Molten AgNO3 Treatment.

    PubMed

    Horie, Hirotaka; Iwase, Akihide; Kudo, Akihiko

    2015-07-15

    K4Nb6O17 (BG: 3.67 eV) and Na2W4O13 (BG: 3.12 eV) layered oxide photocatalysts with wide band gaps were treated with a molten AgNO3 to substitute K+ and Na+ with Ag+, resulting in red-shifts of absorption edges in diffuse reflectance spectra. A part of Na+ ions in the interlayer of Na2W4O13 was substituted with Ag+ ions by the molten AgNO3 treatment with keeping the layered structure. Both Ag(I)-substituted K4Nb6O17 and Na2W4O13 showed photocatalytic activities for O2 evolution from aqueous solutions containing a sacrificial reagent utilizing the absorption bands newly formed by the Ag(I)-substitution. Notably, the Ag(I)-substituted Na2W4O13 produced O2 under visible light irradiation. When ball-milled Na2W4O13 was treated with a molten AgNO3, the Ag(I)-substitution rate increased. The Ag(I)-substituted Na2W4O13 with ball-milling showed higher photocatalytic activity for O2 evolution than that without ball-milling. Z-schematic water splitting proceeded under visible light irradiation by combining the Ag(I)-substituted Na2W4O13 of an O2-evolving photocatalyst with Ru-loaded SrTiO3 doped with Rh of a H2-evolving photocatalyst. PMID:26099451

  14. Cannabis as an adjunct to or substitute for opiates in the treatment of chronic pain.

    PubMed

    Lucas, Philippe

    2012-01-01

    There is a growing body of evidence to support the use of medical cannabis as an adjunct to or substitute for prescription opiates in the treatment of chronic pain. When used in conjunction with opiates, cannabinoids lead to a greater cumulative relief of pain, resulting in a reduction in the use of opiates (and associated side-effects) by patients in a clinical setting. Additionally, cannabinoids can prevent the development of tolerance to and withdrawal from opiates, and can even rekindle opiate analgesia after a prior dosage has become ineffective. Novel research suggests that cannabis may be useful in the treatment of problematic substance use. These findings suggest that increasing safe access to medical cannabis may reduce the personal and social harms associated with addiction, particularly in relation to the growing problematic use of pharmaceutical opiates. Despite a lack of regulatory oversight by federal governments in North America, community-based medical cannabis dispensaries have proven successful at supplying patients with a safe source of cannabis within an environment conducive to healing, and may be reducing the problematic use of pharmaceutical opiates and other potentially harmful substances in their communities. PMID:22880540

  15. Efficacy of Buprenorphine/Naloxone Rapidly Dissolving Sublingual Tablets (BNX-RDT) After Switching From BNX Sublingual Film

    PubMed Central

    Gunderson, Erik W.; Sumner, Michael

    2016-01-01

    Objectives: The aim of the study was to evaluate treatment retention, efficacy, and preference ratings among opioid-dependent patients transitioning between a buprenorphine/naloxone rapidly dissolving sublingual tablet formulation (BNX-RDT) and BNX film. Methods: After a 2-day, blinded, fixed-dose induction with BNX-RDT (5.7/1.4 mg and 5.7/1.4 or 11.4/2.8 mg, respectively) or buprenorphine (8 mg and 8 or 16 mg, respectively), patients received open-label titrated doses of BNX-RDT or BNX film (generic buprenorphine induction group) during days 3 to 14. On day 15, patients switched treatment (using a conversion ratio of 5.7–8 mg) and continued switched treatment through day 22. Assessments included treatment retention, opioid withdrawal (Clinical and Subjective Opiate Withdrawal scales), opioid cravings (0–100 visual analog scale [VAS]), and preference ratings. Results: Of the 287 patients who switched from BNX-RDT to BNX film and 279 patients who switched from BNX film to BNX-RDT at day 15, 8.7% and 6.1% withdrew, respectively. Reductions in opioid withdrawal and cravings were similar with both formulations through day 15; after switching treatment, reductions were maintained through day 22 in both groups. Preference ratings at day 22 (patients had received both formulations) favored BNX-RDT for taste, mouthfeel, ease of administration, and overall preference (all P < 0.0001). Conclusions: In both patient groups who switched treatment at day 15, more than 90% were retained in treatment, and reductions in opioid withdrawal and cravings were sustained. A significant majority of patients preferred BNX-RDT over BNX film, the clinical impact of which requires further study. PMID:26918662

  16. Effect of steady-state faldaprevir on the pharmacokinetics of steady-state methadone and buprenorphine-naloxone in subjects receiving stable addiction management therapy.

    PubMed

    Joseph, David; Schobelock, Michael J; Riesenberg, Robert R; Vince, Bradley D; Webster, Lynn R; Adeniji, Abidemi; Elgadi, Mabrouk; Huang, Fenglei

    2015-01-01

    The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC(0-24,ss)), the steady-state maximum concentration of the drug in plasma (C(max,ss)), and the steady-state concentration of the drug in plasma at 24 h (C(24,ss)) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This

  17. Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy

    PubMed Central

    Joseph, David; Schobelock, Michael J.; Riesenberg, Robert R.; Vince, Bradley D.; Webster, Lynn R.; Adeniji, Abidemi; Elgadi, Mabrouk

    2014-01-01

    The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC0–24,ss), the steady-state maximum concentration of the drug in plasma (Cmax,ss), and the steady-state concentration of the drug in plasma at 24 h (C24,ss) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study

  18. Pharmacokinetics of buprenorphine hydrochloride following intramuscular and intravenous administration to American kestrels (Falco sparverius)

    USGS Publications Warehouse

    Gustavsen, Kate A.; Guzman, David Sanchez-Migallon; Knych, Heather K.; Petritz, Olivia A.; Olsen, Glenn H.; Paul-Murphy, Joanne R.

    2014-01-01

    Conclusions and Clinical Relevance—Buprenorphine was rapidly absorbed, and bioavailability was good after IM administration to American kestrels. Plasma buprenorphine concentrations were > 1 ng/mL for 9 hours after both IM and IV administration. These results, in combination with those of a pharmacodynamic study, suggested that the analgesic effects of buprenorphine could last at least 6 to 9 hours in this species. Further investigations of the duration of analgesic effects, multiple-dose protocols, and potential adverse effects of buprenorphine are warranted in American kestrels and other raptors.

  19. Buprenorphine from detox and beyond: preliminary evaluation of a pilot program to increase heroin dependent individuals' engagement in a full continuum of care.

    PubMed

    Donovan, Dennis M; Knox, Patricia C; Skytta, Jenny A F; Blayney, Jessica A; DiCenzo, Jessica

    2013-04-01

    Absence of successful transition to post-detoxification treatment leads to high rates of relapse among detoxified heroin users. The present study evaluated a pilot buprenorphine treatment program (BTP). Heroin dependent individuals were inducted onto buprenorphine/naloxone in detox, maintained while transitioning through an intensive inpatient program (IIP), and gradually tapered off medication over 5 months of outpatient (OP) treatment. Compared to programmatic indicators of treatment engagement in the year prior to BTP implementation, referrals from detox to IIP, entry into and completion of IIP and subsequent OP, and days in OP treatment increased substantially. BTP completers, compared to non-completers, viewed abstinence as more difficult and as requiring more assistance to achieve, were less likely to be current cocaine and alcohol users or to have relapsed during the course of treatment. Although preliminary and in need of replication, initial adjunctive use of buprenorphine in an abstinence-based continuum of care may improve post-detoxification treatment entry, engagement, and completion. PMID:23007109

  20. The causal effect of opioid substitution treatment on HAART medication refill adherence

    PubMed Central

    Nosyk, Bohdan; Min, Jeong E.; Colley, Guillaume; Lima, Viviane D.; Yip, Benita; Milloy, M.-J.S.; Wood, Evan; Montaner, Julio S.G.

    2015-01-01

    Background People who inject drugs (PWID) account for roughly 13% of the prevalent HIV/AIDS population outside of sub-Saharan Africa, and access to opioid substitution treatment (OST) is limited in many settings globally. OST likely facilitates access to HAART, yet sparse evidence is available to support this hypothesis. Our objective was to determine the causal impact of OST exposure on HAART adherence among HIV-positive PWID in a Canadian setting. Methods We executed a retrospective cohort study using linked population-level data for British Columbia, Canada (January 1996–March 2010). We considered HIV-positive PWID after meeting HAART initiation criteria. A marginal structural model was estimated on a monthly timescale using inverse probability of treatment weights. The primary outcome was 95% HAART adherence, according to pharmacy refill compliance. Exposure to OST was defined as 95% of OST receipt, and we controlled for a range of fixed and time-varying covariates. Results Our study included 1852 (63.3%) HIV-positive PWID with a median follow-up of 5.5 years; 34% were female and 39% had previously accessed OST. The baseline covariate-adjusted odds of HAART adherence following OST exposure was 1.96 (95% confidence interval: 1.72–2.24), although the adjusted odds estimated within the marginal structural model was 1.68 (1.48–1.92). Findings were robust to sensitivity analyses on model specification. Conclusion In a setting characterized by universal healthcare and widespread access to both office-based OST and HAART, OST substantially increased the odds of HAART adherence. This underlines the need to address barriers to OST globally to reduce the disease burden of both opioid dependence and HIV/AIDS. PMID:25915170

  1. LC-MS-MS analysis of buprenorphine and norbuprenorphine in whole blood from suspected drug users.

    PubMed

    Seldén, Tor; Roman, Markus; Druid, Henrik; Kronstrand, Robert

    2011-06-15

    A liquid chromatography tandem mass spectrometry method is described for the analysis of buprenorphine and norbuprenorphine in whole blood. Linearity was achieved between 0.2-5 ng/g for buprenorphine and 0.5-5 ng/g for norbuprenorphine. Stability studies on spiked whole blood and an authentic sample showed no degradation of buprenorphine- and norbuprenorphine-glucuronide to their respective aglycones. Buprenorphine and norbuprenorphine showed some degradation when stored at 4°C for three weeks, but was stable when stored at -20°C for 4 weeks. The method was applied to forensic cases of driving under the influence of drugs (DUID) and petty drug offences (PDO) during 2007-2009. Out of 2459 cases analyzed, 322 were positive for both buprenorphine and norbuprenorphine (13%), 219 for buprenorphine only (9%), and 12 for norbuprenorphine only (0.5%). The mean and median concentrations (N=322) were 1.7 and 1.0 ng/g, respectively, for buprenorphine and norbuprenorphine. The mean and median norbuprenorphine/buprenorphine ratios were 1.5 and 1.1, respectively. There was no significant difference in concentration ratios for DUID and PDO cases (p>0.05). We conclude that the described method for analysis of buprenorphine and norbuprenorphine in whole blood could be used to investigate use or misuse of buprenorphine but that many of the cases presented with very low concentrations of buprenorphine. We also conclude that analysis should be performed within two weeks unless samples are stored frozen prior to analysis. PMID:21306845

  2. Effects of d-amphetamine and buprenorphine combinations on speedball (cocaine+heroin) self-administration by rhesus monkeys.

    PubMed

    Mello, Nancy K; Negus, S Stevens

    2007-09-01

    The simultaneous i.v. administration of heroin and cocaine, called a 'speedball,' is often reported clinically, and identification of effective pharmacotherapies is a continuing challenge. We hypothesized that treatment with combinations of a monoamine releaser d-amphetamine, and a mu partial agonist, buprenorphine, might reduce speedball self-administration by rhesus monkeys. Speedballs (0.01 mg/kg/inj cocaine+0.0032 mg/kg/inj heroin) and food (1 g banana-flavored pellets) were available during four daily sessions on a second-order schedule of reinforcement (fixed ratio (FR)2 (variable ratio (VR)16:S)). Monkeys were treated for 10 days with saline or ascending doses of d-amphetamine (0.0032-0.032 mg/kg/h)+buprenorphine (0.075 or 0.237 mg/kg/day) in combination. d-Amphetamine+both doses of buprenorphine produced an amphetamine dose-dependent decrease in speedball self-administration in comparison to the saline treatment baseline (P<0.01-0.001), but food-maintained responding did not change significantly. d-Amphetamine alone (0.032 mg/kg/h) significantly decreased both food (P<0.01) and speedball-maintained responding (P<0.05). During saline control treatment, speedball unit doses of 0.0032 mg/kg/inj cocaine+0.001 mg/kg/inj heroin were at the peak of the speedball dose-effect curve. Daily treatment with 0.01 mg/kg/h d-amphetamine+0.237 mg/kg/day buprenorphine produced a significant downward and rightward shift in the speedball dose-effect curve (P<0.01) and no significant effect on food-maintained responding. A significant decrease in speedball self-administration was sustained over 10 days of treatment. These findings are consistent with our previous reports and suggest that medication mixtures designed to target both the stimulant and the opioid component of the speedball may be an effective approach to polydrug abuse treatment. PMID:17228335

  3. [High-dose buprenorphine for outpatient palliative pain therapy].

    PubMed

    Gastmeier, K; Freye, E

    2009-04-01

    The case of a 78-year-old patient with cancer-related pain and additionally mixed-pain syndrome is presented. Pain therapy with buprenorphine TTS 210 microg/h every 3 days was sufficient in the beginning, later the therapy was changed because of increasing problems of tape fixing during fever periods under chemotherapy to a continuous infusion of buprenorphine intravenously via an external medication pump. During the course of therapy it became necessary to increase the dose to 99.9 mg/day buprenorphine. Under this medication a sufficient pain reduction (median NRS 2-3) over a period of 135 days could be achieved. At the same time the patient was vigilant and cooperative without signs of intoxication until the end of life at home in the presence of his family.If no signs of intoxication occur under extreme opioid therapy and a sufficient pain therapy can be achieved, a rotation to another opioid is not necessary. However, outpatient palliative care requires a frequent adaptation to the individually varying opioid demand of the patient and time-consuming nursing care. PMID:19066981

  4. Evaluation of a Combined Online and in Person Training in the Use of Buprenorphine

    ERIC Educational Resources Information Center

    Gunderson, Erik W.; Levin, Frances R.; Kleber, Herbert D.; Fiellin, David A.; Sullivan, Lynn E.

    2006-01-01

    To evaluate buprenorphine training methodology, we surveyed physicians who had completed a combined online and in person buprenorphine curriculum. Of 53/70 (76%) survey respondents, 57% were psychiatrists and 40% generalists. On a scale of 1 (very poor) to 7 (superlative), the overall training rated a mean of 5.8. The online course (5.0) rated…

  5. Energy Dependence of Measured CT Numbers on Substituted Materials Used for CT Number Calibration of Radiotherapy Treatment Planning Systems

    PubMed Central

    Mahmoudi, Reza; Jabbari, Nasrollah; aghdasi, Mehdi; Khalkhali, Hamid Reza

    2016-01-01

    Introduction For accurate dose calculations, it is necessary to provide a correct relationship between the CT numbers and electron density in radiotherapy treatment planning systems (TPSs). The purpose of this study was to investigate the energy dependence of measured CT numbers on substituted materials used for CT number calibration of radiotherapy TPSs and the resulting errors in the treatment planning calculation doses. Materials and Methods In this study, we designed a cylindrical water phantom with different materials used as tissue equivalent materials for the simulation of tissues and obtaining the related CT numbers. For evaluating the effect of CT number variations of substituted materials due to energy changing of scanner (kVp) on the dose calculation of TPS, the slices of the scanned phantom at three kVp's were imported into the desired TPSs (MIRS and CorePLAN). Dose calculations were performed on two TPSs. Results The mean absolute percentage differences between the CT numbers of CT scanner and two treatment planning systems for all the samples were 3.22%±2.57% for CorePLAN and 2.88%±2.11% for MIRS. It was also found that the maximum absolute percentage difference between all of the calculated doses from each photon beam of linac (6 and 15 MV) at three kVp's was less than 1.2%. Discussion The present study revealed that, for the materials with effective low atomic number, the mean CT number increased with increasing energy, which was opposite for the materials with an effective high atomic number. We concluded that the tissue substitute materials had a different behavior in the energy ranges from 80 to 130 kVp. So, it is necessary to consider the energy dependence of the substitute materials used for the measurement or calibration of CT number for radiotherapy treatment planning systems. PMID:27391672

  6. Development, Implementation, and Evaluation of a Pilot Parenting Educational Intervention in a Pregnancy Buprenorphine Clinic.

    PubMed

    Giles, Averie C; Ren, Dianxu; Founds, Sandra

    2016-01-01

    We developed a pilot evidence-based prenatal educational intervention to increase knowledge of neonatal abstinence syndrome (NAS) and early parenting skills for women with opiate dependency who enrolled in a pregnancy buprenorphine clinic. We developed, implemented, and tested modules regarding expectations during newborn hospitalization for observation or treatment of NAS and regarding evidence-based parenting skills in response to NAS behaviors. Testing evaluated baseline knowledge of early parenting skills with newborns at risk for NAS and change from baseline after the educational intervention. No statistically significant difference in composite knowledge scores was observed. A brief survey completed by the participants postpartum affirmed the perception of women that the educational intervention effectively prepared them for the early postpartum period while their newborns were hospitalized. PMID:27287352

  7. A Question About the Safety of Buprenorphine/Naloxone and Benzodiazepine Drugs.

    PubMed

    Howland, Robert H

    2015-12-01

    Drug overdose is the leading cause of injury death in the United States, and most deaths are related to prescription drugs. A substantial proportion of these deaths involve opioid or benzodiazepine drugs, and many overdoses include a combination of both drug classes. Buprenorphine/naloxone has an unusual pharmacology that distinguishes it from other opioid drugs. Animal and human studies have found that buprenorphine is associated with a ceiling to its cardio-respiratory depressant effect at higher doses, such that it may have a wider safety margin compared to other opioid drugs. Compared to buprenorphine alone, buprenorphine/naloxone is associated with less cardiorespiratory depression. Drug safety data from the National Poison Data System, Drug Abuse Warning Network, and other sources suggest that the safety of buprenorphine/naloxone is favorable compared to the morbidity and mortality associated with other opioid drugs and other classes of psychotropic drugs. PMID:26653090

  8. Schedules of controlled substances: rescheduling of buprenorphine from schedule V to schedule III. Final rule.

    PubMed

    2002-10-01

    This final rule is issued by the Deputy Administrator of the Drug Enforcement Administration (DEA) to reschedule buprenorphine from a Schedule V narcotic to a Schedule III narcotic under the Controlled Substances Act (CSA). This action is based on a rescheduling recommendation by the Department of Health and Human Services (DHHS) and a DEA review indicating that buprenorphine meets the criteria of a Schedule III narcotic. The DEA published a proposed rule to reschedule buprenorphine on March 21, 2002 (67 FR 13114). The comment period was extended for an additional 30 days until May 22, 2002 (67 FR 20072). The DEA received ten comments but no requests for hearings. This final action will impose the regulatory controls and criminal sanctions of a Schedule III narcotic on those persons who handle buprenorphine or products containing buprenorphine PMID:12369590

  9. Using a dermal skin substitute in the treatment of chronic wounds secondary to recessive dystrophic epidermolysis bullosa: a case series.

    PubMed

    Sibbald, R Gary; Zuker, Ron; Coutts, Patricia; Coelho, Sunita; Williamson, Diane; Queen, Douglas

    2005-11-01

    Epidermolysis bullosa is a family of genetic disorders that cause blistering and shearing of the skin from even the mildest trauma. Care generally focuses on preventing infection, protecting the skin against trauma, attending to nutritional deficiencies and dietary complications, minimizing deformities and contractures, and providing psychological support for the entire family. One approach to the treatment of chronic wounds in Epidermolysis bullosa involves tissue engineering, where cells similar to those of the skin, grown on a three-dimensional scaffold, are used to induce healing. Charts of six young people (ages 8 years to 23 years; four girls, two boys) with recessive dystrophic Epidermolysis bullosa who received applications of a dermal skin substitute to persistent erosions at multiple body sites (55) at successive clinic visits were reviewed. Each patient received between seven and 32 skin substitute applications to between six and 19 sites; patients were followed for at least 8 weeks. At weeks 1 to 2, epidermal coverage ranged between 80% and 100%. Some sites had persistent coverage but others experienced breakdown. Four patients had hand surgery and the living skin substitute was used postsurgically to provide coverage for the epidermal defects. Overall in these six cases, the dermal skin substitute proved advantageous to wound protection, healing, and symptom relief. Compassionate care combined with optimal wound care and advancing technology may offer an effective antidote to the wounding and pain of this devastating disease. PMID:16319445

  10. Trends of People Using Drugs and Opioid Substitute Treatment Recorded in England and Wales General Practice (1994-2012)

    PubMed Central

    Davies, Hilary R.; Nazareth, Irwin; Petersen, Irene

    2015-01-01

    Background Illicit drug use is a multifaceted public-health problem with potentially serious impacts. The United Kingdom has one of the highest prevalence of illegal drug use in Europe. Reduction of overall illegal drug use in England and Wales has decreased from 11% to 8.2% (2012/13) over the past 10 years. People who use drugs often seek help from their family doctors. Aims To investigate General Practitioners (family doctors) first recording of drug use and opioid substitute treatment in primary care settings. Design A descriptive study design. Males and females (16-64 years old) were extracted from The Health Improvement Network (THIN) database. Setting England and Wales primary care. Method The first recording of drug use and opioid substitution treatment in primary care was estimated for the period (1994-2012). Poisson regressions were conducted to estimate incidence risk ratios (IRR). Results We identified 33,508 first recordings of drug use and 10,869 individuals with prescriptions for opioid substitute treatment. Overall, males (IRR 2.02, 95% CI:1.97–2.07), people in the age-group; 16-24 (IRR 6.7, 95% CI:6.4–6.9) compared to those over 25 years and the most deprived (IRR 4.2, 95% CI:3.9–4.4) were more likely to have a recording of drug use. Males (IRR 1.2 95% CI:1.2–1.3), in the age-group; 25-34 (IRR 1.8 95% CI:1.7–1.9) and the most deprived (IRR 3.9 95% CI:3.6–4.3) were the groups more likely to have a opioid substitute treatment prescription. Conclusion It is evident from this study that there is little recording of drug use and opioid substitute treatment in primary care. Most drug users do not receive treatment in primary care. PMID:25923806

  11. A pilot survey of attitudes and knowledge about opioid substitution therapy for HIV-infected prisoners.

    PubMed

    Springer, Sandra A; Bruce, Robert D

    2008-01-01

    A majority of inmates in the state of Connecticut Department of Corrections use opioids or are opioid dependent before incarceration. None of the state's prisons offer opioid substitution therapy other than for detoxification or maintenance therapy for women during pregnancy. On release to the community, most prisoners relapse to drug use and this has been associated with higher recidivism rates, and less adherence to antiretroviral medications for HIV-infected persons. Nationally and internationally, methadone (METH) and buprenorphine (BUP) have been found to decrease relapse to drug use, decrease recidivism rates, improve adherence to antiretroviral medications, decrease HIV-risk taking behaviors, and improve mortality. However, the general knowledge about opioid substitution therapy among correctionalfacility staff has been reported as substandard. This pilot study compiled results of answers to anonymous surveys from 27 individuals who work directly with inmates in a patient-care capacity for the Connecticut Department of Corrections (CT DOC) and CT DOC case-management referral program (Project TLC) in the year 2006. The surveys included questions regarding current attitudes and knowledge about opioid substitution therapy for prisoners. A minority of respondents refer released prisoners with a history of opioid dependency to METH or BUP treatment. The majority of correctional workers and case-management referral workers did not have knowledge about BUP or METH's ability to improve health and decrease HIV risk taking behaviors. This study found that more education of individuals treating and caring for HIV-infected opioid dependent prisoners is needed. PMID:18557164

  12. Mediation of buprenorphine analgesia by a combination of traditional and truncated mu opioid receptor splice variants.

    PubMed

    Grinnell, Steven G; Ansonoff, Michael; Marrone, Gina F; Lu, Zhigang; Narayan, Ankita; Xu, Jin; Rossi, Grace; Majumdar, Susruta; Pan, Ying-Xian; Bassoni, Daniel L; Pintar, John; Pasternak, Gavril W

    2016-10-01

    Buprenorphine has long been classified as a mu analgesic, although its high affinity for other opioid receptor classes and the orphanin FQ/nociceptin ORL1 receptor may contribute to its other actions. The current studies confirmed a mu mechanism for buprenorphine analgesia, implicating several subsets of mu receptor splice variants. Buprenorphine analgesia depended on the expression of both exon 1-associated traditional full length 7 transmembrane (7TM) and exon 11-associated truncated 6 transmembrane (6TM) MOR-1 variants. In genetic models, disruption of delta, kappa1 or ORL1 receptors had no impact on buprenorphine analgesia, while loss of the traditional 7TM MOR-1 variants in an exon 1 knockout (KO) mouse markedly lowered buprenorphine analgesia. Loss of the truncated 6TM variants in an exon 11 KO mouse totally eliminated buprenorphine analgesia. In distinction to analgesia, the inhibition of gastrointestinal transit and stimulation of locomotor activity were independent of truncated 6TM variants. Restoring expression of a 6TM variant with a lentivirus rescued buprenorphine analgesia in an exon 11 KO mouse that still expressed the 7TM variants. Despite a potent and robust stimulation of (35) S-GTPγS binding in MOR-1 expressing CHO cells, buprenorphine failed to recruit β-arrestin-2 binding at doses as high as 10 µM. Buprenorphine was an antagonist in DOR-1 expressing cells and an inverse agonist in KOR-1 cells. Buprenorphine analgesia is complex and requires multiple mu receptor splice variant classes but other actions may involve alternative receptors. PMID:27223691

  13. Long-term administration of high doses of transdermal buprenorphine in cancer patients with severe neuropathic pain

    PubMed Central

    Leppert, Wojciech; Kowalski, Grzegorz

    2015-01-01

    Background Buprenorphine is often administered by the transdermal route (transdermal buprenorphine [TB]) in cancer patients with severe neuropathic pain. However, high doses of TB of 140 µg/h are rarely used. Patients and methods Three cancer patients with severe neuropathic Numeric Rating Scale (NRS) pain scores of 8–10 who were successfully treated with high doses of TB up to 140 µg/h along with other opioids and adjuvant analgesics. Results TB was administered for a long period of follow-up (9 months to 4 years, including 34–261 days of treatment with the dose of 140 µg/h), which allowed achievement of satisfactory analgesia (NRS 3–5) and good treatment tolerance. In all three patients, TB dose was gradually titrated from 35 to 140 µg/h, and all patients used morphine at least for some time for breakthrough and background pain management along with adjuvant analgesics. Two patients continued the treatment with TB until the end of life, and one patient is still receiving the treatment. Conclusion TB at doses of up to 140 µg/h in cancer patients with severe neuropathic pain seems to be effective and safe in combination with other opioids and with adjuvant analgesics, and may significantly improve patients’ quality of life. Clinical studies may explore higher than maximal 140 µg/h TB doses recommended by a manufacturer, and also in combination with other opioids and adjuvant analgesics. PMID:26675083

  14. Umbilical cord monitoring of in utero drug exposure to buprenorphine and correlation with maternal dose and neonatal outcomes.

    PubMed

    Concheiro, Marta; Jones, Hendreé E; Johnson, Rolley E; Choo, Robin; Shakleya, Diaa M; Huestis, Marilyn A

    2010-10-01

    Buprenorphine is under investigation in the U.S. as pharmacotherapy for opioid-dependent pregnant women. Buprenorphine and metabolites were quantified in umbilical cord specimens from women receiving daily buprenorphine doses. Correlations between maternal buprenorphine dose, buprenorphine and metabolite umbilical cord concentrations, and neonatal outcomes were investigated, as well as the ability to identify heroin and cocaine relapse during pregnancy. Umbilical cord concentrations were compared to those of matched umbilical cord plasma and meconium. Buprenorphine metabolites were detected in all cords, but buprenorphine itself was absent. Concentration ranges were 1.2-5.1 ng/g norbuprenorphine, 1.7-4.2 ng/g buprenorphine-glucuronide, and 8.3-23 ng/g norbuprenorphine-glucuronide. Cord concentrations were similar to those in plasma, and lower (16-210-fold), although statistically correlated, than those in meconium. Significant positive correlations were observed for buprenorphine-glucuronide concentrations in umbilical cord and mean maternal BUP daily dose throughout pregnancy and third trimester, but buprenorphine biomarker concentrations did not predict neonatal outcomes. Opiate concentrations were lower (200-fold) in umbilical cord than in meconium, and when cocaine was present in meconium, it was not identified in cord. Umbilical cord can serve as an alternative matrix for identifying prenatal drug-exposure, but is much less sensitive than meconium. Buprenorphine provided a controlled drug administration model for evaluating drug disposition in the maternal-fetal dyad. PMID:21819795

  15. Pharmacokinetic interactions between buprenorphine/naloxone and tipranavir/ritonavir in HIV-negative subjects chronically receiving buprenorphine/naloxone.

    PubMed

    Bruce, R Douglas; Altice, Frederick L; Moody, David E; Lin, Shen-Nan; Fang, Wenfang B; Sabo, John P; Wruck, Jan M; Piliero, Peter J; Conner, Carolyn; Andrews, Laurie; Friedland, Gerald H

    2009-12-01

    HIV-infected patients with opioid dependence often require opioid replacement therapy. Pharmacokinetic interactions between HIV therapy and opioid dependence treatment medications can occur. HIV-seronegative subjects stabilized on at least 3 weeks of buprenorphine/naloxone (BUP/NLX) therapy sequentially underwent baseline and steady-state pharmacokinetic evaluation of open-label, twice daily tipranavir 500 mg co-administered with ritonavir 200 mg (TPV/r). Twelve subjects were enrolled and 10 completed the study. Prior to starting TPV/r, the geometric mean BUP AUC(0-24h) and C(max) were 43.9 ng h/mL and 5.61 ng/mL, respectively. After achieving steady-state with TPV/r (> or = 7 days), these values were similar at 43.7 ng h/mL and 4.84 ng/mL, respectively. Similar analyses for norBUP, the primary metabolite of BUP, demonstrated a reduction in geometric mean for AUC(0-24h) [68.7-14.7 ng h/mL; ratio=0.21 (90% CI 0.19-0.25)] and C(max) [4.75-0.94 ng/mL; ratio=0.20 (90% CI 0.17-0.23)]. The last measurable NLX concentration (C(last)) in the concentration-time profile, never measured in previous BUP/NLX interaction studies with antiretroviral medications, was decreased by 20%. Despite these pharmacokinetic effects on BUP metabolites and NLX, no clinical opioid withdrawal symptoms were noted. TPV steady-state AUC(0-12h) and C(max) decreased 19% and 25%, respectively, and C(min) was relatively unchanged when compared to historical control subjects receiving TPV/r alone. No dosage modification of BUP/NLX is required when co-administered with TPV/r. Though mechanistically unclear, it is likely that decreased plasma RTV levels while on BUP/NLX contributed substantially to the decrease in TPV levels. BUP/NLX and TPV/r should therefore be used cautiously to avoid decreased efficacy of TPV in patients taking these agents concomitantly. PMID:19726139

  16. Treating Homeless Opioid Dependent Patients with Buprenorphine in an Office-Based Setting

    PubMed Central

    LaBelle, Colleen T.; Richardson, Jessica M.; O’Connell, James J.; Hohl, Carole A.; Cheng, Debbie M.; Samet, Jeffrey H.

    2007-01-01

    Context Although office-based opioid treatment with buprenorphine (OBOT-B) has been successfully implemented in primary care settings in the US, its use has not been reported in homeless patients. Objective To characterize the feasibility of OBOT-B in homeless relative to housed patients. Design A retrospective record review examining treatment failure, drug use, utilization of substance abuse treatment services, and intensity of clinical support by a nurse care manager (NCM) among homeless and housed patients in an OBOT-B program between August 2003 and October 2004. Treatment failure was defined as elopement before completing medication induction, discharge after medication induction due to ongoing drug use with concurrent nonadherence with intensified treatment, or discharge due to disruptive behavior. Results Of 44 homeless and 41 housed patients enrolled over 12 months, homeless patients were more likely to be older, nonwhite, unemployed, infected with HIV and hepatitis C, and report a psychiatric illness. Homeless patients had fewer social supports and more chronic substance abuse histories with a 3- to 6-fold greater number of years of drug use, number of detoxification attempts and percentage with a history of methadone maintenance treatment. The proportion of subjects with treatment failure for the homeless (21%) and housed (22%) did not differ (P = .94). At 12 months, both groups had similar proportions with illicit opioid use [Odds ratio (OR), 0.9 (95% CI, 0.5–1.7) P = .8], utilization of counseling (homeless, 46%; housed, 49%; P = .95), and participation in mutual-help groups (homeless, 25%; housed, 29%; P = .96). At 12 months, 36% of the homeless group was no longer homeless. During the first month of treatment, homeless patients required more clinical support from the NCM than housed patients. Conclusions Despite homeless opioid dependent patients’ social instability, greater comorbidities, and more chronic drug use, office

  17. High-sensitivity analysis of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in plasma and urine by liquid chromatography–mass spectrometry☆

    PubMed Central

    Regina, Karen J.; Kharasch, Evan D.

    2014-01-01

    A new method using ultra-fast liquid chromatography and tandem mass spectrometry (UFLC–MS/MS) was developed for the simultaneous determination of buprenorphine and the metabolites norbuprenorphine, buprenorphine-3β-glucuronide, and norbuprenorphine-3β-glucuronide in plasma and urine. Sample handling, sample preparation and solid-phase extraction procedures were optimized for maximum analyte recovery. All four analytes of interest were quantified by positive ion electrospray ionization tandem mass spectrometry after solid-phase microextraction. The lower limits of quantification in plasma were 1 pg/mL for buprenorphine and buprenorphine glucuronide, and 10 pg/mL for norbuprenorphine and norbuprenorphine glucuronide. The lower limits of quantitation in urine were 10 pg/mL for buprenorphine, norbuprenorphine and their glucuronides. Overall extraction recoveries ranged from 68–100% in both matrices. Interassay precision and accuracy was within 10% for all four analytes in plasma and within 15% in urine. The method was applicable to pharmacokinetic studies of low-dose buprenorphine. PMID:24095872

  18. High-sensitivity analysis of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in plasma and urine by liquid chromatography-mass spectrometry.

    PubMed

    Regina, Karen J; Kharasch, Evan D

    2013-11-15

    A new method using ultra-fast liquid chromatography and tandem mass spectrometry (UFLC-MS/MS) was developed for the simultaneous determination of buprenorphine and the metabolites norbuprenorphine, buprenorphine-3β-glucuronide, and norbuprenorphine-3β-glucuronide in plasma and urine. Sample handling, sample preparation and solid-phase extraction procedures were optimized for maximum analyte recovery. All four analytes of interest were quantified by positive ion electrospray ionization tandem mass spectrometry after solid-phase microextraction. The lower limits of quantification in plasma were 1pg/mL for buprenorphine and buprenorphine glucuronide, and 10pg/mL for norbuprenorphine and norbuprenorphine glucuronide. The lower limits of quantitation in urine were 10pg/mL for buprenorphine, norbuprenorphine and their glucuronides. Overall extraction recoveries ranged from 68-100% in both matrices. Interassay precision and accuracy was within 10% for all four analytes in plasma and within 15% in urine. The method was applicable to pharmacokinetic studies of low-dose buprenorphine. PMID:24095872

  19. DYNAMICS OF OPIOID SUBSTITUTION TREATMENTIN DIFFERENT INITIAL SUBSTANCE USER OPIOID DEPENDENT PATIENTS.

    PubMed

    Todadze, Kh; Mosia, S

    2016-05-01

    Injecting drug user size estimation studies carried out in 2009, 2012 and 2015 revealed growing trends of drug abuse in Georgia:estimated number of people who inject drugs (PWID) have been increased from 40000 and 45000 to 50000. Since Soviet period the most popular injective narcotics have been opioids: home-made opium, heroine, buprenorphine and home-made desomorphine ("Krokodile") replacing each other on the black market. Self-made desomorphine typically contains big amounts of different toxic substances and causes significant somatic disorders, especially skin, bone, blood infections, liver and kidney failure; is highly addictive, associates with frequent injections that enhance injecting-related harm, including the risk of HIV transmission, in comparison with typical opioids. The aim of the study was to determine the effectiveness of opioid substitution treatment (OST) on depression and anxiety in opioid dependent clients with history of different opioid substance use. 104 opioid drug users undergoing OST with intensive psychological counseling have been divided in 5 groups according to the principal opioid drug that was abused during past 6 months before starting treatment: heroine, desomorphine, illicit methadone injectors, illicit buprenorphine injectors, and multiple drug abusers consuming opioids as primary drugs. Level of depression (Beck Depression Inventory), anxiety (Spielberger Anxiety Inventory) as well as clinical symptoms, risky behavior, quality of life (WHO), and other data were measured before starting and after 3, 9, 15, 21 months of treatment. The illegal use of psychotropic-narcotics was checked through random urine-testing 1-2 times per patient per month. In all five groups remarkable decrease of depression and anxiety was observed in comparison with the starting data. Before inclusion desomorphine and poly-drug users had the highest scores of depression and anxiety while buprenorphine users manifested the lowest rate. Improvement of

  20. Effects of Multimodal Analgesia with Low-Dose Buprenorphine and Meloxicam on Fecal Glucocorticoid Metabolites after Surgery in New Zealand White Rabbits (Oryctolagus cuniculus)

    PubMed Central

    Goldschlager, Gregg B; Gillespie, Virginia L; Palme, Rupert; Baxter, Mark G

    2013-01-01

    Despite the increasing use of rabbits as companion animals and models for biomedical research, rabbits have not been extensively studied to identify an efficacious postsurgical analgesic that does not cause systemic complications. The synergy of NSAID and systemic opioids is well-documented, and their combined use reduces the amount of either drug required for adequate analgesia. We measured fecal corticosterone metabolites (FCM) in rabbits after a minimally invasive vascular cut-down procedure. Rabbits received buprenorphine (0.03 mg/kg SC every 12 h for 3 d), meloxicam (0.2 mg/kg SC every 24 h for 3 d), buprenorphine–meloxicam (0.01 mg/kg–0.1 mg/kg SC every 24 h for 3 d), or a single dose of 0.5% bupivacaine (0.5 mL) infused locally at the incision site. By day 3 after surgery, buprenorphine, meloxicam, and bupivacaine groups showed elevated FCM levels, which continued to rise until day 7 and then gradually returned to baseline by day 28. In the buprenorphine–meloxicam group, FCM was relatively unchanged until day 3, when treatment was discontinued, and then began to rise. Rabbits in the buprenorphine–meloxicam group gained more weight over the 28-d study than did those in the other 3 treatment groups. This study shows that in rabbits low-dose buprenorphine administered with meloxicam effectively mitigates the FCM response that develops after surgery without the adverse effects associated with higher doses. PMID:24041213

  1. Budgetary impact analysis of buprenorphine-naloxone combination (Suboxone®) in Spain

    PubMed Central

    2012-01-01

    Background Opioid addiction is a worldwide problem. Agonist opioid treatment (AOT) is the most widespread and frequent pharmacotherapeutic approach. Methadone has been the most widely used AOT, but buprenorphine, a partial μ-opiod agonist and a κ-opiod antagonist, is fast gaining acceptance. The objective was to assess the budgetary impact in Spain of the introduction of buprenorphine-naloxone (B/N) combination. Methods A budgetary impact model was developed to estimate healthcare costs of the addition of B/N combination to the therapeutic arsenal for treating opioid dependent patients, during a 3-year period under the National Health System perspective. Inputs for the model were obtained from the specialized scientific literature. Detailed information concerning resource consumption (drug cost, logistics, dispensing, medical, psychiatry and pharmacy supervision, counselling and laboratory test) was obtained from a local expert panel. Costs are expressed in euros (€, 2010). Results The number of patients estimated to be prescribed B/N combination was 2,334; 2,993 and 3,589 in the first, second and third year respectively. Total budget is €85,766,129; €79,855,471 and €79,137,502 in the first, second and third year for the scenario without B/N combination. With B/N combination the total budget would be €86,589,210; €80,398,259 and €79,708,964 in the first, second and third year of the analyses. Incremental cost/patient comparing the addition of the B/N combination to the scenario only with methadone is €10.58; €6.98 and €7.34 in the first, second and third year respectively. Conclusion Addition of B/N combination would imply a maximum incremental yearly cost of €10.58 per patient compared to scenario only with methadone and would provide additional benefits. PMID:22828157

  2. Antinociceptive effects of epidural buprenorphine or medetomidine, or the combination, in conscious cats.

    PubMed

    Steagall, P V M; Millette, V; Mantovani, F B; Gilbert, P; Luna, S P L; Duke-Novakovski, T

    2009-10-01

    The aim of this study was to compare the antinociceptive effects of epidural buprenorphine (EB), epidural medetomidine (EM) or epidural buprenorphine-medetomidine (EBM). Eight cats were studied. Thermal thresholds (TT) were measured by increasing the temperature of a probe placed on the thorax. Mechanical thresholds (MT) were measured through inflation of a modified blood pressure bladder to the cat's forelimb. After baseline measurements, EB (0.02 mg/kg), EM (0.01 mg/kg) or half of the doses of each drug (EBM) were administered. Data were analysed using anova (P < 0.05) and 95% confidence interval (CI). TT increased from 30 min to 1 h after EB and at 45 min after EM. MT increased from 45 min to 2 h after EB, from 15 min to 1 h after EM and at 30, 45 min and at 2 h after EBM. MT were significantly lower after EB than EM at 30 min. TT were above the upper 95%CI from 15 min to 24 h after EB, from 15 min to 4 h after EM and from 15 min to 8 h after EBM. MT were above the upper 95%CI from 15 min to 5 h, and at 8, 12 and 24 h after EB, from 15 min to 6 h after EM and from 15 min to 6 h and at 12 and 24 h after EBM. All treatments had similar onset. Overall, EB presented longer period of action than EBM and EM. The same magnitude of analgesia was achieved, but with fewer side effects when EBM was compared with EM. PMID:19754915

  3. Opioid withdrawal, craving, and use during and after outpatient buprenorphine stabilization and taper: A discrete survival and growth mixture model

    PubMed Central

    Stotts, Angela L.; Green, Charles; Potter, Jennifer S.; Marino, Elise N.; Walker, Robrina; Weiss, Roger D.; Trivedi, Madhukar

    2014-01-01

    Most patients relapse to opioids within one month of opioid agonist detoxification, making the antecedents and parallel processes of first use critical for investigation. Craving and withdrawal are often studied in relationship to opioid outcomes, and a novel analytic strategy applied to these two phenomena may indicate targeted intervention strategies. Specifically, this secondary data analysis of the Prescription Opioid Addiction Treatment Study used a discrete-time mixture analysis with time-to-first opioid use (survival) simultaneously predicted by craving and withdrawal growth trajectories. This analysis characterized heterogeneity among prescription opioid-dependent individuals (N=653) into latent classes (i.e., latent class analysis [LCA]) during and after buprenorphine/naloxone stabilization and taper. A 4-latent class solution was selected for overall model fit and clinical parsimony. In order of shortest to longest time-to-first use, the 4 classes were characterized as 1) high craving and withdrawal 2) intermediate craving and withdrawal 3) high initial craving with low craving and withdrawal trajectories and 4) a low initial craving with low craving and withdrawal trajectories. Odds ratio calculations showed statistically significant differences in time-to-first use across classes. Generally, participants with lower baseline levels and greater decreases in craving and withdrawal during stabilization combined with slower craving and withdrawal rebound during buprenorphine taper remained opioid-free longer. This exploratory work expanded on the importance of monitoring craving and withdrawal during buprenorphine induction, stabilization, and taper. Future research may allow individually tailored and timely interventions to be developed to extend time-to-first opioid use. PMID:25282598

  4. Sustained-Release Buprenorphine (RBP-6000) Blocks the Effects of Opioid Challenge With Hydromorphone in Subjects With Opioid Use Disorder.

    PubMed

    Nasser, Azmi F; Greenwald, Mark K; Vince, Bradley; Fudala, Paul J; Twumasi-Ankrah, Philip; Liu, Yongzhen; Jones, J P; Heidbreder, Christian

    2016-02-01

    A major goal for the treatment of opioid use disorder is to reduce or eliminate the use of illicit opioids. Buprenorphine, a μ-opioid receptor partial agonist and kappa opioid receptor antagonist, is now being developed as a monthly, sustained-release formulation (RBP-6000). The objective of this study was to demonstrate that RBP-6000 blocks the subjective effects and reinforcing efficacy of the μ-opioid receptor agonist hydromorphone (intramuscularly administered) in subjects with moderate or severe opioid use disorder. Subjects were first inducted and dose stabilized on sublingual buprenorphine/naloxone (8-24 mg daily; dose expressed as the buprenorphine component), then received two subcutaneous injections of RBP-6000 (300 mg) on Day 1 and Day 29. Hydromorphone challenges (6 mg, 18 mg or placebo administered in randomized order) occurred on 3 consecutive days of each study week before and after receiving RBP-6000. Subjects reported their responses to each challenge on various 100-mm Visual Analogue Scales (VAS). Subjects also completed a choice task to assess the reinforcing efficacy of each hydromorphone dose relative to money. At baseline, mean "drug liking" VAS scores for hydromorphone 18 mg and 6 mg versus placebo were 61 mm (95% confidence interval, 52.3-68.9) and 45 mm (95% confidence interval, 37.2-53.6), respectively. After 300 mg RBP-6000 was administered, mean VAS score differences from placebo were less than 10 mm through week 12. The reinforcing efficacy of hydromorphone decreased in a parallel manner. This study demonstrated that RBP-6000 at a 300 mg dose provides durable and potent blockade of the subjective effects and reinforcing efficacy of hydromorphone in subjects with moderate or severe opioid use disorder. PMID:26650971

  5. Clinical effects of buprenorphine on open field behaviour and gait symmetry in healthy and lame weaned piglets.

    PubMed

    Meijer, Ellen; van Nes, Arie; Back, Willem; van der Staay, Franz Josef

    2015-12-01

    Lameness in pigs decreases animal welfare and economic profit for the farmer. An important reason for impaired welfare in lame animals is pain due to lameness. No direct measurement of pain is possible in animals, and methods to indirectly detect and quantify the amount of pain an animal is experiencing are urgently needed. In this study, two methods to assess pain associated with lameness in pigs were evaluated to determine if they were sensitive enough to detect a lameness reduction as an effect of an experimental analgesic medication. Asymmetry associated with lameness was objectively quantified using pressure mat kinetic parameters: peak vertical force (PVF), load rate (LR), vertical impulse (VI) and peak vertical pressure (PVP). Locomotor activity was assessed in an open field test. A dose of 0.04 mg/kg buprenorphine, a strong analgesic, was used to treat 10 lame pigs, while eight other lame pigs, treated with physiological saline solution, served as controls. Buprenorphine decreased lameness-associated asymmetry for pressure mat LR (P = 0.002), VI (P = 0.003) and PVP (P = 0.001) and increased activity of the lame pigs in the open field (P = 0.023), while saline-treated animals did not show any changes in asymmetry and became less active in the open field (P <0.001). It was concluded that measurement of gait asymmetry by pressure mat analysis and locomotor activity in an open field test are both sensitive enough to detect the analgesic effects of buprenorphine when used to treat moderate to severe clinical pain in a relatively small group of affected pigs. The methods used in this study may also provide promising additional tools for future research into early pain recognition and lameness treatment in pigs. PMID:26521014

  6. Issues pertaining to the analysis of buprenorphine and its metabolites by gas chromatography-mass spectrometry.

    PubMed

    Wang, Yu-Shan; Lin, Dong-Liang; Yang, Shu-Ching; Wu, Meng-Yan; Liu, Ray H; Su, Lien-Wen; Cheng, Pai-Sheng; Liu, Chiareiy; Fuh, Ming-Ren

    2010-03-01

    "Substitution therapy" and the use of buprenorphine (B) as an agent for treating heroin addiction continue to gain acceptance and have recently been implemented in Taiwan. Mature and widely utilized gas chromatography-mass spectrometry (GC-MS) technology can complement the low cost and highly sensitive immunoassay (IA) approach to facilitate the implementation of analytical tasks supporting compliance monitoring and pharmacokinetic/pharmacogenetic studies. Issues critical to GC-MS analysis of B and norbuprenorphine (NB) (free and as glucuronides), including extraction, hydrolysis, derivatization, and quantitation approaches were studied, followed by comparing the resulting data against those derived from IA and two types of liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Commercial solid-phase extraction devices, highly effective for recovering all metabolites, may not be suitable for the analysis of free B and NB; acetyl-derivatization products exhibit the most favorable chromatographic, ion intensity, and cross-contribution characteristics for GC-MS analysis. Evaluation of IA, GC-MS, and LC-MS/MS data obtained in three laboratories has proven the 2-aliquot GC-MS protocol effective for the determination of free B and NB and their glucuronides. PMID:20122691

  7. Potentiation of buprenorphine antinociception with ultra-low dose naltrexone in healthy subjects.

    PubMed

    Hay, J L; La Vincente, S F; Somogyi, A A; Chapleo, C B; White, J M

    2011-03-01

    Previous reports have demonstrated greater antinociception following administration of a buprenorphine/naloxone combination compared to buprenorphine alone among healthy volunteers. The aim of the current investigation was to determine whether buprenorphine antinociception could be enhanced with the addition of ultra-low dose naltrexone, using a range of dose ratios. A repeated-measures, double-blind, cross-over trial was undertaken with 10 healthy participants. The effects of each buprenorphine:naltrexone ratio (100:1, 133:1, 166:1, and 200:1) on cold pressor tolerance time and respiration were compared to the effects of buprenorphine only. The 166:1 ratio was associated with significantly greater tolerance time to cold pressor pain than buprenorphine alone. Minimal respiratory depression and few adverse events were observed in all conditions. These findings suggest that, as previously described with naloxone, the addition of ultra-low dose naltrexone can enhance the antinociceptive effect of buprenorphine in humans. This potentiation is dose-ratio dependent and occurs without a concomitant increase in adverse effects. PMID:20728384

  8. Crushed and Injected Buprenorphine Tablets: Characteristics of Princeps and Generic Solutions

    PubMed Central

    Bouquié, Régis; Wainstein, Laura; Pilet, Paul; Mussini, Jean-Marie; Deslandes, Guillaume; Clouet, Johann; Dailly, Eric; Jolliet, Pascale; Victorri-Vigneau, Caroline

    2014-01-01

    Self-injection of high-dose buprenorphine is responsible for well-described complications. In 2011, we have been alerted by unusual but serious cutaneous complication among injection buprenorphine users. A prospective data collection identified 30 cases of necrotic cutaneous lesions after injection of filtered buprenorphine solution, among which 25 cases occurred following injection of buprenorphine generics. The main goal of our study was to put forward particularities that could explain the cutaneous complications, by qualitatively and quantitatively confronting particles present in Subutex and generics solutions. We used the same protocol that injected-buprenorphine users: generic or subutex tablets were crushed in sterile water and filtered through 2 filters commonly used (cotton-pad and sterifilt). Solutions were analyzed by laser granulometry, flow cytometry and scanning electron microscopy. We have highlighted the wide variation of the quantity and the size of the particles present in solution between the two drugs after cotton-pad filtration. The proportion of particles <10 µm is systematically higher in the generic solutions than with Subutex. All of the insoluble particles found in generic solutions contain silica, whereas non- organic element was to be identified in the insoluble particles of Subutex. One skin biopsy obtained from one patient who developed a necrotic lesion after intravenous injection of filtrated solution of buprenorphine generic, shows non-organic elements. Identification of particles in situ enables us to confirm the presence of silica in the biopsy. Actually the monitoring of patient receiving generic of buprenorphine must be strengthened. PMID:25474108

  9. Comparison of intravenous buprenorphine and methadone self-administration by recently detoxified heroin-dependent individuals.

    PubMed

    Comer, Sandra D; Sullivan, Maria A; Walker, Ellen A

    2005-12-01

    Although buprenorphine is used worldwide as a safe and effective maintenance medication for opioid dependence, some countries have reported a growing incidence of abuse of this medication. Buprenorphine is considered to have lower abuse potential because of its partial agonist profile, but no studies have directly compared the reinforcing effects of buprenorphine with those of full mu opioid agonists in humans. The present double-blind, placebo-controlled inpatient study compared the reinforcing and subjective effects of intravenously administered buprenorphine (0.5, 2, and 8 mg) and methadone (5, 10, and 20 mg). Participants (n = 6) were detoxified from heroin during the first 1 to 2 weeks after admission. During subsequent weeks, participants received a sample drug dose and $20 on Monday, and they could self-administer either the sampled dose or $20 during one choice session per day on Thursday and Friday. Participants responded under a modified progressive ratio schedule during each choice session. All active doses maintained higher progressive ratio break points (largest completed ratio) than placebo. There were no significant differences in break point values between buprenorphine and methadone or among the different doses of drug. However, several subjective ratings, including "good drug effect", "high", and "liking" dose-dependently increased after administration of buprenorphine and methadone. The peak ratings for these effects did not significantly differ for the two drugs. These results demonstrate that under these experimental conditions, buprenorphine and methadone were equally effective in producing reinforcing and subjective effects. PMID:16144974

  10. Availability of buprenorphine on the Internet for purchase without a prescription

    PubMed Central

    Bachhuber, Marcus A.; Cunningham, Chinazo O.

    2012-01-01

    Background Use of illicit buprenorphine is increasingly recognized, but it is unknown if the Internet currently represents an accessible source. Methods A series of Internet searches were conducted. Twenty searches were performed on two different search engines. The first 100 results of each search were classified into categories based on content. All Internet pharmacies were searched for buprenorphine preparations and if available, sites were examined to determine if a prescription was required for purchase, for the cost of buprenorphine, the geographical origin of the pharmacy, and evidence of validation by an online pharmacy verification service. Results Of the 2,000 links examined, 1422 were unique. Six percent of links were to illicit commercial sites, 2% were to legitimate commercial sites, and 2% were to illicit portal sites, which contained links to many illicit commercial sites. Twenty pharmacies offering buprenorphine for purchase without a prescription were identified. The monthly cost of a typical starting dose of 2 mg buprenorphine daily ranged between $232 and $1,163 USD. No pharmacies were listed by online pharmacy verification services. Conclusion Twenty online pharmacies advertising buprenorphine formulations for sale without a prescription were identified. Prices varied widely between illicit pharmacies but were uniformly more expensive than legitimate pharmacies. Illicitly obtained buprenorphine formulations appear to be relatively inaccessible and at high cost on the Internet. PMID:23201172

  11. Substituted Indazoles as Nav1.7 Blockers for the Treatment of Pain.

    PubMed

    Frost, Jennifer M; DeGoey, David A; Shi, Lei; Gum, Rebecca J; Fricano, Meagan M; Lundgaard, Greta L; El-Kouhen, Odile F; Hsieh, Gin C; Neelands, Torben; Matulenko, Mark A; Daanen, Jerome F; Pai, Madhavi; Ghoreishi-Haack, Nayereh; Zhan, Cenchen; Zhang, Xu-Feng; Kort, Michael E

    2016-04-14

    The genetic validation for the role of the Nav1.7 voltage-gated ion channel in pain signaling pathways makes it an appealing target for the potential development of new pain drugs. The utility of nonselective Nav blockers is often limited due to adverse cardiovascular and CNS side effects. We sought more selective Nav1.7 blockers with oral activity, improved selectivity, and good druglike properties. The work described herein focused on a series of 3- and 4-substituted indazoles. SAR studies of 3-substituted indazoles yielded analog 7 which demonstrated good in vitro and in vivo activity but poor rat pharmacokinetics. Optimization of 4-substituted indazoles yielded two compounds, 27 and 48, that exhibited good in vitro and in vivo activity with improved rat pharmacokinetic profiles. Both 27 and 48 demonstrated robust activity in the acute rat monoiodoacetate-induced osteoarthritis model of pain, and subchronic dosing of 48 showed a shift to a lower EC50 over 7 days. PMID:27015369

  12. Intravenous use of illicit buprenorphine/naloxone to reverse an acute heroin overdose.

    PubMed

    Yokell, Michael A; Zaller, Nickolas D; Green, Traci C; McKenzie, Michelle; Rich, Josiah D

    2012-01-01

    A case of heroin overdose reversed through the intravenous (IV) administration of a crushed sublingual tablet of buprenorphine/naloxone (Suboxone) by a lay responder is described. Although the sublingual administration of buprenorphine/naloxone to reverse an overdose has been reported elsewhere, this is the first report of IV administration. Healthcare professionals should be aware that injection drug users may respond to an opioid overdose by injecting buprenorphine/naloxone and should consequently counsel all opioid-using patients on the proper response to an overdose. Physicians should also consider prescribing naloxone to at-risk patients. The work of community-based naloxone distribution programs should be expanded. PMID:22479887

  13. Pharmacokinetics of 2 Formulations of Buprenorphine in Macaques (Macaca mulatta and Macaca fascicularis)

    PubMed Central

    Nunamaker, Elizabeth A; Halliday, Lisa C; Moody, David E; Fang, Wenfang B; Lindeblad, Matthew; Fortman, Jeffrey D

    2013-01-01

    Buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. The purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species (M. mulatta and M. fascicularis) by using mass spectrometry. The pharmacokinetics did not differ significantly between species, and buprenorphine was dose-proportional at the tested doses. The low and high doses of buprenorphine had elimination half-lives of 2.6 ± 0.7 and 5.3 ± 2.0 h, respectively, but the low-dose data were constrained by the sensitivity of the analytical method. Sustained-release buprenorphine had an elimination half-life of 42.6 ± 26.2 h. The AUC0-Tlast of buprenorphine were 9.1 ± 4.3 and 39.0 ± 25.1 ng×h/mL for the low and high doses, respectively, and sustained-release buprenorphine had an AUC0-Tlast of 177 ± 74 ng×h/mL. Assuming a hypothesized therapeutic buprenorphine plasma concentration threshold of 0.1 ng/mL in macaques, these results suggest that buprenorphine doses of 0.01 mg/kg IM should be administered every 6 to 8 h, whereas doses of 0.03 mg/kg IM can be administered every 12 h. These results further demonstrate that a single 0.2-mg/kg SC injection of sustained-release buprenorphine maintains plasma concentrations above 0.1 ng/mL for 5 d in macaques. These findings support a new dosing strategy using sustained-release buprenorphine to improve pain management, decrease animal stress, improve animal welfare, and simplify the postoperative management of nonhuman primates in laboratory animal and zoological settings. PMID:23562033

  14. Solvent substitution

    SciTech Connect

    Not Available

    1990-01-01

    The DOE Environmental Restoration and Waste Management Office of Technology Development and the Air Force Engineering and Services Center convened the First Annual International Workshop on Solvent Substitution on December 4--7, 1990. The primary objectives of this joint effort were to share information and ideas among attendees in order to enhance the development and implementation of required new technologies for the elimination of pollutants associated with industrial use of hazardous and toxic solvents; and to aid in accelerating collaborative efforts and technology transfer between government and industry for solvent substitution. There were workshop sessions focusing on Alternative Technologies, Alternative Solvents, Recovery/Recycling, Low VOC Materials and Treatment for Environmentally Safe Disposal. The 35 invited papers presented covered a wide range of solvent substitution activities including: hardware and weapons production and maintenance, paint stripping, coating applications, printed circuit boards, metal cleaning, metal finishing, manufacturing, compliance monitoring and process control monitoring. This publication includes the majority of these presentations. In addition, in order to further facilitate information exchange and technology transfer, the US Air Force and DOE solicited additional papers under a general Call for Papers.'' These papers, which underwent review and final selection by a peer review committee, are also included in this combined Proceedings/Compendium. For those involved in handling, using or managing hazardous and toxic solvents, this document should prove to be a valuable resource, providing the most up-to-date information on current technologies and practices in solvent substitution. Individual papers are abstracted separated.

  15. BU08073 a buprenorphine analogue with partial agonist activity at μ-receptors in vitro but long-lasting opioid antagonist activity in vivo in mice

    PubMed Central

    Khroyan, T V; Wu, J; Polgar, W E; Cami-Kobeci, G; Fotaki, N; Husbands, S M; Toll, L

    2015-01-01

    BACKGROUND AND PURPOSE Buprenorphine is a potent analgesic with high affinity at μ, δ and κ and moderate affinity at nociceptin opioid (NOP) receptors. Nevertheless, NOP receptor activation modulates the in vivo activity of buprenorphine. Structure activity studies were conducted to design buprenorphine analogues with high affinity at each of these receptors and to characterize them in in vitro and in vivo assays. EXPERIMENTAL APPROACH Compounds were tested for binding affinity and functional activity using [35S]GTPγS binding at each receptor and a whole-cell fluorescent assay at μ receptors. BU08073 was evaluated for antinociceptive agonist and antagonist activity and for its effects on anxiety in mice. KEY RESULTS BU08073 bound with high affinity to all opioid receptors. It had virtually no efficacy at δ, κ and NOP receptors, whereas at μ receptors, BU08073 has similar efficacy as buprenorphine in both functional assays. Alone, BU08073 has anxiogenic activity and produces very little antinociception. However, BU08073 blocks morphine and U50,488-mediated antinociception. This blockade was not evident at 1 h post-treatment, but is present at 6 h and remains for up to 3–6 days. CONCLUSIONS AND IMPLICATIONS These studies provide structural requirements for synthesis of ‘universal’ opioid ligands. BU08073 had high affinity for all the opioid receptors, with moderate efficacy at μ receptors and reduced efficacy at NOP receptors, a profile suggesting potential analgesic activity. However, in vivo, BU08073 had long-lasting antagonist activity, indicating that its pharmacokinetics determined both the time course of its effects and what receptor-mediated effects were observed. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24903063

  16. Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting.

    PubMed

    Hedenqvist, Patricia; Trbakovic, Amela; Thor, Andreas; Ley, Cecilia; Ekman, Stina; Jensen-Waern, Marianne

    2016-08-01

    In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10×10mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n=9) or buprenorphine plus saline (n=9) postoperatively. Buprenorphine was administered subcutaneously every 6h for 3days in a tapered dose (0.05-0.01mg/kg) and carprofen (5mg/kg) or saline administered subcutaneously 1h before, and daily for 4days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 4.3 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5mg/kg carprofen once daily for 5days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation. PMID:27473985

  17. Dexamethasone hepatic induction in rats subsequently treated with high dose buprenorphine does not lead to respiratory depression

    SciTech Connect

    Hreiche, Raymond; Megarbane, Bruno . E-mail: bruno-megarbane@wanadoo.fr; Pirnay, Stephane; Borron, Stephen W.; Monier, Claire; Risede, Patricia; Milan, Nathalie; Descatoire, Veronique; Pessayre, Dominique; Baud, Frederic J.

    2006-12-15

    In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg{sup -1} was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg{sup -1} buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, using whole body plethysmography (N = 24) and arterial blood gases (N = 12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3] + buprenorphine [day 4]), (dexamethasone solvent [days 1-3] + buprenorphine [day 4]), (dexamethasone [days 1-3] + buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3] + buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P < 0.001), without significant effects on the respiratory frequency, the tidal volume, the minute volume, or arterial blood gases. In dexamethasone-pretreated rats, there was no significant alteration in the respiratory parameters, despite CYP3A induction and significant increase of the ratio of plasma norbuprenorphine-to-buprenorphine concentrations. In conclusion, dexamethasone did not modify the effects of 30 mg kg{sup -1} buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts.

  18. Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus).

    PubMed

    Seymour, Travis L; Adams, Sean C; Felt, Stephen A; Jampachaisri, Katechan; Yeomans, David C; Pacharinsak, Cholawat

    2016-01-01

    Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain. PMID:27177563

  19. Effect of low-level laser treatment of tissue-engineered skin substitutes: contraction of collagen lattices

    NASA Astrophysics Data System (ADS)

    Ho, Gideon; Barbenel, Joseph; Grant, M. Helen

    2009-05-01

    Fibroblast-populated collagen lattices (FPCL) are widely used in tissue-engineered artificial skin substitutes, but their main drawback is that interaction of fibroblasts and matrix causes contraction of the lattice, reducing it to about 20% of its original area. The effect of low-level laser treatment (LLLT) on the behavior of 3T3 fibroblasts seeded in collagen lattices containing 20% chondroitin-6-sulphate was investigated to determine whether LLLT could control the contraction of FPCL. A He-Ne laser was used at 632.8 nm to deliver a 5-mW continuous wave with fluences from 1 to 4 J/cm2. Laser treatment at 3 J/cm2 increased contraction of collagen lattices in the absence of cells but decreased contraction of cell seeded lattices over a 7-day period. The effect was energy dependent and was not observed at 1, 2, or 4 J/cm2. There was no alteration in fibroblast viability, morphology, or mitochondrial membrane potential after any laser treatments, but the distribution of actin fibers within the cells and collagen fibers in the matrices was disturbed at 3 J/cm2. These effects contribute to the decrease in contraction observed. LLLT may offer a means to control contraction of FPCL used as artificial skin substitutes.

  20. [Is the availability of buprenorphine/naloxone therapy for opioid-dependent inmates a necessity? ].

    PubMed

    Marco, A; López-Burgos, A; García-Marcos, L; Gallego, C; Antón, J J; Errasti, A

    2013-02-01

    Agonist therapy (OAT) programs in combination with a psychosocial approach are the most effective way to prevent relapse in opioid-dependent patients. These programs reduce morbidity and risk behaviours for HIV transmission and other infections, improve quality of life and retention in treatment, and have a positive impact on antisocial behaviour. They are therefore very useful for prisoners with a history of opiate use. OATs based on buprenorphine/naloxone (B/N), along with others using methadone, are currently available in Spain. Diversified treatment offers an alternative treatment for opioid dependence that is more personalized and tailored to the patient's characteristics. As regards effectiveness, both drugs are very similar, but B/N shows a better safety profile and fewer drug-drug interactions and can be dispensed in pharmacies once the patient is released, which can assist with the patient' social reintegration. B/N treatment is more expensive than methadone. It is advisable to have different modes of OAT. These should be prescribed according to the characteristics and needs of each case, without incarceration impeding the right to drug treatment, which should be similar to that performed outside prison. PMID:24270319

  1. Buprenorphine as a safe alternative to methadone in a patient with acquired long QT syndrome: a case report.

    PubMed

    de Jong, I M; de Ruiter, G S

    2013-05-01

    A 52-year-old man with a medical history of intravenous drug abuse was admitted to our hospital with syncope due to torsades de pointes (TdP). Two days earlier, he had used methadone. The electrocardiogram showed a prolonged corrected QT interval (QTc) of 600 ms. Continuous telemetry observation showed multiple episodes of TdP. The patient was diagnosed with bradyarrhythmia-induced TdP with acquired long QT syndrome resulting from methadone use. The QTc normalised within 2 weeks after discontinuation of the methadone. In this case of a patient with opioid dependency, there is a reasonable risk of repeated methadone use. Therefore, implantable cardioverter defibrillator or pacemaker implantation is justified but risky because of possible infections when using intravenous drugs. Given the high mortality rates seen in untreated illicit opioid users, this patient needs an alternative pharmacological treatment. Buprenorphine is an opiate-receptor agonist associated with less QTc prolongation. The patient was referred to a rehab clinic and treated with an oral combination of buprenorphine and naloxone (Suboxone). During this therapy, his QTc remained normal. PMID:22020456

  2. Treatment of intractable skin ulcers caused by vascular insufficiency with allogeneic cultured dermal substitute: a report of eight cases.

    PubMed

    Taniguchi, Tomonori; Amoh, Yasuyuki; Tanabe, Kenichi; Katsuoka, Kensei; Kuroyanagi, Yoshimitsu

    2012-03-01

    Chronic leg ulcers have various causes and can be difficult to treat, although topical treatments, including basic fibroblast growth factor and PGE1, have been used. We applied an allogeneic cultured dermal substitute (CDS) to eight patients with intractable ulcers. The patients had various underlying diseases, including diabetes mellitus, systemic lupus erythematosus, antiphospholipid syndrome, necrobiosis lipoidica, stasis dermatitis, livedo vasculopathy, and rheumatoid arthritis. The CDS was prepared by seeding cultured human fibroblasts on a spongy matrix consisting of hyaluronic acid and atelocollagen. Good clinical results were achieved, as demonstrated by reepithelization, healthy granulation tissue formation, and a subsequent decrease in wound size. Daily dressing changes became unnecessary when the allogeneic CDS was used. Based on these results, we suggest that CDS may be useful for the treatment of intractable skin ulcers. PMID:21861088

  3. The Severity, Frequency, and Variety of Crime in Heroin-Dependent Prisoners Enrolled in a Buprenorphine Clinical Trial

    PubMed Central

    Gordon, Michael S.; Kinlock, Timothy W.; Schwartz, Robert P.; Couvillion, Kathryn A.; O’Grady, Kevin E.

    2014-01-01

    Data were obtained on four dimensions of criminal activity (frequency, variety, severity, and income) from male and female prisoners (N = 200) with preincarceration heroin dependence who participated in a randomized clinical trial of buprenorphine treatment. The article examines the above-mentioned dimensions of crime and their relationships with demographic characteristics, substance use, legitimate employment, drug treatment episodes, and psychological problems. Results largely show several important similarities to results on previous prison inmate cohorts with histories of heroin addiction, although the present sample may have more of a tendency toward violent crime than earlier cohorts of heroin-dependent offenders. This study’s findings may have implications for the design of appropriate treatment interventions for prisoners with preincarceration heroin dependence that address not only substance use but also criminal activity. PMID:25392564

  4. Sublingual Buprenorphine/Naloxone Precipitated Withdrawal in Subjects Maintained on 100 mg of Daily Methadone*

    PubMed Central

    Rosado, James; Walsh, Sharon L.; Bigelow, George E.; Strain, Eric C.

    2007-01-01

    Rationale Acute doses of buprenorphine can precipitate withdrawal in opioid dependent persons. The likelihood of this withdrawal increases as a function of the level of physical dependence. Objectives To test the acute effects of sublingual buprenorphine/naloxone tablets in volunteers with a higher level of physical dependence. The goal was to identify a dose that would precipitate withdrawal (Phase 1), then determine if withdrawal could be attenuated by splitting this dose (Phase 2). Methods Residential laboratory study; subjects (N=16) maintained on 100 mg per day of methadone. Phase 1: Randomized, double blind, triple dummy, within subject study. Conditions were sublingual buprenorphine/naloxone (4/1, 8/2, 16/4, 32/8 mg), intramuscular naloxone (0.2 mg), oral methadone (100 mg), or placebo. Medication conditions were randomized, but buprenorphine/naloxone doses were ascending within the randomization. Phase 2: Conditions were methadone, placebo, naloxone, 100% of the buprenorphine/naloxone dose that precipitated withdrawal in Phase 1 (full dose), and 50% of this dose administered twice in a session (split dose). Analyses covaried by trough methadone serum levels. Results Six subjects did not complete the study. Of the ten who completed, three tolerated up to 32/8 mg of buprenorphine/naloxone without evidence of precipitated withdrawal. For the seven completing both phases, split doses generally produced less precipitated withdrawal compared to full doses. Conclusions There is considerable between subject variability in sensitivity to buprenorphine's antagonist effects. Low, repeated doses of buprenorphine/naloxone (e.g., 2/0.5 mg) may be an effective mechanism for safely dosing this medication in persons with higher levels of physical dependence. PMID:17517480

  5. Pharmacokinetics and Antinociceptive Activity of Sustained-Release Buprenorphine in Sheep

    PubMed Central

    Walkowiak, Krista J; Graham, Melanie L

    2015-01-01

    Buprenorphine is a potent analgesic commonly administered to alleviate pain in sheep used in research. Sustained-release buprenorphine (SRB) is an alternative to conventional buprenorphine hydrochloride (which must be injected repeatedly). To compare SRB with a typical conventional buprenorphine regimen (0.03 mg/kg every 8 h for 72 h), we used a simple 1:1 conversion to calculate a total SRB dose of 0.27 mg/kg per injection. The pharmacokinetics and thermal nociceptive effects of SRB were analyzed in 4 healthy adult sheep after a single intramuscular injection plus a washout period then a single subcutaneous injection. For both routes in all 4 sheep, plasma buprenorphine concentrations exceeded 0.1 ng/mL, considered the minimal threshold for therapeutic benefit, after 12 h and maintained a steady state for at least 72 h Likewise, for both routes in all sheep, thermal thresholds increased significantly between baseline and 12 h; lack of response persisted for at least 72 h. The average maximal plasma buprenorphine concentrations and bioavailability were similar for both routes. No clinical adverse effects occurred. Using a dose equivalent to the total course of conventional buprenorphine, this pilot study suggests that SRB is a well-tolerated, effective, and long-acting analgesic that can be administered as a single intramuscular or subcutaneous injection. SRB confers steady plasma concentrations and continuous analgesia in thermal nociception for at least 72 h. When compared with conventional buprenorphine, SRB has considerable advantages in improving wellbeing by minimizing handling-associated stress of repeated injection and limiting the likelihood of end-of-dose breakthrough pain. PMID:26632786

  6. A Marcus Treatment of Rate Constants for Protonation of Ring-Substituted α-Methoxystyrenes

    PubMed Central

    Richard, John P.; Williams, Kathleen B.

    2008-01-01

    Rate and equilibrium constants were determined for protonation of ring-substituted α-methoxystyrenes by hydronium ion and by carboxylic acids to form the corresponding ring-substituted α-methyl α-methoxybenzyl carbocations at 25 ° C and I = 1.0 (KCl). The thermodynamic barrier to carbocation formation increases by14.5 kcal/mol as the phenyl ring substituent(s) is changed from 4-MeO- to 3,5-di-NO2-, and as the carboxylic acid is changed from dichloroacetic to acetic acid. The Brønsted coefficient α for protonation by carboxylic acids increases from 0.67 to 0.77 over this range of phenyl ring substituents and the Brønsted coefficient β for proton transfer increases from 0.63 to 0.69 as the carboxylic acid is changed from dichloroacetic to acetic acid. The change in these Brønsted coefficients with changing reaction driving force, ∂α∕∂ΔGavo=∂β∕∂ΔGavo=1∕8Λ=0.011 is used to calculate a Marcus intrinsic reaction barrier of Λ = 11 kcal/mol which is close to the barrier of 13 kcal/mol for thermoneutral proton transfer between this series of acids and bases. The value of α = 0.66 for thermoneutral proton transfer is greater than α = 0.50 required by a reaction that follows the Marcus equation. This elevated value of β may be due to an asymmetry in the reaction coordinate that arises from the difference in the intrinsic barriers for proton transfer at the oxygen acid reactant and resonance stabilized carbon acid product. PMID:17488079

  7. Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy greyhound dogs.

    PubMed

    KuKanich, B; Allen, P

    2014-12-01

    The purpose of this study was to compare the pharmacokinetics of two highly protein-bound, lipophilic opioid drugs. Fentanyl (10 μg/kg) and buprenorphine (20 μg/kg) were administered intravenously (IV) to six healthy greyhound dogs (three males and three females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry, and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL·min/kg) was faster than buprenorphine (10.3 mL·min/kg). The terminal half-life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including octanol-water partition coefficient and pKa, the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95-98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs. PMID:24684621

  8. Chronic buprenorphine reduces the response to sucrose-associated cues in non food-deprived rats.

    PubMed

    Hood, Suzanne; Sorge, Robert E; Stewart, Jane

    2007-03-01

    The mechanisms through which buprenorphine (BUP), a mixed opioid agonist-antagonist, reduces both heroin and cocaine taking remain unclear. Evidence suggests that chronic exposure to BUP blunts drug seeking by attenuating the salience of drug-associated cues. Here, we examined the effect of chronic BUP treatment (osmotic minipumps, 3.0 mg/kg/day) in rats on responding for sucrose pellets and associated cues on FR1, FR5, and PR schedules and on extinction and reinstatement of sucrose seeking by sucrose priming. The effect of chronic BUP treatment on the dopamine (DA) response in the nucleus accumbens (NAc) to sucrose pellets and to lab chow was also measured using in vivo microdialysis. Whereas chronic BUP treatment had only a modest effect on pellet intake on the FR1 schedule, it significantly reduced responding at the outset of sessions and reduced lever pressing during sucrose-associated cue presentations. No effect was observed in the FR5 or PR schedules. BUP slightly reduced responding during extinction and significantly reduced reinstatement. Chronic BUP did not alter the NAc DA response to either sucrose pellets or lab chow, although it did significantly increase basal DA. Consistent with previous studies with heroin and cocaine, chronic BUP reduced responding in the presence of reward-related cues. PMID:17346785

  9. Production and validation of model iron-tannate dyed textiles for use as historic textile substitutes in stabilisation treatment studies

    PubMed Central

    2012-01-01

    Background For millennia, iron-tannate dyes have been used to colour ceremonial and domestic objects shades of black, grey, or brown. Surviving iron-tannate dyed objects are part of our cultural heritage but their existence is threatened by the dye itself which can accelerate oxidation and acid hydrolysis of the substrate. This causes many iron-tannate dyed textiles to discolour and decrease in tensile strength and flexibility at a faster rate than equivalent undyed textiles. The current lack of suitable stabilisation treatments means that many historic iron-tannate dyed objects are rapidly crumbling to dust with the knowledge and value they hold being lost forever. This paper describes the production, characterisation, and validation of model iron-tannate dyed textiles as substitutes for historic iron-tannate dyed textiles in the development of stabilisation treatments. Spectrophotometry, surface pH, tensile testing, SEM-EDX, and XRF have been used to characterise the model textiles. Results On application to textiles, the model dyes imparted mid to dark blue-grey colouration, an immediate tensile strength loss of the textiles and an increase in surface acidity. The dyes introduced significant quantities of iron into the textiles which was distributed in the exterior and interior of the cotton, abaca, and silk fibres but only in the exterior of the wool fibres. As seen with historic iron-tannate dyed objects, the dyed cotton, abaca, and silk textiles lost tensile strength faster and more significantly than undyed equivalents during accelerated thermal ageing and all of the dyed model textiles, most notably the cotton, discoloured more than the undyed equivalents on ageing. Conclusions The abaca, cotton, and silk model textiles are judged to be suitable for use as substitutes for cultural heritage materials in the testing of stabilisation treatments. PMID:22616934

  10. The politics of place(ment): problematising the provision of hepatitis C treatment within opiate substitution clinics.

    PubMed

    Rance, Jake; Newland, Jamee; Hopwood, Max; Treloar, Carla

    2012-01-01

    The hepatitis C virus (HCV) epidemic is a significant public health challenge in Australia. Current initiatives to expand access to HCV treatment focus on opiate substitution therapy (OST) settings where the prevalence of hepatitis C among clients is high. In Australia, the provision of OST for many clients is via large clinics, with an estimated median of 150 clients per service. Conceptually informed by the work of Michel Foucault, our analysis of the proposed integrated treatment model focuses on the critical but overlooked question of organisational culture and power operating within OST. We argue that the specific context of OST not merely reflects but actively participates in the political economy of social exclusion via which the socio-spatial segregation and stigmatisation of the service user as 'drug user' is enacted. This paper analyses data collected from two samples during 2008/9: OST clients living in New South Wales, Australia and a range of OST health professionals working in Australian settings. In total, 27 interviews were conducted with current OST clients; 19 by phone and 8 face-to-face. One focus group and 16 telephone interviews were conducted with OST health professionals. Our analysis of key themes emerging from the interview data suggests that the successful introduction of HCV treatment within the OST clinic is not a given. We are concerned that particular areas of tension, if not explicit contradiction, have been overlooked in current research and debates informing the proposed combination treatment model. We question the appropriateness of co-locating a notoriously arduous, exacting treatment (HCV) within the highly surveillant and regulatory environment of OST. While applauding the intention to improve access to HCV care and treatment for people who inject drugs we caution against a treatment model that risks further entrenching (socio-spatial) stigmatisation amongst those already experiencing significant marginalisation. PMID:22133583

  11. Evaluation of medetomidine, ketamine and buprenorphine for neutering feral cats.

    PubMed

    Harrison, Kelly A; Robertson, Sheilah A; Levy, Julie K; Isaza, Natalie M

    2011-12-01

    A combination of medetomidine (M, 100 μg/kg), ketamine (K, 10 mg/kg) and buprenorphine (B, 10 μg/kg), administered by intramuscular injection, was evaluated for spaying and castration (neutering) of feral cats (n = 101). Eleven animals (11%) required supplemental anesthesia (isoflurane by mask) to maintain an adequate plane of surgical anesthesia. Atipamezole (A, 125 μg/kg) was administered subcutaneously at the completion of surgery. All cats recovered from surgery and were released the following day. A hemoglobin saturation (SpO(2)) value of < 95% was recorded at least once during anesthesia in all cats. This MKB combination can be used in a feral cat sterilization clinic, but isoflurane supplementation may be necessary. Further research is indicated to determine the clinical significance of the low SpO(2) values associated with this anesthetic regimen. PMID:21885310

  12. Improving Adherence to HIV Quality of Care Indicators in Persons With Opioid Dependence: The Role of Buprenorphine

    PubMed Central

    Korthuis, P. Todd; Fiellin, David A.; Fu, Rongwei; Lum, Paula J.; Altice, Frederick L.; Sohler, Nancy; Tozzi, Mary J.; Asch, Steven M.; Botsko, Michael; Fishl, Margaret; Flanigan, Timothy P.; Boverman, Joshua; McCarty, Dennis

    2011-01-01

    Background Opioid-dependent HIV-infected patients are less likely to receive HIV quality of care indicators (QIs) compared with nondependent patients. Buprenorphine/naloxone maintenance therapy (bup/nx) could affect the quality of HIV care for opioid-dependent patients. Methods We abstracted 16 QIs from medical records at nine HIV clinics 12 months before and after initiation of bup/nx versus other treatment for opioid dependence. Summary quality scores (number of QIs received/number eligible × 100) were calculated. We compared change in QIs and summary quality scores in patients receiving bup/nx versus other participants. Results One hundred ninety-four of 268 participants (72%) received bup/nx and 74 (28%) received other treatment. Mean summary quality scores increased over 12 months for participants receiving bup/nx (45.6% to 51.6%, P < 0.001) but not other treatment (48.6% to 47.8%, P = 0.788). Bup/nx participants experienced improvements in six of 16 HIV QIs versus three of 16 QIs in other participants. Improvements were mostly in preventive and monitoring care domains. In multivariable analysis, bup/nx was associated with improved summary quality score (β 8.55; 95% confidence interval, 2.06–15.0). Conclusions In this observational cohort study, HIV-infected patients with opioid dependence received approximately half of HIV QIs at baseline. Buprenorphine treatment was associated with improvement in HIV QIs at 12 months. Integration of bup/nx into HIV clinics may increase receipt of high-quality HIV care. Further research is required to assess the effect of improved quality of HIV care on clinical outcomes. PMID:21317600

  13. A Clinical Trial Comparing Tapering Doses of Buprenorphine with Steady Doses for Chronic Pain and Co-existent Opioid Addiction

    PubMed Central

    Blondell, Richard D.; Ashrafioun, Lisham; Dambra, Christina M.; Foschio, Elisa M.; Zielinski, Amy L.; Salcedo, Daniel M.

    2009-01-01

    Objectives Effective strategies are needed to manage individuals with chronic non-cancer pain and coexistent opioid addiction. This study compared opioid discontinuation and opioid replacement protocols. Methods We planned to enroll 60 individuals into an open-label trial who had been treated with opioids for chronic non-cancer pain, and who also had opioid addiction. Participants were randomly assigned to one of two 6-month treatment protocols of buprenorphine/naloxone sublingual tablets: 1) tapering doses for opioid weaning or “detoxification” (active comparator group) or 2) steady doses for opioid replacement (experimental group). They were followed monthly for the study outcomes: completion of the 6-month treatment protocol and self-reported pain control, physical functioning, alcohol consumption and illicit drug use. Results Enrollment was terminated after enrolling 12 participants because none of the 6 assigned to receive tapering doses could successfully complete the protocol (5 were given steady doses and 1 was admitted to an inpatient chemical dependency treatment program); whereas, of the 6 assigned to receive steady doses, 5 completed the protocol (1 withdrew). This difference between the 2 treatment conditions was significant (P = 0.015). Of the 10 participants who completed the 6 month follow-up, 8 reported improved pain control and physical functioning and 5 used alcohol and/or illicit drugs. Conclusions We conclude that over 6 months, these participants with chronic pain and co-existent opioid addiction were more likely to adhere to an opioid replacement protocol than an opioid weaning protocol and that opioid replacement therapy with steady doses of buprenorphine/naloxone is associated with improved pain control and physical functioning. PMID:20959867

  14. Substitutes or complements? Diagnosis and treatment with non-conventional and conventional medicine

    PubMed Central

    Tavares, Aida Isabel

    2015-01-01

    Background: Portugal has a strong tradition of conventional western healthcare. So it provides a natural case study for the relationship between Complementary/Alternative Medicine (CAM) and Western Medicine (WM). This work aims to test the relationship between CAM and WM users in the diagnosis and treatment stages and to estimate the determinants of CAM choice. Methods: The forth Portuguese National Health Survey is employed to estimate two single probit models and obtain the correlation between the consumption of CAM and WM medicines in the diagnosis and treatment stages. Results: Firstly, both in the diagnosis and the treatment stage, CAM and WM are seen to be complementary choices for individuals. Secondly, self-medication also shows complementarity with the choice of CAM treatment. Thirdly, education has a non-linear relationship with the choice of CAM. Finally, working status, age, smoking and chronic disease are determinant factors in the decision to use CAM. Conclusion: The results of this work are relevant to health policy-makers and for insurance companies. Patients need freedom of choice and, for the sake of safety and efficacy of treatment, WM and CAM healthcare ought to be provided in a joint and integrated health system. PMID:25844385

  15. Patterns of free (unconjugated) buprenorphine, norbuprenorphine, and their glucuronides in urine using liquid chromatography-tandem mass spectrometry.

    PubMed

    McMillin, Gwendolyn A; Davis, Rebecka; Carlisle, Heidi; Clark, Chantry; Marin, Stephanie J; Moody, David E

    2012-03-01

    Patterns of buprenorphine and metabolites were examined in 1946 positive urine samples analyzed by liquid chromatography-tandem mass spectrometry for free (unconjugated) buprenorphine and norbuprenorphine (quantitative, 2 to 1000 ng/mL) and buprenorphine-glucuronide (B3G) and norbuprenorphine-glucuronide (N3G) (semi-quantitative, 5 to 1000 ng/mL). Two distribution patterns predominated with 49.1% positive for norbuprenorphine, B3G, and N3G and 41.6% positive for buprenorphine, norbuprenorphine, B3G, and N3G. Buprenorphine, positive in 45.5% of samples, was mostly < 5 ng/mL (median 6.1 ng/mL), but 9.8% were > 1000 ng/mL. Norbuprenorphine, B3G, and N3G had semi-Gaussian distributions with medians of 64.7, 108, and 432 ng/mL, respectively. With buprenorphine < 100 ng/mL (767 samples) or ≥ 100 ng/mL (19 quantifiable samples), the respective median metabolic ratios (free norbuprenorphine/free buprenorphine) were 25.0 and 0.15. In 12 retested "> 1000 ng/mL" buprenorphine samples, free buprenorphine was 4160 to 39,400 ng/mL and free naloxone 2140 to 9560 ng/mL. In 87 subsequent samples with buprenorphine < 20 ng/mL, naloxone concentrations were < 50 ng/mL. Concentrations of buprenorphine > 100 ng/mL (particularly with low metabolite concentrations) are suspect of urine adulteration with medication (4% in the database) that can be checked in most cases by concurrent analysis for naloxone. PMID:22337776

  16. Illicit Use of Buprenorphine in a Community Sample of Young Adult Non-Medical Users of Pharmaceutical Opioids

    PubMed Central

    Daniulaityte, Raminta; Falck, Russel; Carlson, Robert G.

    2011-01-01

    BACKGROUND There is growing evidence about illicit use of buprenorphine in the U.S. The study aims to: 1) identify prevalence and predictors of illicit buprenorphine use in a community sample of 396 young adult (18-23 years old) non-medical users of pharmaceutical opioids; 2) describe knowledge, attitudes and behaviors linked to illicit buprenorphine use as reported by a qualitative sub-sample (n=51). METHODS Participants were recruited using respondent-driven sampling. Qualitative interview participants were selected from the larger sample. The sample (n=396) was 54% male and 50% white; 7.8% reported lifetime illicit use of buprenorphine. RESULTS Logistic regression analysis results indicate that white ethnicity, intranasal inhalation of pharmaceutical opioids, symptoms of opioid dependence, and a greater number of pharmaceutical opioids used in lifetime were statistically significant predictors of illicit buprenorphine use. Qualitative interviews revealed that buprenorphine was more commonly used by more experienced users who were introduced to it by their “junkie friends.” Those who used buprenorphine to self-medicate withdrawal referred to it as a “miracle pill.” When used to get high, reported experiences ranged from “the best high ever” to “puking for days.” Participants reported using buprenorphine/naloxone orally or by intranasal inhalation. Injection of buprenorphine without naloxone was also reported. CONCLUSION Our findings suggest that illicit buprenorphine use is gaining ground primarily among whites and those who are more advanced in their drug use careers. Continued monitoring is needed to better understand evolving patterns and trends of illicit buprenorphine use. PMID:22036303

  17. Opioid partial agonist buprenorphine dampens responses to psychosocial stress in humans

    PubMed Central

    Bershad, Anya K.; Jaffe, Jerome H.; Childs, Emma; de Wit, Harriet

    2014-01-01

    Preclinical and clinical evidence indicates that opioid drugs have stress-dampening effects. In animal models, opioid analgesics attenuate responses to isolation distress, and in humans, opioids reduce stress related to anticipation of physical pain. The stress-reducing effects of opioid drugs may contribute to their abuse potential. Despite this evidence in laboratory animals, the effects of opioids on responses to psychosocial stress have not been determined in humans. Here we examined the effects of buprenorphine, a μ-opioid partial agonist used to treat opioid dependence and pain, on subjective and physiological responses to a stressful public speaking task in healthy adults. We hypothesized that buprenorphine would reduce subjective and physiological stress responses. Healthy adult volunteers (N = 48) were randomly assigned to receive placebo, 0.2mg sublingual buprenorphine, or 0.4mg sublingual buprenorphine in a two-session study with a stressful speaking task (Trier Social Stress Test; TSST) and a non-stressful control task. During the sessions, the participants reported on their mood states, provided subjective appraisals of the task, and measures of salivary cortisol, heart rate, and blood pressure at regular intervals. Stress produced its expected effects, increasing heart rate, blood pressure, salivary cortisol, and subjective ratings of anxiety and negative mood. In line with our hypothesis, both doses of buprenorphine significantly dampened salivary cortisol responses to stress. On self-report ratings, buprenorphine reduced how threatening participants found the tasks. These results suggest that enhanced opioid signaling dampens responses to social stress in humans, as it does in laboratory animals. This stress-dampening effect of buprenorphine may contribute to the non-medical use of opioid drugs. PMID:25544740

  18. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... which treat wastes subsequently discharged to a water of the United States pursuant to a permit issued under section 402 of the Clean Water Act (CWA), or which treat wastes in a CWA-equivalent treatment...) contaminated with an inorganic metal-bearing hazardous waste; (3) The waste, at point of generation,...

  19. Systematic review and meta-analysis of skin substitutes in the treatment of diabetic foot ulcers: Highlights of a Cochrane systematic review.

    PubMed

    Santema, T B Katrien; Poyck, Paul P C; Ubbink, Dirk T

    2016-07-01

    Skin substitutes are increasingly used in the treatment of various types of acute and chronic wounds. The aim of this study was to perform a systematic review and meta-analysis to evaluate the effectiveness of skin substitutes on ulcer healing and limb salvage in the treatment of diabetic foot ulcers. Randomized clinical trials were searched and assessed following the methodology of The Cochrane Collaboration. We included 17 trials, totaling 1655 randomized participants. Risk of bias was variable among included trials. Thirteen trials compared the skin substitutes with standard care. The pooled results showed that that skin substitutes can, in addition to standard care, increase the likelihood of achieving complete ulcer closure compared with standard care alone after 6-16 weeks (risk ratio 1.55, 95% confidence interval [CI] 1.30-1.85). Four of the included trials compared two types of skin substitutes but no particular product showed a superior effect over another. Two trials reported on total incidence of lower limb amputations. Pooling the results of these two trials yielded a statistically significantly lower amputation rate among patients treated with skin substitutes (risk ratio 0.43, 95% CI 0.23-0.81), although the absolute risk difference was small (-0.06, 95% CI -0.10 to -0.01). This systematic review provides evidence that skin substitutes can, in addition to standard care, increase the likelihood of achieving complete ulcer closure compared with standard care alone in the treatment of diabetic foot ulcers. However, effectiveness on the long term, including lower limb salvage and recurrence, is currently lacking and cost-effectiveness is unclear. PMID:27062201

  20. On drug treatment and social control: Russian narcology's great leap backwards

    PubMed Central

    Elovich, Richard; Drucker, Ernest

    2008-01-01

    The medical discipline of narcology in Russia is a subspecialty of psychiatry from the Soviet era and it is given warrant to define the scope of health activities with regard to alcohol and other drug use, drug users, and related problems. Narcological practice is in turn constrained by the State. The emergence of widespread injection opiate use and associated HIV morbidities and mortalities during the first decade following the collapse of the Soviet Union has brought the contradictions in Russian narcological discourse into high relief. Narcology officials in the Russian Federation have consistently opposed substitution treatment for opiate dependence – the replacement of a short-acting illegal substance with a longer acting prescribed drug with similar pharmacological action but lower degree of risk. Thus, despite the addition of methadone and buprenorphine to WHO's list of essential medicines in 2005 and multiple position papers by international experts calling for substitution treatment as a critical element in the response to HIV (IOM, 2006; UNODC, UNAIDS, and WHO, 2005), methadone or buprenorphine remain prohibited by law in Russia. The authors detail Russian opposition to the prescription of methadone and buprenorphine, describing four phenomena: (1) the dominance of law enforcement and drug control policy over public health and medical ethics ; (2) the conflation of Soviet era alcoholism treatment with treatment for opiate dependence; (3) the near universal representation of detoxification from drugs as treatment for dependence; and (4) a framework for judging treatment efficacy that is restricted to "cure" versus "failure to cure," and does not admit its poor outcomes or recognize alternative frameworks for gauging treatment of opiate dependence. In keeping with this position, Russian narcology officials have taken an implacable ideological stance toward illicit drug use, the people who use drugs, and their treatment. By adopting policies and practices

  1. Buprenorphine/Naloxone and Methadone Effects on Laboratory Indices of Liver Health: a Randomized Trial

    PubMed Central

    Saxon, Andrew J.; Ling, Walter; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Ang, Alfonso; Doraimani, Geetha; Tasissa, Gudaye; Lokhnygina, Yuliya; Leimberger, Jeff; Bruce, R. Douglas; McCarthy, John; Wiest, Katharina; McLaughlin, Paul; Bilangi, Richard; Cohen, Allan; Woody, George; Jacobs, Petra

    2012-01-01

    BACKGROUND Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants. METHODS This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met “evaluable” criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified. RESULTS Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants. CONCLUSIONS This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury. PMID:22921476

  2. Attitudes towards informed consent, confidentiality, and substitute treatment decisions in southern African medical students: a case study from Zimbabwe.

    PubMed

    Hipshman, L

    1999-08-01

    This study explored the attitudes of biomedical science students (medical students) in a non-Western setting towards three medical ethics concepts that are based on fundamental Western culture ethical principles. A dichotomous (agree/disagree) response questionnaire was constructed using Western ethnocentric culture (WEC) based perspectives of informed consent, confidentiality, and substitute decision-making. Hypothesized WEC-Biased responses were assigned to the questionnaire's questions or propositions. A number of useful responses (169) were obtained from a large, cross-sectional, convenience sample of the MBChB students at the University of Zimbabwe Medical School. Statistical analysis described the differences in response patterns between the student's responses compared to the hypothesized WEC-Biased response. The effect of the nine independent variables on selected dependent variables (responses to certain questionnaire questions) was analyzed by stepwise logistic regression. Students concurred with the hypothesized WEC-Biased responses for two-thirds of the questionnaire items. This agreement included support for the role of legal advocacy in the substitute decision-making process. The students disagreed with the hypothesized WEC-Biased responses in several important medical ethics aspects. Most notably, the students indicated that persons with mental dysfunctions, as a class, were properly considered incompetent to make treatment decisions. None of the studied independent variables was often associated with students' responses, but training year was more frequently implicated than either ethnicity or gender. In order to develop internationally and culturally relevant medical ethics standards, non-Western perspectives ought to be acknowledged and incorporated. Two main areas for further efforts include: curriculum development in ethics reasoning and related clinical (medico-legal) decision-making processes that would be relevant to medical students from

  3. Brief versus extended counseling along with buprenorphine/naloxone for HIV-infected opioid dependent patients.

    PubMed

    Tetrault, Jeanette M; Moore, Brent A; Barry, Declan T; O'Connor, Patrick G; Schottenfeld, Richard; Fiellin, David A; Fiellin, Lynn E

    2012-12-01

    Untreated opioid dependence adversely affects HIV outcomes. Integrating buprenorphine/naloxone into HIV treatment settings is feasible; however, the optimal level of counseling has not been established. We conducted a 12-week randomized clinical trial of physician management (PM) versus PM plus enhanced medical management (EMM) in 47 subjects. At 12 weeks, there were no differences between the two groups in percentage of opioid negative urines (63.6% PM vs. 69.0% PM+EMM, p=.5), maximum duration of continuous abstinence (4.9 weeks PM vs. 5.2 weeks PM+EMM, p=.8) or retention (80% PM vs. 59% PM+EMM, p=.1). The percentage of subjects with detectable HIV viral loads decreased from 58% at baseline to 40% at 12 weeks across both groups (p=.02 for time) with no between group differences (p=.84 and p=.27 for the interaction). Providing more extensive counseling beyond PM is feasible in an HIV clinic, but we are unable to detect an improvement in outcomes associated with these services. PMID:22938914

  4. Stability of buprenorphine, haloperidol and glycopyrrolate mixture in a 0.9% sodium chloride solution.

    PubMed

    Jäppinen, A; Kokki, H; Naaranlahti, T J; Rasi, A S

    1999-12-01

    Combinations of opioids and adjuvant drug solutions are often used in clinical practice while little information is available on their microbiological or chemical stability. Currently there are no commercially available, prepacked, ready-to-use epidural or subcutaneous mixtures. Thus, epidural and subcutaneous analgesic mixtures must be prepared in the pharmacy on an as-needed basis. Such mixtures are typically used for the treatment of severe pain in cancer patients. The aim of this study was to investigate the microbiological and chemical stability of a buprenorphine, haloperidol and glycopyrrolate mixture in a 0.9% sodium chloride solution. A high performance liquid chromatographic (HPLC) method and pH-meter were used to conduct the analyses. Antimicrobial activity of each component was studied by an agar dilution method. According to the results from the chemical and microbiological stability studies, this mixture can be stored in polypropylene (PP) syringes and polyvinyl chloride (PVC) medication cassettes for at least 30 days at either 21 degrees C or 4 degrees C, and for 16 days in PP syringes at 36 degrees C, and for 9 days in PVC medication cassettes at 36 degrees C. PMID:10658237

  5. Relationship between buprenorphine adherence and health service utilization and costs among opioid dependent patients.

    PubMed

    Tkacz, Joseph; Volpicelli, Joseph; Un, Hyong; Ruetsch, Charles

    2014-04-01

    Buprenorphine-medication assisted therapy (B-MAT) is an effective treatment for opioid dependence, but may be considered cost-prohibitive based on ingredient cost alone. The purpose of this study was to use medical and pharmacy claims data to estimate the healthcare service utilization and costs associated with B-MAT adherence among a sample of opioid dependent members. Members were placed into two adherence groups based on 1-year medication possession ratio (≥ 0.80 vs. <0.80). The B-MAT adherent group incurred significantly higher pharmacy charges (adjusted means; $6,156 vs. $3,581), but lower outpatient ($9,288 vs. $14,570), inpatient ($10,982 vs. $26,470), ER ($1,891 vs. $4,439), and total healthcare charges ($28,458 vs. $49,051; p<0.01) compared to non-adherent members. Adherence effects were confirmed in general linear models. Though B-MAT adherence requires increased pharmacy utilization, adherent individuals were shown to use fewer expensive health care services, resulting in overall reduced healthcare expenditure compared to non-adherent patients. PMID:24332511

  6. An in vitro approach to estimate putative inhibition of buprenorphine and norbuprenorphine glucuronidation.

    PubMed

    Oechsler, Stephanie; Skopp, Gisela

    2010-05-01

    An in vitro inhibition study was performed to investigate potential drug-drug interactions on glucuronidation of buprenorphine (BUP) and norbuprenorphine (NBUP), which represents the major elimination pathway of the drug using cDNA-expressed uridine 5'-diphosphate glucuronosyltransferases (UGTs) and human liver microsomes (HLMs). Following identification of major UGT enzymes for BUP and NBUP glucuronidation, substrates were incubated with drugs (amitriptyline, nortriptyline, lamotrigine, oxazepam, and temazepam), which are extensively cleared by glucuronidation as well as are often used during maintenance treatment. To evaluate the inhibitory potential, the half maximal inhibitor concentration (IC(50)), the inhibition constant (K (i)), and the inhibitor concentration (K (I)) that yield half the maximum rate of inactivation and the enzyme inactivation rate constant (k (inact)) were determined, if appropriate. Amitriptyline and temazepam are inhibitors of NBUP glucuronidation (UGT1A3, HLMs), whereas BUP glucuronidation was affected by amitriptyline (HLMs), oxazepam, and temazepam (UGT2B7). Additionally, BUP inhibits NBUP glucuronidation (UGT1A1, 1A3, HLMs) and vice versa (UGT1A3). A decrease in the metabolic clearance of NBUP may increase the risk of adverse effects such as respiratory depression. Further investigations are needed to evaluate whether inhibition of BUP and NBUP glucuronidation contributes to adverse events. PMID:20111869

  7. Drug interactions associated with methadone, buprenorphine, cocaine, and HIV medications: implications for pregnant women

    PubMed Central

    McCance-Katz, Elinore F.

    2010-01-01

    Pregnancy in substance-abusing women with HIV/AIDS presents a complex clinical challenge. Opioid-dependent women need treatment with opioid therapy during pregnancy to protect the health of mother and developing fetus. However, opioid therapies, methadone and buprenorphine, may have drug interactions with some HIV medications that can have adverse effects leading to suboptimal clinical outcomes. Further, many opioid-dependent individuals have problems with other forms of substance abuse, for example, cocaine abuse, that could also contribute to poor clinical outcomes in a pregnant woman. Physiological changes, including increased plasma volume and increased hepatic and renal blood flow, occur in the pregnant woman as the pregnancy progresses and may alter medication needs with the potential to exacerbate drug interactions, although there is sparse literature on this issue. Knowledge of possible drug interactions between opioids, other abused substances such as cocaine, HIV therapeutics, and other frequently required medications such as antibiotics and anticonvulsants is important to assuring the best possible outcomes in the pregnant woman with opioid dependence and HIV/AIDS. PMID:20965297

  8. Toxicological and pathological findings in a series of buprenorphine related deaths. Possible risk factors for fatal outcome.

    PubMed

    Seldén, Tor; Ahlner, Johan; Druid, Henrik; Kronstrand, Robert

    2012-07-10

    Buprenorphine is considered to have little respiratory side effects at therapeutic doses and the partial agonistic properties should produce a "ceiling effect" for respiratory depression at higher doses. Still, there are several reports on buprenorphine related deaths. Most deaths involve drug users and the co-administration of other CNS depressant drugs as well as reduced tolerance have been suggested to be risk factors. The primary aims were to investigate if lack of tolerance and/or co-ingestion of other psychotropic drugs are significant risk factors in buprenorphine fatalities. From July 2005 to September 2009, all autopsy cases where buprenorphine or norbuprenorphine had been detected in femoral blood and where analysis of buprenorphine had been performed in urine were selected. Results from the postmortem examination and toxicology were compiled. Postmortem toxicology was performed using the routine methodology at the laboratory. In total, 97 subjects were included in the study. These were divided into four groups; Intoxication with buprenorphine (N=41), Possible intoxication with buprenorphine (N=24), Control cases where buprenorphine was not the cause of death (N=14), and Unclear (N=18). The metabolite to parent compound ratios in both blood and urine in the Intoxication group were significantly different from those in the Control and Unclear groups. An extensive poly-drug use was seen in all groups with several additional opioids in the Possible group (54%) and in the Unclear group (78%) and hypnotics or sedatives in more than 75% of the Intoxication, Possible, and Unclear cases. Illicit drugs were present in all groups but not to a great extent with amphetamine and tetrahydrocannabinol as the main findings. Interestingly, 4 cases in the Intoxication group presented with no other significant drugs in blood other than buprenorphine. We conclude that a lethal concentration of buprenorphine in blood cannot be defined. Instead the analysis of blood as well as

  9. Challenges to Implementing Opioid Substitution Therapy in Ukrainian Prisons: Personnel Attitudes Toward Addiction, Treatment, and People With HIV/AIDS

    PubMed Central

    Polonsky, Maxim; Azbel, Lyuba; Wickersham, Jeffrey A.; Taxman, Faye S.; Grishaev, Evgeny; Dvoryak, Sergey; Altice, Frederick L.

    2015-01-01

    Background Ukraine is experiencing one of the most volatile HIV epidemics globally, fueled primarily by people who inject drugs (PWIDs), and a parallel incarceration epidemic. Opioid substitution therapy (OST) is internationally recognized as one of the most effective forms of treatment for opioid dependence and is among the most effective HIV prevention strategies available, yet efforts to adopt it in Ukraine’s Criminal Justice System (CJS) have been thwarted. Methods To understand the reluctance of the Ukrainian CJS to adopt OST despite the overwhelming evidence pointing to its health benefits and improved criminal justice outcomes, we conducted the first survey of Ukrainian prison administrative, medical and custodial staff (N=243) attitudes towards addiction in general, OST, and people living with HIV/AIDS (PLWHA) in representative regions of Ukraine. Results Results revealed that Ukrainian CJS workers’ attitudes toward OST, PLWHA, and drug addiction were universally negative, but differed substantially along geographic and occupational lines. Whereas geographic and cultural proximity to the European Union drove positive attitudes in the west, in the southern region we observed an identifiability effect, as workers who worked directly with prisoners held the most positive attitudes. We also found that knowledge mediated the effect of drug intolerance on OST attitudes. Conclusion In Ukraine, adoption of OST is more influenced by ideological biases and prejudices than by existing scientific evidence. By elucidating existing attitudes among CJS personnel, this assessment will help direct subsequent interventions to address the barriers to implementing evidence-based HIV prevention treatments. PMID:25620732

  10. [Transitory bone loss during substitution treatment for hypothyroidism. Results of a two year prospective study].

    PubMed

    Trémollières, F; Pouillès, J M; Louvet, J P; Ribot, C

    1991-12-01

    The authors report the results of a prospective study designed to assess changes in vertebral and femoral bone density during the first two years of replacement therapy in 10 patients with hypothyroidism (4 men, 6 women). During the first year, bone density measured by dual photon absorptiometry fell significantly in the lumbar vertebrae (-5.4%), neck of the femur (-7%) and the trochanteric region (-7.3%). This bone loss was accompanied by an early increase in serum osteocalcin levels, urinary calcium/urinary creatinine ratio and in Sex Hormone Binding Globulin. During the second year, there was complete recovery of values of vertebral and trochanteric bone density, while density of the neck of the femur remained significantly lower than initial values. None of the patients showed any evidence of overdose during the period of monitoring of clinical and laboratory (free T4, total and free T3, ultra-sensitive TSH) parameters. This transitory bone loss could be indicative of a state of tissue hyperthyroidism and/or "hypersensitivity" of hypothyroid bone to the action of thyroid hormones. Its influence on the subsequent risk of fracture remains unclear. In the current state of knowledge, measurement of vertebral and femoral bone density appears to be indicated in patients given long term treatment which suppresses TSH, or requiring replacement therapy for severe hypothyroidism. Any demineralisation prior to treatment could justify the temporary prescription of an antiosteoclastic agent. PMID:1780668

  11. Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus)

    PubMed Central

    Taylor, Bryan F; Ramirez, Harvey E; Battles, August H; Andrutis, Karl A; Neubert, John K

    2016-01-01

    Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose–response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male rats receiving buprenorphine mixed in nut paste, a significant analgesic response was observed at 0.5 and 0.6 mg/kg. None of the doses tested produced a significant analgesic response in female rats. Our results indicate that at the doses tested, tramadol and buprenorphine produced an analgesic response in male rats. In female rats, tramadol shows a higher analgesic effect than buprenorphine. The analgesic effects observed 60 min after administration of the statistically significant oral doses of both drugs were similar to the analgesic effects of 0.03 mg/kg subcutaneous buprenorphine 30 min after administration. The method of voluntary ingestion could be effective, is easy to use, and would minimize stress to the rats during the immediate postoperative period. PMID:26817983

  12. The unique role of transdermal buprenorphine in the global chronic pain epidemic.

    PubMed

    Pergolizzi, Joseph V; Scholten, Willem; Smith, Kevin J; Leighton-Scott, James; Willis, Jenna C; Henningfield, Jack E

    2015-06-01

    Pain is a global epidemic, exacerbated by barriers to access of opioid analgesics. Regulations about opioids attempt to protect public health from the risks of harmful use of opioids, diversion, and dependence. Transdermal buprenorphine is an effective opioid analgesic agent with unique properties that may make it particularly well suited for more widespread use. It is a versatile analgesic product with demonstrated safety and effectiveness in cancer and noncancer pain populations. Its pharmacological properties make it a first-line opioid analgesic for geriatric patients and patients with renal dysfunction; no dosing adjustments need to be made. The 7-day transdermal delivery system is convenient for patients and promotes compliance. A low dose of buprenorphine can provide effective and well-tolerated pain relief. Although buprenorphine has been associated with certain opioid-related adverse effects, such as dizziness and nausea, it is associated with a lower rate of constipation than many other opioid analgesics. The potential for nonmedical use of buprenorphine is relatively low compared with other opioid agents. Buprenorphine has a relatively low likeability for nonmedical use and the transdermal matrix patch renders the substance particularly difficult to extract for illicit purposes. PMID:26205326

  13. Pharmacokinetics of a single subcutaneous dose of sustained release buprenorphine in northern elephant seals (Mirounga angustirostris).

    PubMed

    Molter, Christine M; Barbosa, Lorraine; Johnson, Shawn; Knych, Heather K; Chinnadurai, Sathya K; Wack, Raymund F

    2015-03-01

    Information regarding analgesics in pinnipeds is limited. This study aimed to establish the pharmacokinetic parameters of a single subcutaneous dose of sustained release buprenorphine (Buprenorphine SR) in juvenile northern elephant seals (Mirounga angustirostris) with regard to its potential to provide long-lasting analgesia that requires infrequent dosing. Seals (n=26) were administered a single dose of sustained release buprenorphine at 0.12 mg/kg s.c. Blood samples were collected from the extradural intervertebral vein at 0 hr and at three or four of the following time points: 0.5, 1, 2, 6, 12, 24, 36, 48, 60, 96, 120, and 144 hr. Seals were examined daily for systemic and local adverse reactions. Plasma was analyzed by liquid chromatography tandem-mass spectrometry for buprenorphine and norbuprenorphine concentrations. A noncompartmental analysis for pharmacokinetic parameters was calculated using standard methods and equations. An average maximum concentration of 1.21 ng/ml (0.3-2.9 ng/ml) was detected 12 hr postadministration. Concentrations were quantifiable up to 144 hr postadministration but were below those expected to provide analgesia in some other species. No systemic adverse effects were noted in healthy seals receiving sustained release buprenorphine. Cellulitis or abscesses at the injection site were observed in 6/26 (23%) seals between 24 and 168 hr postadministration. Adverse local effects suggest that this drug should be used with caution in northern elephant seals. PMID:25831576

  14. UHPLC-MS/MS quantification of buprenorphine, norbuprenorphine, methadone, and glucuronide conjugates in umbilical cord plasma.

    PubMed

    Kyle, Amy Redmond; Carmical, Jennifer; Shah, Darshan; Pryor, Jason; Brown, Stacy

    2015-10-01

    Opioid use during pregnancy can result in the newborn being physically dependent on the substance, thus experiencing drug withdrawal, termed neonatal abstinence syndrome (NAS). Buprenorphine and methadone are two drugs used to treat opioid withdrawal and are approved for use in pregnancy. Quantification of these compounds in umbilical cord plasma would help assess in utero exposure of neonates in cases of buprenorphine or methadone use during pregnancy. An LC-MS/MS method using solid-phase extraction sample preparation was developed and validated for the simultaneous quantification of methadone, buprenorphine, norbuprenorphine, and glucuronide metabolites in umbilical cord plasma. The average accuracy (percentage error) and precision (relative standard deviation) were <15% for each validated concentration. Our data establishes a 2 week maximum freezer storage window in order to achieve the most accurate cord plasma concentrations of these analytes. Additionally, we found that the umbilical cord tissue analysis was less sensitive compared with analysis with umbilical cord blood plasma, indicating that this may be a more appropriate matrix for determination of buprenorphine and metabolite concentrations. This method was successfully applied to the analysis of cord blood from women with known buprenorphine or methadone use during pregnancy. PMID:25808363

  15. Reduced fear-recognition sensitivity following acute buprenorphine administration in healthy volunteers.

    PubMed

    Ipser, Jonathan C; Terburg, David; Syal, Supriya; Phillips, Nicole; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Thomas, Kevin; Stein, Dan J; van Honk, Jack

    2013-01-01

    In rodents, the endogenous opioid system has been implicated in emotion regulation, and in the reduction of fear in particular. In humans, while there is evidence that the opioid antagonist naloxone acutely enhances the acquisition of conditioned fear, there are no corresponding data on the effect of opioid agonists in moderating responses to fear. We investigated whether a single 0.2mg administration of the mu-opioid agonist buprenorphine would decrease fear sensitivity with an emotion-recognition paradigm. Healthy human subjects participated in a randomized placebo-controlled within-subject design, in which they performed a dynamic emotion recognition task 120min after administration of buprenorphine and placebo. In the recognition task, basic emotional expressions were morphed between their full expression and neutral in 2% steps, and presented as dynamic video-clips with final frames of different emotional intensity for each trial, which allows for a fine-grained measurement of emotion sensitivity. Additionally, visual analog scales were used to investigate acute effects of buprenorphine on mood. Compared to placebo, buprenorphine resulted in a significant reduction in the sensitivity for recognizing fearful facial expressions exclusively. Our data demonstrate, for the first time in humans, that acute up-regulation of the opioid system reduces fear recognition sensitivity. Moreover, the absence of an effect of buprenorphine on mood provides evidence of a direct influence of opioids upon the core fear system in the human brain. PMID:22651957

  16. Postoperative pain relief with epidural buprenorphine versus epidural butorphanol in laparoscopic hysterectomies: A comparative study

    PubMed Central

    Jose, Dona Elsa; Ganapathi, P.; Anish Sharma, N. G.; Shankaranarayana, P.; Aiyappa, D. S.; Nazim, Mohammed

    2016-01-01

    Background: The purpose of this study was to compare the safety and efficacy of postoperative analgesia with epidural buprenorphine and butorphanol tartrate. Methods: Sixty patients who were scheduled for elective laparoscopic hysterectomies were randomly enrolled in the study. At the end of the surgery, in study Group A 1 ml (0.3 mg) of buprenorphine and in Group B 1 ml (1 mg) of butorphanol tartrate both diluted to 10 ml with normal saline was injected through the epidural catheter. Visual analog pain scales (VAPSs) were assessed every hour till the 6th h, then 2nd hourly till the 12th h. To assess sedation, Ramsay sedation score was used. The total duration of postoperative analgesia was taken as the period from the time of giving epidural drug until the patients first complain of pain and the VAPS is more than 6. Patients were observed for any side effects such as respiratory depression, nausea, vomiting, hypotension, bradycardia, pruritus, and headache. Results: Buprenorphine had a longer duration of analgesia when compared to butorphanol tartrate (586.17 ± 73.64 vs. 342.53 ± 47.42 [P < 0.001]). Nausea, vomiting (13% vs. 10%), and headache (20% vs. 13%) were more in buprenorphine group; however, sedation score and pruritus (3% vs. 6%) were found to be more with butorphanol. Conclusion: Epidural buprenorphine significantly reduced pain and increased the quality of analgesia with a longer duration of action and was a better alternative to butorphanol for postoperative pain relief. PMID:26957696

  17. Opioid receptor imaging and displacement studies with [6-O-[11C] methyl]buprenorphine in baboon brain.

    PubMed

    Galynker, I; Schlyer, D J; Dewey, S L; Fowler, J S; Logan, J; Gatley, S J; MacGregor, R R; Ferrieri, R A; Holland, M J; Brodie, J; Simon, E; Wolf, A P

    1996-04-01

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[11C]methyl]buprenorphine ([11C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% +/- 2.2% and 43% +/- 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [11C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (< 15%) effects on cerebellum. Naloxone treatment significantly reduced the slope of the Patlak plot in receptor-containing regions. These results demonstrate that [11C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi. PMID:8782244

  18. Combined effects of post-growth thermal treatment and chemical substitution on physical properties of CaFe2As2

    SciTech Connect

    Ran, Sheng

    2014-12-01

    This thesis summarizes experimental work using process of postgrowth thermal treatment and chemical substitution as tuning parameters in the study of physical properties of CaFe2As2. Details of sample preparation and characterization are given as well as various phase diagrams.

  19. Clinical Efficacy of Sustained-Release Buprenorphine with Meloxicam for Postoperative Analgesia in Beagle Dogs Undergoing Ovariohysterectomy

    PubMed Central

    Nunamaker, Elizabeth A; Stolarik, DeAnne F; Ma, Junli; Wilsey, Amanda S; Jenkins, Gary J; Medina, Chris L

    2014-01-01

    The goal of the current study was to compare the efficacy, adverse effects, and plasma buprenorphine concentrations of sustained-release buprenorphine (SRB) and buprenorphine after subcutaneous administration in dogs undergoing ovariohysterectomy. In a prospective, randomized, blinded design, 20 healthy adult female Beagle dogs underwent routine ovariohysterectomy and received multimodal analgesia consisting of meloxicam and one of two buprenorphine formulations. Dogs were randomly assigned to receive either SRB (0.2 mg/kg SC, once) or buprenorphine (0.02 mg/kg SC every 12 h for 3 d). Blinded observers assessed all dogs by using sedation scores, pain scores, temperature, HR, RR, and general wellbeing. Dogs were provided rescue analgesia with 0.02 mg/kg buprenorphine SC if the postoperative pain score exceeded a predetermined threshold. Blood samples were collected, and mass spectrometry was used to determine plasma buprenorphine concentrations. Data were analyzed with a linear mixed model and Tukey–Kramer multiple comparison. Age, body weight, anesthetic duration, surgical duration, sevoflurane concentration, and cardiorespiratory variables did not differ significantly between groups. Dogs in both formulation groups had comparable postoperative sedation and pain scores. One dog from each formulation group had breakthrough pain requiring rescue analgesia. Plasma buprenorphine concentrations remained above a hypothesized therapeutic concentration of 0.6 ng/mL for 136.0 ± 11.3 and 10.67 ± 0.84 h for SRB and buprenorphine, respectively. Based on the results of this study, multimodal analgesic regimens consisting of meloxicam and either buprenorphine or SRB are equally efficacious in managing pain associated with an ovariohysterectomy and show comparable side effects. PMID:25255072

  20. Development of nanofibrous cellulose acetate/gelatin skin substitutes for variety wound treatment applications.

    PubMed

    Vatankhah, Elham; Prabhakaran, Molamma P; Jin, Guorui; Mobarakeh, Laleh Ghasemi; Ramakrishna, Seeram

    2014-02-01

    The major component of fibrous extracellular matrix of dermis is composed of a complex combination of proteins and polysaccharides. Electrospun cellulose acetate/gelatin might be an effective simulator of the structure and composition of native skin and during this study, we electrospun cellulose acetate/gelatin membranes in various compositions and their performance as a scaffold for either skin tissue engineering or as a wound dressing was evaluated. Skin treatment products, whether tissue-engineered scaffolds or wound dressings, should be sufficiently hydrophilic to allow for gas and fluid exchange and absorb excess exudates while controlling the fluid loss. However, a wound dressing should be easily removable without causing tissue damage and a tissue-engineered scaffold should be able to adhere to the wound, and support cell proliferation during skin regeneration. We showed that these distinct adherency features are feasible just by changing the composition of cellulose acetate and gelatin in composite cellulose acetate/gelatin scaffolds. High proliferation of human dermal fibroblasts on electrospun cellulose acetate/gelatin 25:75 confirmed the capability of cellulose acetate/gelatin 25:75 nanofibers as a tissue-engineered scaffold, while the electrospun cellulose acetate/gelatin 75:25 can be a potential low-adherent wound dressing. PMID:23640859

  1. Use of an Acetyl Derivative to Improve GC-MS Determination of Norbuprenorphine in the Presence of High Concentrations of Buprenorphine in Urine.

    PubMed

    Gervais, Joel R; Hobbs, Gregory A

    2016-04-01

    Certain patients being treated with Suboxone™ or Subutex™ can exhibit very high buprenorphine and low norbuprenorphine concentrations in urine. Very high buprenorphine can interfere with buprenorphine-D4 used as an internal standard, causing errors in norbuprenorphine determination by gas chromatography-mass spectrometry (GC-MS). We used a modified method of Wu et al. to introduce norbuprenorphine-D3 as a separate internal standard for norbuprenorphine. This allowed us to accurately measure norbuprenorphine in neat urine specimens when buprenorphine is present in extremely high concentrations. Laboratories measuring buprenorphine and metabolite by GC-MS may face this problem if their clientele includes patients being treated with other medications that interfere with the cytochrome p450 CYP 3A4-mediated conversion of buprenorphine to norbuprenorphine. PMID:26811236

  2. Effects of Buprenorphine on Behavioral Tests for Antidepressant and Anxiolytic Drugs in Mice

    PubMed Central

    Falcon, Edgardo; Maier, Kaitlyn; Robinson, Shivon A.; Hill-Smith, Tiffany E.; Lucki, Irwin

    2014-01-01

    Rationale Buprenorphine (BPN) has been shown to rapidly improve mood in treatment-resistant depressed patients in small clinical studies. However, BPN’s effects in preclinical tests for mood and antidepressant efficacy are largely unexplored. Objective The current study examined the effects of BPN in the forced swim test (FST) and novelty-induced hypophagia (NIH) test as measures of antidepressant and anxiolytic-like effects in C57BL/6J mice. Microdialysis was used to measure whether BPN engaged KORs in the nucleus accumbens shell (NAcSh) at a behaviorally active dose (0.25 mg/kg). Methods BPN was tested in the FST at both 30 min and 24 h post administration. Also measured in the FST at 24 h post administration were the KOR antagonist norbinaltorphimine (nor-BNI), the MOR agonist morphine and the reference antidepressant desipramine. The anxiolytic effects of BPN were examined in the NIH test 24 h after treatment. The effects of acute injection of BPN and the KOR agonist U50,488 were measured on extracellular DA levels in the NAcSh. Results BPN produced significant reductions in FST immobility without changing locomotor activity and reduced approach latencies in the novel environment of the NIH test when tested 24 h after treatment. Repeated daily BPN injections for 6 d did not produce tolerance to these behavioral effects. nor-BNI produced a similar antidepressant-like response in the FST 24 h postinjection but morphine and desipramine were ineffective. BPN (0.25 mg/kg) did not alter DA levels when given alone but prevented the KOR agonist U50,488 from reducing DA levels. Conclusions Acute and subchronic treatment with BPN produced antidepressant and anxiolytic-like responses in mice at doses that engage KORs. These studies support the clinical evidence that BPN may be a novel rapid-acting antidepressant medication and provides rodent models for investigating associated neurochemical mechanisms. PMID:25178815

  3. Vitreous Substitutes.

    PubMed

    Foster, William Joseph

    2008-04-01

    Modern vitreoretinal surgery is a young science. While tremendous developments have occurred in instrument design and technique since Machemer first described vitrectomy surgery in 1973[1], the application of advanced materials concepts to the development of intra-ocular compounds is a particularly exciting area of research. To date, the development of vitreous substitutes has played a significant role in enabling the dramatic and progressive improvement in surgical outcome, but perhaps no other area of research has the potential to further improve the treatment of retinal detachment and other retinal disorders. While prior research has focused solely upon the ability of a compound to re-attach the retina, future research should seek to enable the surgeon to inhibit the development of proliferative vitreoretinopathy and re-detachment, the integration of stem-cell therapies with surgical retina, long-term delivery of medications to the posterior segment, and the promotion of more rapid and complete visual rehabilitation. PMID:19343097

  4. Post-operative Analgesia in Opioid Dependent Patients: Comparison of Intravenous Morphine and Sublingual Buprenorphine

    PubMed Central

    Alizadeh, Shaabanali; Mahmoudi, Ghafar Ali; Solhi, Hassan; Sadeghi-Sedeh, Bahman; Behzadi, Reza; Kazemifar, Amir Mohammad

    2015-01-01

    Background Acute and chronic pain is prevalent in patients with opioid dependence. Lack of knowledge concerning the complex relationship between pain, opioid use, and withdrawal syndrome can account for the barriers encountered for pain management. This study was designed to evaluate the efficacy of sublingual (SL) buprenorphine for post-operative analgesia, compared with intravenous (IV) morphine. Methods A total of 68 patients, aged 20-60 years were randomly selected from whom had been underwent laparotomy due to acute abdomen in a University Teaching Hospital in Arak, Iran, and were also opioid (opium or heroin) abuser according to their history. After end of the surgery and patients’ arousal, the patients were evaluated for abdominal pain and withdrawal syndrome by visual analog scale (VAS) and clinical opioid withdrawal score (COWS), respectively 1, 6, and 24 h after the surgery. They received either morphine 5 mg IV or buprenorphine 2 mg SL, 1 h after end of the surgery, and then every 6 h for 24 h. Findings VAS was 4.47 ± 0.73 and 2.67 ± 0.53 at h 6 and 24 in buprenorphine group, respectively. The corresponding score was 5.88 ± 0.69 and 4.59 ± 0.74 in morphine group. At the same time, patients in buprenorphine experienced less severe withdrawal syndrome. Conclusion The present study confirmed the efficacy of SL buprenorphine as a non-invasive, but effective method for management of post-operative pain in opioid dependent patients. Result of this study showed that physicians can rely on SL buprenorphine for post-operative analgesia. PMID:26322212

  5. Pharmacokinetics of Sustained-Release and Transdermal Buprenorphine in Göttingen Minipigs (Sus scrofa domestica)

    PubMed Central

    Thiede, Allison J; Garcia, Kelly D; Stolarik, DeAnne F; Ma, Junli; Jenkins, Gary J; Nunamaker, Elizabeth A

    2014-01-01

    The opioid buprenorphine has been shown to provide adequate postoperative analgesia in both companion and laboratory animals. However, its use is still hindered by the need for multiple parenteral injections to achieve continuous analgesia. The purpose of the current study was to conduct a pharmacokinetic analysis of 2 new long-acting formulations of buprenorphine—an injectable sustained-release buprenorphine (SRB) and a transdermal buprenorphine (TDB) patch—in healthy Göttingen minipigs by using liquid chromatography–electrospray ionization–tandem mass spectrometry. Administration of 0.18 mg/kg SC SRB and 30 μg/h TDB achieved AUC0-Tlast of 221.6 ± 26.8 and 25.2 ± 3.9 ng × h/mL, respectively, compared with 9.7 ± 1.4 ng*h/mL for 0.02 mg/kg IV buprenorphine. By using a hypothesized therapeutic plasma buprenorphine concentration threshold of 0.1 ng/mL, therapeutic concentrations were achieved at the first study time point (5 to 30 min) and lasted an average of 8.0 ± 1.3 h for intravenous buprenorphine and 264.0 ± 32.2 h for SRB. TDB achieved therapeutic concentrations in 12 to 24 h after patch application, which lasted until the patch was removed at 72 h. The results of this study suggest that SRB and TDB are long-acting alternatives for pain management, and their use could decrease animal handling and stress, thereby simplifying pain management and improving welfare in laboratory swine. PMID:25650977

  6. Rapid quantification of buprenorphine-glucuronide and norbuprenorphine-glucuronide in human urine by LC-MS-MS.

    PubMed

    Hegstad, S; Khiabani, H Z; Øiestad, E L; Berg, T; Christophersen, A S

    2007-05-01

    A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the determination of buprenorphine-glucuronide (BUP-G) and norbuprenorphine-glucuronide (NBUP-G) in human urine. The method included a dilution step followed by filtration through a Mini-Uniprep Filter and direct injection onto the LC column. The analytes were quantified in multiple reactions monitoring mode using one transition ion. Norbuprenorpine-d(3) (NBUP-d(3)) was used as the internal standard. The concentration ranges were 6-161 ng/mL for BUP-G and 12-295 ng/mL for NBUP-G. Recoveries determined after filtration for the analytes were 75%. The between-day precision of the method was in the range of 4.8-11%. The limits of quantification were found to be 4.6 ng/mL for BUP-G and 11.8 ng/mL for NBUP-G. Approximately 1000 samples from law enforcement, prison inmates, probation services, and hospitals were analyzed by the presented method. The ratios of drug glucuronides versus creatinine were calculated for a selection of samples (n = 151), where there was information on treatment with buprenorphine between 16 and 20 mg/day. The majority (86%) of the samples had a ratio of BUP-G/creatinine below 570 microg/g, and 76% of the samples had NBUP-G/creatinine lower than 1060 microg/g. The LC-MS-MS method proved to be robust and specific for the determination of BUP-G and NBUP-G in urine. PMID:17555645

  7. Sublingual Buprenorphine/Naloxone for Chronic Pain in At-Risk Patients: Development and Pilot Test of a Clinical Protocol

    PubMed Central

    Rosenblum, Andrew; Cruciani, Ricardo A.; Strain, Eric C; Cleland, Charles M.; Joseph, Herman; Magura, Stephen; Marsch, Lisa A; McNicholas, Laura F; Savage, Seddon R; Sundaram, Arun; Portenoy, Russell K.

    2013-01-01

    Objective Sublingual buprenorphine/naloxone (Bup/Nx) is approved for addiction treatment and may be useful for pain management, particularly in opioid-treated pain patients with nonadherence behaviors. The transition of opioid-treated pain patients to buprenorphine carries the risk of precipitated withdrawal and increased pain. This study convened pain and addiction specialists to develop and pilot a clinical protocol for safe transitioning to Bup/Nx. Design The protocol was revised three times based on outside expert review and pilot study observations. The pilot was conducted with a prospective cohort of 12 patients with moderate to severe chronic pain, who were receiving long-term opioid therapy with any full μ-agonist drug, and had exhibited one or more aberrant drug-related behaviors. Patients were followed up for 3 to 6 months with the expectation that they would experience few adverse events and report lower pain severity. Results The three patients on the highest baseline opioid dose (equivalent to 303–450 mg of oral morphine) and the three on the lowest doses (≤20 mg) had early adverse events (AEs) when switched to Bup/Nx and did not complete the trial. Of the remaining six, one withdrew due to AEs; one responded well, then withdrew; and four completed a three-month trial. A mixed effects model controlling for dropouts found that average and worst pain significantly decreased after the switch to Bup/Nx (both p < .01). Conclusion Based on this experience, the protocol recommends Bup/Nx for pain only when baseline opioid doses are within bounds that reduce AEs at transition and incorporates dose flexibility to further reduce risks. This protocol warrants further testing. PMID:23264315

  8. Neonatal Abstinence Syndrome: Presentation and Treatment Considerations.

    PubMed

    Jones, Hendrée E; Kaltenbach, Karol; Johnson, Elisabeth; Seashore, Carl; Freeman, Emily; Malloy, Erin

    2016-01-01

    This clinical case conference discusses the treatment of a pregnant woman with opioid use disorder in a comprehensive care program that includes buprenorphine pharmacotherapy. The presentation summarizes common experiences that pregnant women who receive buprenorphine pharmacotherapy face, and also what their prenatally opioid-exposed children confront in the immediate postpartum period. It describes the elements of a successful comprehensive care model and corollary neonatal abstinence syndrome treatment regimen. Expert commentary is included on issues that arise in the buprenorphine induction and maintenance throughout the prenatal and postpartum periods and in the treatment of co-occurring mental health problems during both the prenatal and postpartum periods, particularly the treatment of depression. There is also expert commentary on the care of opioid-exposed neonates, with attention to the treatment for neonatal abstinence syndrome. PMID:27244045

  9. Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: a very low dose naltrexone and buprenorphine open label trial

    PubMed Central

    Mannelli, Paolo; Wu, Li-Tzy; Peindl, Kathleen S.; Swartz, Marvin S.; Woody, George E.

    2014-01-01

    BACKGROUND The approval of extended release injectable naltrexone (XR-NTX; Vivitrol®) has introduced a new option for treating opioid addiction, but studies are needed to identify its place within the spectrum of available therapies. The absence of physiological opioid dependence is a necessary and challenging first step for starting XR-NTX. Outpatient detoxification gives poor results and inpatient detoxification is either unavailable or too brief for the physiological effects of opioids to resolve. Here we present findings from an open label study that tested whether the transition from opioid addiction to XR-NTX can be safely and effectively performed in an outpatient setting using very low dose naltrexone and buprenorphine. METHODS Twenty treatment seeking opioid addicted individuals were given increasing doses of naltrexone starting at 0.25 mg with decreasing doses of buprenorphine starting at 4 mg during a 7-day outpatient XR-NTX induction procedure. Withdrawal discomfort, craving, drug use, and adverse events were assessed daily until the XR-NTX injection, then weekly over the next month. RESULTS Fourteen of the 20 participants received XR-NTX and 13 completed weekly assessments. Withdrawal, craving, and opioid or other drug use were significantly lower during induction and after XR-NTX administration compared with baseline, and no serious adverse events were recorded. CONCLUSIONS Outpatient transition to XR-NTX combining upward titration of very low dose naltrexone with downward titration of low dose buprenorphine was safe, well tolerated, and completed by most participants. Further studies with larger numbers of subjects are needed to see if this approach is useful for naltrexone induction. PMID:24602363

  10. HIV Risk Reduction With Buprenorphine-Naloxone or Methadone: Findings From A Randomized Trial

    PubMed Central

    Woody, George; Bruce, Douglas; Korthuis, P. Todd; Chhatre, Sumedha; Hillhouse, Maureen; Jacobs, Petra; Sorensen, James; Saxon, Andrew J.; Metzger, David; Ling, Walter

    2014-01-01

    Objectives Compare HIV injecting and sex risk in patients being treated with methadone (MET) or buprenorphine-naloxone (BUP). Methods Secondary analysis from a study of liver enzyme changes in patients randomized to MET or BUP who completed 24-weeks of treatment and had 4 or more blood draws. The initial 1:1 randomization was changed to 2:1 (BUP: MET) after 18 months due to higher dropout in BUP. The Risk Behavior Survey (RBS) measured past 30-day HIV risk at baseline and weeks 12 and 24. Results Among 529 patients randomized to MET, 391 (74%) were completers; among 740 randomized to BUP, 340 (46%) were completers; 700 completed the RBS. There were significant reductions in injecting risk (p< 0.0008) with no differences between groups in mean number of times reported injecting heroin, speedball, other opiates, and number of injections; or percent who shared needles, did not clean shared needles with bleach, shared cookers, or engaged in front/back loading of syringes. The percent having multiple sex partners decreased equally in both groups (p<0.03). For males on BUP the sex risk composite increased; for males on MET, the sex risk decreased resulting in significant group differences over time (p<0.03). For females, there was a significant reduction in sex risk (p<0.02) with no group differences. Conclusions Among MET and BUP patients that remained in treatment, HIV injecting risk was equally and markedly reduced, however MET retained more patients. Sex risk was equally and significantly reduced among females in both treatment conditions, but increased for males on BUP, and decreased for males on MET. PMID:24751432

  11. Enhancement of tolerance development to morphine in rats prenatally exposed to morphine, methadone, and buprenorphine

    PubMed Central

    2010-01-01

    Background Abuse of addictive substances is a serious problem that has a significant impact on areas such as health, the economy, and public safety. Heroin use among young women of reproductive age has drawn much attention around the world. However, there is a lack of information on effects of prenatal exposure to opioids on their offspring. In this study, an animal model was established to study effects of prenatal exposure to opioids on offspring. Methods Female pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) 2-4 mg/kg morphine (1 mg/kg increment per week), (3) 7 mg/kg methadone, and (4) 3 mg/kg buprenorphine, subcutaneously, once or twice a day from E3 to E20. The experiments were conducted on animals 8-12 weeks old and with body weight between 250 and 350 g. Results Results showed that prenatal exposure to buprenorphine caused higher mortality than other tested substance groups. Although we observed a significantly lower increase in body weight in all of the opioid-administered dams, the birth weight of the offspring was not altered in all treated groups. Moreover, no obvious behavioral abnormality or body-weight difference was noted during the growing period (8-12 weeks) in all offspring. When the male offspring received morphine injection twice a day for 4 days, the prenatally opioid-exposed rats more quickly developed a tolerance to morphine (as shown by the tail-flick tests), most notably the prenatally buprenorphine-exposed offspring. However, the tolerance development to methadone or buprenorphine was not different in offspring exposed prenatally to methadone or buprenorphine, respectively, when compared with that of the vehicle controlled group. Similar results were also obtained in the female animals. Conclusions Animals prenatally exposed to morphine, methadone, or buprenorphine developed tolerance to morphine faster than their controlled mates. In our animal model, prenatal exposure to buprenorphine also resulted in higher

  12. The Use of Transdermal Buprenorphine in Complex Regional Pain Syndrome: A Report of Two Cases.

    PubMed

    Onofrio, Sarah; Vartan, Christine M; Nazario, Mitchell; DiScala, Sandra; Cuevas-Trisan, Ramon; Melendez-Benabe, John

    2016-06-01

    Management of complex regional pain syndrome (CRPS) can be challenging. Various pharmacological approaches have produced mixed results. Buprenorphine activates mu-opioid receptors and antagonizes kappa and delta receptors, acts at N-methyl-d-aspartate (NMDA) receptor, and is an orphan-related ligand-1 receptor agonist. It is available in transdermal patches that last for up to 7 days. This report describes two patients with refractory CRPS who were treated with transdermal buprenorphine. The patients experienced approximately 50% reduction in pain intensity scores. Application site rash that occurred was managed with topical steroid spray used before applying the patch. PMID:27172230

  13. Illicit use of methadone and buprenorphine among adolescents and young adults in Sweden

    PubMed Central

    2013-01-01

    Background Illicit use of methadone and buprenorphine has been described as a growing problem in Sweden in recent years, and has been associated with an increased drug-related mortality. Critics claim that the substances have become popular among adolescents and that they function as a gateway to heroin use. The aim of this study is to investigate, firstly, the extent to which illicit use of methadone and buprenorphine occurs among adolescents and young adults in Sweden, and secondly, at what stage in a user’s drug career these substances tend to appear. Methods The study is based on surveys and structured interviews on drug use among various populations of young people, in addition to qualitative interviews with 86 informants who, in their professional capacity, encounter adolescents or young adults who are using illicit drugs. Results Illicit use of methadone and buprenorphine is rare among young people in Sweden. According to high school surveys, less than 0.1% have tried these substances. Among young drug users in general, few have tried the substances, and there is nothing to indicate that they act as gateway drugs. Among adolescents and young adults with severe drug problems, however, the illicit use of methadone and buprenorphine is more common (54% in a compulsory care sample). These substances normally enter the drug career late, and few use them as their main drug of choice. Other prescription drugs, like benzodiazepines and tramadol, are used by adolescents to a far greater extent. Diversion and illicit use of methadone and buprenorphine is not seen as a serious problem by the professionals interviewed. A general view is that the substances are mainly used by people with a heroin or polydrug addiction, often for “self-medication” purposes. However, several informants express concern that methadone and buprenorphine may cause fatalities among young drug users without an opioid tolerance. Conclusions Illicit use of methadone and buprenorphine among

  14. Amino acid substitutions in the hepatitis C virus core region of genotype 1b affect very early viral dynamics during treatment with telaprevir, peginterferon, and ribavirin.

    PubMed

    Akuta, Norio; Suzuki, Fumitaka; Hirakawa, Miharu; Kawamura, Yusuke; Yatsuji, Hiromi; Sezaki, Hitomi; Suzuki, Yoshiyuki; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Arase, Yasuji; Ikeda, Kenji; Kumada, Hiromitsu

    2010-04-01

    Substitution of amino acid (aa) 70 and 91 in the core region of hepatitis C virus (HCV) genotype 1b can predict the response to pegylated interferon (PEG-IFN)/ribavirin combination therapy, but its impact on triple therapy of telaprevir/PEG-IFN/ribavirin is not clear. The aims of this study were to investigate the rate of HCV RNA loss following 12-week triple therapy, and determine the effect of aa substitutions on very early (within 48 hr) viral dynamics. Sixty-seven patients infected with HCV genotype 1b (HCV-1b) and high viral load who received 12-week triple therapy were studied. RNA loss could be achieved in 2%, 34%, 80%, 92%, 95%, 94%, and 90% of the patients after 1, 2, 4, 6, 8, 10, and 12 weeks of triple therapy, respectively. After 24-hr treatment, the proportion of patients with Arg70 and Leu91 substitutions with > or = 3.0 log fall in HCV RNA was significantly higher than those with < 3.0 log fall (P = 0.008). However, the aa substitution patterns in the core region did not influence the fall in HCV RNA after 48-hr treatment. Multivariate analysis identified substitutions of aa 70 and 91 (P = 0.014) and level of viremia at baseline (> or = 7.0 log IU/ml; P = 0.085) as independent parameters that determined the > or = 3.0 log fall in HCV RNA level after 24-hr triple therapy. It is concluded that 12-week triple therapy achieved high rates of loss of HCV RNA in Japanese patients infected with HCV-1b and high viral load, and that the aa substitution pattern in the core region seems to influence very early viral dynamics. PMID:20166188

  15. Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs.

    PubMed

    Pieper, Korbinian; Schuster, Tibor; Levionnois, Olivier; Matis, Ulrike; Bergadano, Alessandra

    2011-03-01

    To assess the antinociceptive efficacy of transdermal (TD) buprenorphine (B) in dogs, a prospective, positive-controlled experimental study was performed in 10 healthy Beagles. In an open label crossover design, the dogs initially received intravenous B (IVB, 0.02 mg kg(-1)) as a positive control, followed by TDB (52.5 μg h(-1)) 4 months later. Blood was collected at regular intervals for determination of the plasma concentrations of B ([B]) and its metabolite norbuprenorphine. The antinociceptive efficacy was assessed using thermal and mechanical models of nociception. The peak concentration [B] was 1.54 ng mL(-1) (±1.98) 60 h after TDB application, although three dogs had no measurable [B] after TDB. Maximum thermal threshold (TT) was 52.6 °C (±0.48) at 1h after IVB administration and 51.63 °C (±1.01) 72 h after TDB application. The significant increase in TT indicated that effective antinociception was achieved beyond 36 h after the application of TDB, lasting until patch removal. There was hysteresis between [B] and the antinociceptive effect. PMID:20206560

  16. Buprenorphine and norbuprenorphine findings in hair during constant maintenance dosage.

    PubMed

    Skopp, Gisela; Kniest, Anja; Haisser, Joerg; Mann, Karl; Hermann, Derik

    2011-03-01

    It is still a matter of debate whether a positive correlation between the dose and the amount of drug in the hair exists. Drugs such as buprenorphine (BUP) used under controlled conditions present an opportunity to prove a possible relationship. Due to discrepant findings of BUP/norbuprenorphine (NBUP) ratios in hair, in vitro degradation of both analytes in diluted acid was also investigated. The levels of BUP and NBUP in proximal hair sections from 18 subjects participating in a maintenance program were determined by liquid chromatography/tandem mass spectrometry following incubation with methanol and subsequent liquid/liquid extraction. BUP and NBUP were incubated in diluted hydrochloric acid at 60°C for up to 24 h. The alleged rearrangement products were simultaneously monitored. All hair samples tested positive for BUP (lower limit of detection-0.238 ng/mg hair) and NBUP (0.043-0.961 ng/mg hair). The concentration of NBUP in hair was consistently higher than that of BUP except for a single specimen. Degradation of BUP and NBUP was dependent on time; hydrolysis of NBUP occurred faster than that of BUP. The concentration of BUP and NBUP will be underestimated if analytes are recovered by acidic procedures. NBUP should be monitored in hair samples besides BUP for the sum of both BUP and NBUP may provide an estimate of BUP exposure following long-term administration of the drug. PMID:21301858

  17. Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice

    PubMed Central

    DeTolla, L.; Sanchez, R.; Khan, E.; Tyler, B.; Guarnieri, M.

    2014-01-01

    Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3 mg/kg dose of drug. One male mouse treated with three 3 mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine. PMID:26464927

  18. Transplacental transfer and metabolism of buprenorphine in preterm human placenta.

    PubMed

    Fokina, Valentina M; Patrikeeva, Svetlana L; Zharikova, Olga L; Nanovskaya, Tatiana N; Hankins, Gary V D; Ahmed, Mahmoud S

    2011-01-01

    We sought to determine whether gestational age affects the transplacental transfer and metabolism of buprenorphine (BUP). Transfer of BUP (10 ng/mL) and its [ (3)H]-isotope was determined across placentas of 30 to 34 weeks of gestation utilizing the technique of dual perfusion of placental lobule. Concentration of the drug in trophoblast tissue and in maternal and fetal circuits was determined by liquid scintillation spectrometry. Microsomes prepared from placentas of 17 to 37 weeks of gestation were divided into three groups: late second, early third, and late third trimesters. Antibodies raised against human cytochrome P450 (CYP) isoforms were utilized to identify the enzyme(s) catalyzing BUP biotransformation by preterm placental microsomes. The amount of norbuprenorphine formed was determined by liquid chromatography-mass spectrometry (LC-MS). BUP transfer across the placentas of 30 to 34 weeks of gestation was similar to those at term. CYP19 antibodies caused 60% inhibition of BUP metabolism by microsomes of late second and early third trimesters and 85% by microsomes of late third trimester. The developmental changes occurring in human placenta between 30 weeks of gestation through term do not affect the transfer of BUP across human placenta. CYP19 is the major enzyme responsible for biotransformation of BUP beginning at 17 weeks of gestation until term. PMID:20607647

  19. Antidepressant-like Effects of Buprenorphine in Rats Are Strain Dependent

    PubMed Central

    Browne, Caroline A.; van Nest, Duncan; Lucki, Irwin

    2014-01-01

    The prevalence of major depressive disorder and the limited efficacy of conventional drug treatments provide significant impetus to develop novel and more rapidly acting antidepressants for individuals with treatment resistant forms of depression. The primary goal of these studies was to ascertain whether buprenorphine (BPN), a medically available drug with mixed effects at opioid receptors, was effective in behavioral tests using the Wistar Kyoto (WKY) rat strain, a rodent model of exaggerated depressive and anxiety behaviors that demonstrates resistance to certain antidepressants. As WKY rats are maintained by different sources, we assessed the behavioral effects of BPN using the modified rat forced swim test (FST) and the emergence test in WKY rat colonies obtained from different vendors. BPN dose-dependently reduced immobility and increased swimming behavior in the FST and reduced emergence latencies in two WKY lines (Charles River (WKY/NCrl) and Harlan laboratories (WKY/NHsd)) that also showed high baseline immobility in the FST. WKY rats from Taconic (WKY/NTac) did not show high baseline immobility in the FST or anxiety as had been previously reported, suggesting drift in the phenotype of rats from this supplier. Furthermore, BPN did not reduce immobility in the FST or reduce latencies in the emergence test in WKY rats from Taconic. BPN also failed to produce antidepressant-like effects in Wistar and Sprague-Dawley rats. These results indicate a striking strain-selectivity for the effects of BPN, producing antidepressant and anxiolytic-like responses in WKY/NCrl and WKY/NHsd lines but not in the normosensitive control Wistar and Sprague-Dawley strains. PMID:25453747

  20. A scoping review of home-produced heroin and amphetamine-type stimulant substitutes: implications for prevention, treatment, and policy.

    PubMed

    Hearne, Evelyn; Grund, Jean-Paul Cornelius; Van Hout, Marie Claire; McVeigh, Jim

    2016-01-01

    Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and internal organ damage. The high incidence of HIV rates amongst people who inject home-produced substances is a public health concern. The resulting physical health consequences of injecting these crude substances are very severe in comparison to heroin or amphetamine acquired in black markets. Due to this fact and the increased mortality associated with these substances, professionals in the area of prevention, treatment, and policy development need to be cognisant of the presentation, harms, and the dangers associated with home-produced substances globally. This scoping review aimed to examine existing literature on the subject of home-produced heroin and amphetamine-type stimulant substitutes. The review discussed the many implications such research may have in the areas of policy and practice. Data were gathered through the use of qualitative secondary resources such as journal articles, reports, reviews, case studies, and media reports. The home production of these substances relies on the utilisation of precursor drugs such as less potent stimulants, tranquillizers, analgesics, and sedatives or natural plant ingredients. The Internet underpins the facilitation of this practice as recipes, and diverted pharmaceutical sales are available widely online, and currently, ease of access to the Internet is evident worldwide. This review highlights the necessity of prevention, education, and also harm reduction related to home-produced drugs and also recommends consistent monitoring

  1. Orthodontic Treatment of a Patient with Bilateral Congenitally Missing Maxillary Canines: The Effects of First Premolar Substitution on the Functional Outcome.

    PubMed

    Sumiyoshi, Kumi; Ishihara, Yoshihito; Komori, Hiroki; Yamashiro, Takashi; Kamioka, Hiroshi

    2016-01-01

    Permanent canines are thought to play a pivotal role in obtaining an ideal occlusion. Dentists occasionally encounter patients who lack canines and are therefore missing a key to harmonious guidance during functional mandibular excursions. This case report describes the substitution of maxillary first premolars for congenitally missing canines in the context of an orthodontic treatment plan. A boy, age 10 years and 11 months, with a chief complaint of crooked teeth was diagnosed with Class II division 2 malocclusion associated with a high mandibular plane angle and deep overbite. A stable occlusion with a satisfactory facial profile and functional excursions without interference were achieved after a comprehensive two-stage orthodontic treatment process. The resulting occlusion and satisfactory facial profile were maintained for 12 months. These results indicate that substituting the first premolars for the canines is an effective option in treating patients with missing canines while maintaining functional goals. PMID:26899611

  2. Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers

    PubMed Central

    Fischer, Andreas; Hjelmström, Peter

    2015-01-01

    Abstract Context Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. Objective To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Methods Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv®), using sucralose and menthol as sweetener and flavor to mask the bitter taste of the active ingredients. Two cross-over studies were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time and acceptability of OX219 5.7/1.4 mg tablets compared to the commercially available buprenorphine/naloxone formulations Suboxone® tablets and films (8/2 mg). Results Buprenorphine exposure was equivalent in OX219 and Suboxone tablets. Sublingual dissolve times were significantly shorter for OX219 than for Suboxone tablets and were similar to Suboxone films. The OX219 formulation received significantly higher subjective ratings for taste and overall acceptability than both Suboxone formulations. OX219 was preferred over Suboxone tablet and film formulations by 77.4% and 88.9% of subjects, respectively. Conclusions A sublingual tablet formulation with an improved acceptability has been successfully developed. PMID:24099551

  3. The safety of high-dose buprenorphine administered subcutaneously in cats.

    PubMed

    Sramek, M K; Haas, M C; Coleman, G D; Atterson, P R; Hamlin, R L

    2015-10-01

    The safety of a proprietary formulation of buprenorphine hydrochloride administered subcutaneously (SC) to young cats was investigated in a blinded, randomized study. Four cohorts of eight cats aged approximately 4 months were administered saline, 0.24, 0.72 or 1.20 mg/kg/day buprenorphine SC for nine consecutive days, representing 0×, 1×, 3× and 5× of the intended dose. Cats were monitored daily for evidence of clinical reactions, food and water intake and adverse events (AEs). Physical examinations, clinical pathology, vital signs and electrocardiograms (ECGs) were evaluated at protocol-specified time points. Complete necropsy and histopathologic examinations were performed following humane euthanasia. Four buprenorphine-treated cats experienced AEs during the study, two unrelated and two related to study drug administration. The two cats with AEs considered related to drug administration had clinical signs of hyperactivity, difficulty in handling, disorientation, agitation and dilated pupils in one 0.24 mg/kg/day cat and one 0.72 mg/kg/day cat. All of these clinical signs were observed simultaneously. There were no drug-related effects on survival, injection response, injection site inspections, body weight, food or water consumption, bleeding time, urinalysis, respiration rate, heart rate, ECGs, blood pressures, body temperatures, macroscopic examinations or organ weights. Once daily buprenorphine s.c. injections at doses of 0.24, 0.72 and 1.20 mg/kg/day for 9 consecutive days were well tolerated in young domestic cats. PMID:25623082

  4. Pharmacokinetics of buprenorphine following intravenous and intramuscular administration in male rhesus macaques (Macaca mulatta)

    PubMed Central

    Kelly, Kristi R.; Pypendop, Bruno H.; Christe, Kari L.

    2014-01-01

    This study reports the pharmacokinetics of buprenorphine in conscious rhesus macaques (Macaca mulatta) after intravenous (IV) and intramuscular (IM) administration. Four healthy, opioid-naïve, socially-housed, adult male macaques were used. Buprenorphine (0.03 mg/kg) was administered intravenously as a bolus or intramuscularly on separate occasions. Blood samples were collected prior to, and up to 24 h, post-administration. Serum buprenorphine concentrations were analyzed with liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed with commercially available software. Mean residence time in the IV study as compared to the IM study was 177 (159–189) minutes vs. 185 (174–214) minutes, respectively [median (range)]. In the IV study, concentration back extrapolated to time zero was found to be 33.0 (16.8–57.0) ng/mL [median (range)]. On the other hand, the maximum serum concentration found in the IM study was 11.8 (6.30–14.8) ng/mL [median (range)]. Rhesus macaques maintained concentrations greater than 0.10 ng/mL for over 24 h in the IV study and over 12 h in the IM study. Bioavailability was found to be 68.1 (59.3–71.2)% [median (range)]. No significant adverse effects were observed in the monkeys at the 0.03 mg/kg dose of buprenorphine during either study. PMID:24666428

  5. Evaluation of a Sustained-Release Formulation of Buprenorphine for Analgesia in Rats

    PubMed Central

    Foley, Patricia L; Liang, Haixiang; Crichlow, Andrew R

    2011-01-01

    Preventing and minimizing pain in laboratory animals is a basic tenet of biomedical research and is warranted for ethical, legal, and scientific reasons. Postoperative analgesia is an important facet of pain management. A sustained-release formulation of buprenorphine was tested in rats for analgesic efficacy and plasma concentration over a 72-h time period. Rats were injected subcutaneously with either 1.2 mg/kg sustained-release formulation (Bup-SR), 0.2 mL/kg buprenorphine HCl (Bup-HCl), or an equivalent volume of sustained-release vehicle and tested in a thermal nociception model or a surgical postoperative pain model. In both models, Bup-SR showed evidence of providing analgesia for 2 to 3 d. Thermal latency response in rats that received the sustained-release formulation increased 28.4% and 15.6% compared with baseline values on days 1 and 2, respectively. Rats with a unicortical tibial defect and treated with Bup-SR showed similar willingness to bear weight on the hindlimbs as did negative-control animals (no surgery), demonstrated by counting vertical raises; rats treated with Bup-HCl had significantly fewer vertical raises than did control rats for 5 d after surgery. Plasma concentrations of buprenorphine remained over 1 ng/mL for 72 h after a single dose of Bup-SR. Taken together, the results indicate that this formulation of buprenorphine may be a viable option for treating postsurgical pain in laboratory rats. PMID:21439213

  6. Improved memory for reward cues following acute buprenorphine administration in humans.

    PubMed

    Syal, Supriya; Ipser, Jonathan; Terburg, David; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Bos, Peter A; Montoya, Estrella R; Stein, Dan J; van Honk, Jack

    2015-03-01

    In rodents, there is abundant evidence for the involvement of the opioid system in the processing of reward cues, but this system has remained understudied in humans. In humans, the happy facial expression is a pivotal reward cue. Happy facial expressions activate the brain's reward system and are disregarded by subjects scoring high on depressive mood who are low in reward drive. We investigated whether a single 0.2mg administration of the mixed mu-opioid agonist/kappa-antagonist, buprenorphine, would influence short-term memory for happy, angry or fearful expressions relative to neutral faces. Healthy human subjects (n38) participated in a randomized placebo-controlled within-subject design, and performed an emotional face relocation task after administration of buprenorphine and placebo. We show that, compared to placebo, buprenorphine administration results in a significant improvement of memory for happy faces. Our data demonstrate that acute manipulation of the opioid system by buprenorphine increases short-term memory for social reward cues. PMID:25569708

  7. Antidotal effects of buprenorphine on the behavioral alterations accompanying cocaine and combined cocaine-ethanol toxicity.

    PubMed

    Hayase, Tamaki; Yamamoto, Yoshiko; Yamamoto, Keiichi

    2002-01-01

    The present study examined the effects of buprenorphine (BUP), a mixed opioid agonist-antagonist, on the behaviors accompanying cocaine (COCA) and combined cocaine-ethanol (EtOH) toxicity in the surviving mice. Using the activity-counting instrument Supermex, the relationship between the toxic signs and the corresponding behavioral alterations could be assessed. In the COCA-only group, a prolonged increase in the activity counts was caused by a high dose of COCA (75 mg/kg ip). Furthermore, this COCA-induced hyperactivity included ataxic behaviors that were accompanied by visible toxic signs, which were not observed in the mice with no drug treatment. A depressive dose of EtOH (3 g/kg ip) did not significantly modify the mortality rate in the COCA-only group in spite of its anticonvulsant effects. However, the peak activity counts in the survivors were attenuated in the COCA-EtOH group as compared to the COCA-only group. BUP attenuated the mortality rate in both COCA and COCA-EtOH groups, even without any anticonvulsant effects, but the most effective dose differed between the COCA (BUP: 0.25 mg/kg ip) and COCA-EtOH (BUP: 0.5 mg/kg ip) groups. At these BUP doses, the prolonged suppression of the morbid hyperactivity in the COCA-BUP group and the restoration of normal behavior in the COCA-EtOH-BUP group both seemed to be correlated with a good prognosis in the survivors; there was an early recovery from an increased blood pressure (BP), increased heart rate (HR) and decreased respiratory rate (RR) in the COCA-BUP group, and an early recovery from a decreased BP, decreased HR and decreased RR in the COCA-EtOH-BUP group. PMID:11812504

  8. Antidepressant-like Effects of Buprenorphine are Mediated by Kappa Opioid Receptors.

    PubMed

    Falcon, Edgardo; Browne, Caroline A; Leon, Rosa M; Fleites, Vanessa C; Sweeney, Rachel; Kirby, Lynn G; Lucki, Irwin

    2016-08-01

    Previous studies have identified potential antidepressant effects of buprenorphine (BPN), a drug with high affinity for mu opioid receptor (MORs) and kappa opioid receptors (KORs) and some affinity at delta opioid receptor (DOR) and opioid receptor-like 1 (ORL-1) receptors. Therefore, these studies examined which opioid receptors were involved in BPN's effects on animal behavior tests sensitive to antidepressant drugs. The acute effects of BPN were tested in the forced swim test (FST) using mice with genetic deletion of individual opioid receptors or after pharmacological blockade of receptors. For evaluating the effects of BPN on chronic stress, separate groups of mice were exposed to unpredictable chronic mild stress (UCMS) for 3 weeks and treated with BPN for at least 7 days before behavioral assessment and subsequent measurement of Oprk1, Oprm1, and Pdyn mRNA expression in multiple brain regions. BPN did not reduce immobility in mice with KOR deletion or after pretreatment with norbinaltorphimine, even though desipramine remained effective. In contrast, BPN reduced immobility in MOR and DOR knockout mice and in mice pretreated with the ORL-1 antagonist JTC-801. UCMS reduced sucrose preference, decreased time in the light side of the light/dark box, increased immobility in the FST and induced region-specific alterations in Oprk1, Oprm1, and PDYN mRNA expression in the frontal cortex and striatum. All of these changes were normalized following BPN treatment. The KOR was identified as a key player mediating the effects of BPN in tests sensitive to antidepressant drugs in mice. These studies support further development of BPN as a novel antidepressant. PMID:26979295

  9. Skin Substitutes

    PubMed Central

    Howe, Nicole; Cohen, George

    2014-01-01

    In a relatively short timespan, a wealth of new skin substitutes made of synthetic and biologically derived materials have arisen for the purpose of wound healing of various etiologies. This review article focuses on providing an overview of skin substitutes including their indications, contraindications, benefits, and limitations. The result of this overview was an appreciation of the vast array of options available for clinicians, many of which did not exist a short time ago. Yet, despite the rapid expansion this field has undergone, no ideal skin substitute is currently available. More research in the field of skin substitutes and wound healing is required not only for the development of new products made of increasingly complex biomolecular material, but also to compare the existing skin substitutes. PMID:25371771

  10. Comparison of methadone and buprenorphine for opiate detoxification (LEEDS trial): a randomised controlled trial

    PubMed Central

    Wright, Nat MJ; Sheard, Laura; Adams, Clive E; Rushforth, Bruno J; Harrison, Wendy; Bound, Nicole; Hart, Roger; Tompkins, Charlotte NE

    2011-01-01

    Background Many opiate users require prescribed medication to help them achieve abstinence, commonly taking the form of a detoxification regime. In UK prisons, drug users are nearly universally treated for their opiate use by primary care clinicians, and once released access GP services where 40% of practices now treat drug users. There is a paucity of evidence evaluating methadone and buprenorphine (the two most commonly prescribed agents in the UK) for opiate detoxification. Aim To evaluate whether buprenorphine or methadone help to achieve drug abstinence at completion of a reducing regimen for heroin users presenting to UK prison health care for detoxification. Design Open-label, pragmatic, randomised controlled trial in three prison primary healthcare departments in the north of England. Method Prisoners (n = 306) using illicit opiates were recruited and given daily sublingual buprenorphine or oral methadone, in the context of routine care, over a standard reduced regimen of not more than 20 days. The primary outcome measure was abstinence from illicit opiates at 8 days post detoxification, as indicated by urine test (self-report/clinical notes where urine sample was not feasible). Secondary outcomes were also recorded. Results Abstinence was ascertained for 73.7% at 8 days post detoxification (urine sample = 52.6%, self report = 15.2%, clinical notes = 5.9%). There was no statistically significant difference in the odds of achieving abstinence between methadone and buprenorphine (odds ratio [OR] = 1.69; 95% confidence interval [CI] = 0.81 to 3.51; P = 0.163). Abstinence was associated solely with whether or not the participant was still in prison at that time (15.22 times the odds; 95% CI = 4.19 to 55.28). The strongest association for lasting abstinence was abstinence at an earlier time point. Conclusion There is equal clinical effectiveness between methadone and buprenorphine in achieving abstinence from opiates at 8 days post detoxification within prison

  11. Comparison between Transdermal Buprenorphine and Transdermal Fentanyl for Postoperative Pain Relief after Major Abdominal Surgeries

    PubMed Central

    Arshad, Zia; Gautam, Shefali; Kumar, Sanjeev

    2015-01-01

    Introduction Opioid is generally regarded as an important part of multimodal, perioperative analgesia, especially for moderate to severe pain. Amongst the various modes of delivery transdermal route has several potential benefits over oral and parentral administration. These include noninvasive dosing, better absorption and lack of first-pass metabolism. A transdermal drug delivery system provides steady and continuous drug delivery resulting in steady plasma concentration. Bolus dosing of systemic analgesic results in supra and sub therapeutic plasma resulting in toxic and sub analgesic plasma drug concentration. It also improves patient compliance. Materials and Methods Sixty patients undergoing major abdominal surgery under GA were randomly divided in two groups (n=30). Group A received buprenorphine 10 mcg/h TDS and group B received 25 mcg/h fentanyl TDS, 6 hours prior to surgery. Patients were followed for three days for postoperative pain relief and adverse effects. Results Baseline and demographic variables are comparable in both groups. The mean level of VAS was significantly lower in group B as compared to group A at Day 1, 2 and 3. The mean level of sedation score was significantly lower in Group B than Group A. Haemodynamic variables in both groups (SBP, DBP and HR), shows comparable values in both groups and no significant difference was observed. Five out of 30 (16.7%) patients in group A required single dose of rescue analgesic while 0 out of 30 patients (0.00%) in group B required rescue analgesic. This difference in rescue analgesic requirement in not quiet statistically significant (p-value 0.0522). Twenty percent patient in fentanyl group and 16.7% patients in buprenorphine group experienced some adverse effects. Nausea and vomiting were main side effects of the drugs. The incidence of nausea and vomiting were 6.7% and 10% in buprenorphine and fentanyl group respectively. Conclusion Fentanyl and buprenorphine TDS were effective and safe in

  12. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Project Study: protocol for a randomised controlled trial comparing methadone and buprenorphine for opiate detoxification

    PubMed Central

    Sheard, Laura; Wright, Nat MJ; Adams, Clive E; Bound, Nicole; Rushforth, Bruno; Hart, Roger; Tompkins, Charlotte NE

    2009-01-01

    Background In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin and many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are currently buprenorphine and methadone, both are recommended by national clinical guidelines. However, these agents have never been compared for opiate detoxification in the prison estate and there is a general paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address this paucity by evaluating the most routinely used interventions amongst drug users within UK prisons. Methods/Design This study uses randomised controlled trial methodology to compare the open use of buprenorphine and methadone for opiate detoxification, given in the context of routine care, within three UK prisons. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome will be abstinence status eight days after detoxification, as determined by a urine test. Secondary outcomes will be recorded during the detoxification and then at one, three and six months post-detoxification. Trial registration Current Controlled Trials ISRCTN58823759 PMID:19602218

  13. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project pilot study: protocol for a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification

    PubMed Central

    Sheard, Laura; Adams, Clive E; Wright, Nat MJ; El-Sayeh, Hany; Dalton, Richard; Tompkins, Charlotte NE

    2007-01-01

    Background In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin. Many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are buprenorphine, dihydrocodeine and methadone. However, national guidelines do not state a detoxification drug of choice. Indeed, there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons. Methods/Design The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Pilot Study will use randomised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification, given in the context of routine care, within HMP Leeds. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome measure will be abstinence status at five days post detoxification, as determined by a urine test. Secondary outcomes during the detoxification and then at one, three and six months post detoxification will be recorded. PMID:17210080

  14. Drug-resistance mutations number and K70R or T215Y/F substitutions predict treatment resumption during guided treatment interruptions.

    PubMed

    Darwich, Laila; Esteve, Anna; Ruiz, Lidia; Paredes, Roger; Bellido, Rocio; Cabrera, Cecilia; Romeu, Joan; Bofill, Margarita; Clotet, Bonaventura; Martinez-Picado, Javier

    2008-05-01

    The role of antiretroviral history and genotypic resistance information as predictors of the first treatment interruption (TI) length in a CD4(+) cell count and plasma viremia-guided TI study (GTI) was assessed. Drug-resistance mutations (DRMs) were monitored in chronically HIV-1-infected subjects who underwent GTI. Patients were retrospectively classified into those who received monotherapy or dual therapy prior to HAART (pre-HAART group, n = 44) or directly initiated HAART (HAART group, n = 43). DRMs were assessed by population-based sequencing of proviral DNA at baseline and plasma RNA monthly during TI up to 180 weeks. Univariate and multivariate Cox's proportional hazard models were used to determine time off therapy predictors. The emergence of viruses with DRMs during TI was 5.1-fold more likely in pre-HAART than in HAART patients. The presence of DRMs in proviral DNA or plasma RNA was associated with shorter time off therapy. An accumulation of three or more DRMs duplicated the risk of restarting therapy with respect to having one or two mutations. Regardless of the number of DRMs, the presence of K70R or T215F/Y predicted the shortest TI time. Multivariate analyses adjusted by nadir CD4(+) counts supported the presence of DRMs in plasma HIV-1 RNA, and specifically the K70R or T215F/Y, as potent predictors of time off therapy. A history of monotherapy or dual therapy, accumulation of three or more key DRMs in the HIV-1 polymerase, and/or the presence of substitutions K70R or T215F/Y were associated with shorter time off therapy during GTI. A genotypic profile could provide clinicians with a predictive tool for time off therapy when TI is required in patients with suppressed viremia in whom nadir CD4(+) count is not available. PMID:18462084

  15. Disposition in the rat of buprenorphine administered parenterally and as a subcutaneous implant.

    PubMed

    Pontani, R B; Vadlamani, N L; Misra, A L

    1985-04-01

    Disposition of [15, 16(n)-3H]buprenorphine in the rat has been investigated after a single 0.2 mg/kg i.v. bolus dose and continuous administration via a s.c. implantable long-acting delivery system. After the i.v. injection, the tri-exponential decay of drug from brain occurred with t1/2 values of 0.6, 2.3 and 7.2 h, respectively (plasma t1/2 0.5, 1.4 h, third phase not estimated due to sustained concn.) Decay of drug from another high-affinity binding site in brain occurred with t1/2 values of 1.1 and 68.7 h, respectively. Fat and lung had higher concn. than other tissues and plasma. No metabolites of drug were detected in brain. Unmetabolized drug excreted in urine and faeces one week after i.v. injection were 1.9 and 22.4% of dose, respectively, and 92% of the dose was accounted for in one week. Urinary metabolites (%) were: conjugated buprenorphine 0.9; norbuprenorphine (free 9.4, conjugated 5.2); tentative 6-O-desmethylnorbuprenorphine (free 5.4, conjugated 15.9). Peak plasma concn. of buprenorphine occurred four weeks after s.c. implantation of a long-acting 10 mg 3H-buprenorphine pellet, and apparent dissociation half-lives of drug from low- and high-affinity binding sites in brain were 4.6 and 6.8 weeks, respectively. Fat, spleen and skeletal muscle had higher concn. than other tissues and plasma. No significant difference in brain morphine concn. was observed in placebo and nonlabelled buprenorphine-pelleted animals after a 2 mg/kg i.v. challenge dose of 3H-morphine. This study emphasizes the importance of high-affinity binding of buprenorphine in brain and subsequent slow dissociation as a prime factor in its prolonged agonist/antagonist effects and higher potency than other narcotic agonists. PMID:4024663

  16. Design and optimization of a substituted amino propanamide series of renin inhibitors for the treatment of hypertension.

    PubMed

    Chen, Austin; Bayly, Christopher; Bezençon, Olivier; Richard-Bildstein, Sylvia; Dubé, Daniel; Dubé, Laurence; Gagné, Sébastien; Gallant, Michel; Gaudreault, Mireille; Grimm, Erich; Houle, Robert; Lacombe, Patrick; Laliberté, Sébastien; Lévesque, Jean-François; Liu, Suzanna; MacDonald, Dwight; Mackay, Bruce; Martin, David; McKay, Dan; Powell, David; Remen, L'ubos; Soisson, Stephen; Toulmond, Sylvie

    2010-04-01

    The discovery and SAR of a new series of substituted amino propanamide renin inhibitors are herein described. This work has led to the preparation of compounds with in vitro and in vivo profiles suitable for further development. Specifically, challenges pertaining to oral bioavailability, covalent binding and time-dependent CYP 3A4 inhibition were overcome thereby culminating in the identification of compound 50 as an optimized renin inhibitor with good efficacy in the hypertensive double-transgenic rat model. PMID:20206513

  17. [Delegation yes, substitution no!].

    PubMed

    Schroeder, A

    2014-08-01

    The aging of society leads on the one hand to increasing case numbers and on the other hand to a reduction in the number of physicians available for patient treatment. The delegation and substitution of medical duties as a tried and tested method is increasingly being recommended in order to compensate for the lack of physicians. The Berufsverband der Deutschen Urologen (BDU, Professional Association of German Urologists) supports the guiding principle of the Bundesärztekammer (Federal Medical Council) of "delegation yes, substitution no" and rejects a substitution of medical duties by non-medical academic health personnel. Against the background of the demographic changes, the increasing need for treatment and the current deficiency of junior physicians, a more extensive inclusion of well-qualified and experienced non-medical personnel by the delegation of medically responsible duties (medical scope of practice) can be an appropriate measure to maintain a good medical service in practices, hospitals and nursing homes. PMID:25047595

  18. Buprenorphine 5, 10 and 20 μg/h transdermal patch: a review of its use in the management of chronic non-malignant pain.

    PubMed

    Plosker, Greg L

    2011-12-24

    This article reviews the pharmacology, therapeutic efficacy and tolerability profile of the 7-day lower-dose (5, 10 and 20 μg/h) buprenorphine transdermal patch (BuTrans®, Norspan®) in the management of chronic non-malignant pain, with a focus on European labelling for the drug. Buprenorphine is a semi-synthetic opioid analgesic that acts primarily as a partial agonist at the mu opioid receptor. The transdermal formulation provides continuous delivery of buprenorphine, resulting in relatively consistent plasma drug concentrations throughout the 7-day dosing interval. The analgesic efficacy of transdermal buprenorphine in patients with osteoarthritis of the hip and/or knee has been demonstrated in several randomized controlled trials, which have shown the formulation to be equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol tablets, noninferior to codeine plus paracetamol (acetaminophen) combination tablets (when transdermal buprenorphine was used together with regularly scheduled oral paracetamol) and generally superior to a matching transdermal placebo patch. Transdermal buprenorphine was significantly more effective than placebo in reducing chronic low back pain of at least moderate severity in two randomized, double-blind, crossover trials. Other clinical trials, including a randomized, double-blind, maintenance-of-analgesia study, have also demonstrated the analgesic efficacy of transdermal buprenorphine in patients with chronic non-malignant pain of various causes. In general, serious adverse events with transdermal buprenorphine are similar to those for other opioid analgesics. Transdermal buprenorphine has a ceiling effect for respiratory depression, and the main risk is when it is combined with other CNS depressants. The most frequently reported adverse events with transdermal buprenorphine are headache, dizziness, somnolence, constipation, dry mouth, nausea, vomiting, pruritus, erythema, application site pruritus and

  19. Micro-oxidation treatment to improve bonding strength of Sr and Na co-substituted hydroxyapatite coatings for carbon/carbon composites

    NASA Astrophysics Data System (ADS)

    Zhang, Leilei; Li, Hejun; Li, Kezhi; Zhang, Yulei; Liu, Shoujie; Guo, Qian; Li, Shaoxian

    2016-08-01

    To improve the bonding strength of Sr and Na co-substituted hydroxyapatite (SNH) coatings for carbon/carbon composites, carbon/carbon composites are surface modified by micro-oxidation treatment. The micro-oxidation treatment could generate large number of pores containing oxygenic functional groups on the surface of carbon/carbon composites. SNH is nucleated on the inwall of the pores and form a flaky shape coating with 10-50 nm in thickness and 200-900 nm in width. The bonding strength between SNH coating and carbon/carbon composites increases from 4.27 ± 0.26 MPa to 10.57 ± 0.38 MPa after the micro-oxidation treatment. The promotion of bonding strength is mainly attributed to the pinning effect caused by the pores and chemical bonding generated by the oxygenic functional groups.

  20. New Pain Management Options for the Surgical Patient on Methadone and Buprenorphine.

    PubMed

    Sen, Sudipta; Arulkumar, Sailesh; Cornett, Elyse M; Gayle, Julie A; Flower, Ronda R; Fox, Charles J; Kaye, Alan D

    2016-03-01

    Perioperative management of patients receiving opioid addiction therapy presents a unique challenge for the anesthesiologist. The goal of pain management in this patient population is to effectively manage postoperative pain, to improve patient satisfaction and outcomes, and to reduce the cost of health care. Multimodal analgesics, including nonsteroid anti-inflammatory drugs, intravenous acetaminophen, gabapentanoid agents, and low-dose ketamine infusions, have been used to improve postoperative pain and to reduce postoperative opioid use. Patients on long-term opioid management therapy with methadone and buprenorphine require special considerations. Recommendations and options for treating postoperative pain in patients on methadone and buprenorphine are outlined below. Other postoperative pain management options include patient-controlled analgesia, intravenous, and transdermal, in addition to neuraxial and regional anesthesia techniques. Special patient populations include the parturient on long-term opioid therapy. Recommendations for use of opioids in these patients during labor and delivery and in the postpartum period are discussed. PMID:26879874

  1. Buprenorphine and Norbuprenorphine Determination in Mice Plasma and Brain by Gas Chromatography–Mass Spectrometry

    PubMed Central

    Chiadmi, Fouad; Schlatter, Joël

    2014-01-01

    A gas chromatography tandem mass spectrometry method for quantification of buprenorphine (BUP) and norbuprenorphine (NBUP) in brain and plasma samples from mice was developed and validated. Analytes were extracted from the brain or plasma by solid phase extraction and quantified within 20 minutes. Calibration was achieved by linear regression with a 1/x weighting factor and d4-buprenorphine internal standard. All products were linear from 1 to 2000 ng/mL with a correlation of determination >0.99. Assay accuracy and precision of back-calculated standards were within ±10%. The lower limit of quantification for both BUP and NBUP from the brain and plasma was 1 ng/mL. This sensitive and specific method can be used for the investigation of BUP mechanism of action and clinical profile. PMID:24653644

  2. Buprenorphine and norbuprenorphine determination in mice plasma and brain by gas chromatography-mass spectrometry.

    PubMed

    Chiadmi, Fouad; Schlatter, Joël

    2014-01-01

    A gas chromatography tandem mass spectrometry method for quantification of buprenorphine (BUP) and norbuprenorphine (NBUP) in brain and plasma samples from mice was developed and validated. Analytes were extracted from the brain or plasma by solid phase extraction and quantified within 20 minutes. Calibration was achieved by linear regression with a 1/x weighting factor and d4-buprenorphine internal standard. All products were linear from 1 to 2000 ng/mL with a correlation of determination >0.99. Assay accuracy and precision of back-calculated standards were within ±10%. The lower limit of quantification for both BUP and NBUP from the brain and plasma was 1 ng/mL. This sensitive and specific method can be used for the investigation of BUP mechanism of action and clinical profile. PMID:24653644

  3. Comparison of the analgesic effects of robenacoxib, buprenorphine and their combination in cats after ovariohysterectomy.

    PubMed

    Staffieri, F; Centonze, P; Gigante, G; De Pietro, L; Crovace, A

    2013-08-01

    The aim of this study was to compare the postoperative analgesic effects of robenacoxib and buprenorphine alone or in combination, in cats after ovariohysterectomy. Thirty healthy cats were randomly assigned to receive buprenorphine (0.02 mg/kg, n=10; GB), robenacoxib (2mg/kg, n=10; GR) or their combination at the same dosages (n=10; GBR) SC. After 30 min cats were sedated with an IM administration of medetomidine (0.02 mg/kg) and ketamine (5mg/kg). General anaesthesia was induced with propofol and after intubation was maintained with isoflurane. Before premedication and at 1, 2, 3, 4, 6, 8, 12 and 24h after extubation, pain and sedation were assessed using a simple descriptive pain scale, ranging from 0 (no pain/no sedation) to 4 (intense pain/ deep sedation). If the pain score was ≥ 3, rescue analgesia was provided using buprenorphine (0.02 mg/kg) administered IM. Pain score was higher in GB at 2, 3, 4, 6 and 8h compared to baseline and compared to GBR at the same study times. Moreover, the pain score was also higher in GB compared to GR at 2, 3, 4 and 6h. Pain score was similar at all study times between GR and GBR. Sedation at 1 and 2h was higher than baseline values in all groups. Cats in GB received rescue analgesia more often than cats assigned to GR or GBR. Robenacoxib was an effective analgesic drug in cats up to 24h after ovariohysterectomy. The addition of buprenorphine did not provide any additional analgesic effects compared to robenacoxib alone. PMID:23434263

  4. Agonist treatment in opioid use: advances and controversy.

    PubMed

    Viswanath, Biju; Chand, Prabhat; Benegal, Vivek; Murthy, Pratima

    2012-06-01

    Opioid dependence is a chronic relapsing condition which requires comprehensive care; pharmacological agents form the mainstay of its long term treatment. The two most popular approaches are the harm reduction method using agonists and the complete abstinence method using antagonists. Currently, particularly from the harm minimization perspective and the low feasibility of an abstinence based approach, there is an increasing trend toward agonist treatment. The use of buprenorphine has gained popularity in view of its safety profile and the availability of the buprenorphine-naloxone combination has made it popular as a take-home treatment. This review outlines the pharmacological advances and controversies in this area. PMID:22813654

  5. The Influence of Hyperbaric Oxygen Treatment on the Healing of Experimental Defects Filled with Different Bone Graft Substitutes

    PubMed Central

    Sirin, Yigit; Olgac, Vakur; Dogru-Abbasoglu, Semra; Tapul, Leyla; Aktas, Samil; Soley, Sinan

    2011-01-01

    To assess potential effects of hyperbaric oxygen (HBOT) on artificial bone grafts, β - Tricalcium phosphate (β-TCP) and calcium phosphate coated bovine bone (CPCBB) substitutes were applied to standard bone defects in rat tibiae. The control defects were left empty. Half of the animals received 60 minutes of 2.4 atmosphere absolute (ATA) of HBOT. Rats were sacrificed at one, two and four weeks. Bone healing was assessed histologically and histomorphometrically using light microscopy. The periosteum over the bone defects was examined ultrastructurally. Cardiac blood was collected to determine the serum osteocalcin levels. The HBOT increased new bone formation in the unfilled controls and β-TCP groups and significantly decreased cartilage matrix and fibrous tissue formations in all groups. Active osteoblasts and highly organized collagen fibrils were prominent in the periosteum of β-TCP and control groups. Serum osteocalcin levels also increased with HBOT. The healing of defects filled with CPCBB was similar to the controls and it did not respond to HBOT. These findings suggested that the HBOT had beneficial effects on the healing of unfilled bone defects and those filled with β-TCP bone substitute but not with CPCBB, indicating a material-specific influence pattern of HBOT. PMID:21326954

  6. Fairness heuristics and substitutability effects: inferring the fairness of outcomes, procedures, and interpersonal treatment when employees lack clear information.

    PubMed

    Qin, Xin; Ren, Run; Zhang, Zhi-Xue; Johnson, Russell E

    2015-05-01

    Employees routinely make judgments of 3 kinds of justice (i.e., distributive, procedural, and interactional), yet they may lack clear information to do so. This research examines how justice judgments are formed when clear information about certain types of justice is unavailable or ambiguous. Drawing from fairness heuristic theory, as well as more general theories of cognitive heuristics, we predict that when information for 1 type of justice is unclear (i.e., low in justice clarity), people infer its fairness based on other types of justice with clear information (i.e., high in justice clarity). Results across 3 studies employing different designs (correlational vs. experimental), samples (employees vs. students), and measures (proxy vs. direct) provided support for the proposed substitutability effects, especially when inferences were based on clear interactional justice information. Moreover, we found that substitutability effects were more likely to occur when employees had high (vs. low) need for cognitive closure. We conclude by discussing the theoretical contributions and practical implications of our findings. PMID:25365727

  7. Development and validation of a highly sensitive GC/MS method for the determination of buprenorphine and nor-buprenorphine in blood.

    PubMed

    Papoutsis, Ioannis I; Nikolaou, Panagiota D; Athanaselis, Sotirios A; Pistos, Constantinos M; Spiliopoulou, Chara A; Maravelias, Constantinos P

    2011-02-20

    A sensitive and specific GC/MS method for the determination of buprenorphine (BPN) and its main metabolite nor-buprenorphine (nor-BPN) in blood has been developed, optimized and validated. Sample preparation includes solid-phase extraction of both analytes and their derivatization with acetic anhydride in pyridine. BPN-d4 was used as internal standard for the determination of both analytes. Limits of detection and quantification for BPN and nor-BPN were 0.02 and 0.05 μg/L, respectively. The calibration curves were linear within the dynamic range of each analyte (0.05-30.0 μg/L) with a correlation coefficient higher than 0.996. Absolute recovery ranged from 90.2 to 97.6% for both analytes and their internal standard. Intra- and inter-day accuracy was found to be between -5.40 to 1.73% and -2.45 to 2.80%, respectively, while intra- and inter-day precision were less than 5.8 and 4.7%, for both analytes. The method was applied to real blood samples obtained from patients that follow BPN maintenance program. The developed method can be used in routine every day analysis by clinical and forensic laboratories, for pharmacokinetic studies, for therapeutic drug level monitoring in order to adjust BPN dosage of BPN maintained patients or for the investigation of forensic cases. PMID:20940093

  8. A prospective multi-centre clinical trial to compare buprenorphine and butorphanol for postoperative analgesia in cats.

    PubMed

    Taylor, Polly M; Kirby, Jonathan J; Robinson, Clare; Watkins, Elizabeth A; Clarke, David D; Ford, Marion A; Church, Karen E

    2010-04-01

    One hundred and fifty-three cats undergoing surgery in seven veterinary practices in Great Britain were studied. They were randomly allocated to receive either 10-20 microg/kg buprenorphine or 0.4 mg/kg butorphanol with acepromazine before anaesthesia with propofol, Saffan or thiopentone and isoflurane or halothane. Routine monitoring was undertaken. Pain and sedation were assessed blind using a four point (0-3) simple descriptive scale (SDS) at 1, 2, 4, 8 and 24h. Pain and sedation data were compared using non-parametric statistical tests and continuous data using t tests or analysis of variance (ANOVA). Anaesthesia and surgery were uneventful, and cardiorespiratory data were within normal limits. After surgery, overall, more cats had pain score 0 after buprenorphine and more had pain score 3 after butorphanol (P=0.0465). At individual time points, more cats had lower pain scores after buprenorphine at 2 (P=0.040) and 24 (P=0.036)h. At 24h 83% after buprenorphine and 63% after butorphanol had pain score 0 (P<0.04). Buprenorphine provided better and longer lasting postoperative analgesia than butorphanol. PMID:19836984

  9. Sensory Substitution

    NASA Astrophysics Data System (ADS)

    Verrillo, Ronald T.

    The idea that the cutaneous surface may be employed as a substitute for the eyes and ears is by no means a modern notion. Although the sense of touch has long been considered as a surrogate for both the visual and auditory modalities, the focus of this chapter will be on the efforts to develop a tactile substitute for hearing, especially that of human speech. The visual system is our primary means of processing information about environmental space such as orientation, distance, direction and size. It is much less effective in making temporal discriminations. The auditory system is unparalleled in processing information that involves rapid sequences of temporal events, such as speech and music. The tactile sense is capable of processing both spatial and temporal information although not as effective in either domain as the eye or the ear.

  10. Use of mineralized collagen bone graft substitutes and dorsal locking plate in treatment of elder metaphyseal comminuted distal radius fracture

    NASA Astrophysics Data System (ADS)

    Liu, Ke-Bin; Huang, Kui; Teng, Yu; Qu, Yan-Zheng; Cui, Wei; Huang, Zhen-Fei; Sun, Ting-Fang; Guo, Xiao-Dong

    2014-03-01

    Bone graft may be needed to fill bone defect in elderly patients with a metaphyseal comminuted distal radius fracture. In this retrospective, nonrandomized, single-surgeon study, we evaluated the clinical and radiologic outcomes of using both dorsal locking plates with or without augmentation with mineralized collagen (MC) bone graft for elderly patients with dorsally metaphyseal comminuted radius fractures. Patients in group 1 ( n = 12) were treated with dorsal locking plates with MC bone graft application into the metaphyseal bone defect, and those in group 2 ( n = 12) only with dorsal locking plates. Clinical and radiologic parameters were determined at three and 12 months after surgery. At final follow-up, no significant difference was noted between the 2 groups in terms of palmar tilt and radial inclination ( p = 0.80); however, ulnar variance increased significantly in the group 2 treated with dorsal locking plates without augmentation ( p < 0.05). Functionally, there was no significant difference between the groups. Our preliminary study suggests that combination of MC as bone-graft substitutes and dorsal locking plates may be a usefully alternative for elderly patients with metaphyseal comminuted distal radius fracture.

  11. 7-Substituted umbelliferone derivatives as androgen receptor antagonists for the potential treatment of prostate and breast cancer.

    PubMed

    Kandil, Sahar; Westwell, Andrew D; McGuigan, Christopher

    2016-04-15

    The clinically used androgen receptor (AR) antagonists (bicalutamide, flutamide and nilutamide) bind with low affinity to AR and can induce escape mechanisms. Furthermore, under AR gene amplification or mutation conditions they demonstrate agonist activity and fail to inhibit AR, causing relapse into castration resistant prostate cancer (CRPC). Discovery of new scaffolds distinct from the 4-cyano/nitro-3-(trifluoromethyl)phenyl group common to currently used antiandrogens is urgently needed to avoid cross-resistance with these compounds. In this study, a series of twenty-nine 7-substituted umbelliferone derivatives was prepared and their antiproliferative activities were evaluated. The most active compound 7a demonstrated submicromolar inhibitory activity in the human prostate cancer cell line (22Rv1); IC50=0.93μM which represents a 50 fold improvement over the clinical antiandrogen bicalutamide (IC50=46μM) and a more than 30 fold improvement over enzalutamide (IC50=32μM). Interestingly, this compound showed even better activity against the human breast cancer cell line (MCF-7); IC50=0.47μM. Molecular modelling studies provided a plausible theoretical explanation for our findings. PMID:26965862

  12. Relative efficacy of cash versus vouchers in engaging opioid substitution treatment clients in survey-based research.

    PubMed

    Topp, Libby; Islam, M Mofizul; Day, Carolyn Ann

    2013-04-01

    Concerns that cash payments to people who inject drugs (PWID) to reimburse research participation will facilitate illicit drug purchases have led some ethical authorities to mandate department store/supermarket vouchers as research reimbursement. To examine the relative efficacy of the two forms of reimbursement in engaging PWID in research, clients of two public opioid substitution therapy clinics were invited to participate in a 20-30 min, anonymous and confidential interview about alcohol consumption on two separate occasions, 4 months apart. Under the crossover design, at Time 1, clients of Clinic 1 were offered $A20 cash as reimbursement, while clients of Clinic 2 were offered an $A20 voucher; at Time 2, the form of reimbursement was reversed. Using clinic records to determine the denominator (number of clients dosed), we found that compared with clients offered a voucher, a significantly higher proportion of clients who were offered cash participated in the survey (58% (139/241) vs 74% (186/252); χ(2)=14.27; p=0.0002). At first participation, respondents most commonly reported planning to purchase food/drinks/groceries (68%), cigarettes (21%) and transport/fuel (11%) with their payments, with those reimbursed in cash more likely to report planning to fund transport/fuel (19% vs 1%; p<.01) and less likely to report planning to purchase food/drinks/groceries (62% vs 76%; p=0.02). Just three out of 155 cash participants reported planning to purchase illicit drugs with their payment. Results demonstrate that modest cash payments enhanced recruitment of this group, an important consideration given the challenges of delineating the parameters of a population defined by illegal activity, seemingly without promoting excessive additional drug use. PMID:23236087

  13. An international perspective on using opioid substitution treatment to improve hepatitis C prevention and care for people who inject drugs: Structural barriers and public health potential.

    PubMed

    Perlman, David C; Jordan, Ashly E; Uuskula, Anneli; Huong, Duong Thi; Masson, Carmen L; Schackman, Bruce R; Des Jarlais, Don C

    2015-11-01

    People who inject drugs (PWID) are central to the hepatitis C virus (HCV) epidemic. Opioid substitution treatment (OST) of opioid dependence has the potential to play a significant role in the public health response to HCV by serving as an HCV prevention intervention, by treating non-injection opioid dependent people who might otherwise transition to non-sterile drug injection, and by serving as a platform to engage HCV infected PWID in the HCV care continuum and link them to HCV treatment. This paper examines programmatic, structural and policy considerations for using OST as a platform to improve the HCV prevention and care continuum in 3 countries-the United States, Estonia and Viet Nam. In each country a range of interconnected factors affects the use OST as a component of HCV control. These factors include (1) that OST is not yet provided on the scale needed to adequately address illicit opioid dependence, (2) inconsistent use of OST as a platform for HCV services, (3) high costs of HCV treatment and health insurance policies that affect access to both OST and HCV treatment, and (4) the stigmatization of drug use. We see the following as important for controlling HCV transmission among PWID: (1) maintaining current HIV prevention efforts, (2) expanding efforts to reduce the stigmatization of drug use, (3) expanding use of OST as part of a coordinated public health approach to opioid dependence, HIV prevention, and HCV control efforts, (4) reductions in HCV treatment costs and expanded health system coverage to allow population level HCV treatment as prevention and OST as needed. The global expansion of OST and use of OST as a platform for HCV services should be feasible next steps in the public health response to the HCV epidemic, and is likely to be critical to efforts to eliminate or eradicate HCV. PMID:26050614

  14. Confirmatory analysis of buprenorphine, norbuprenorphine, and glucuronide metabolites in plasma by LCMSMS. Application to umbilical cord plasma from buprenorphine-maintained pregnant women.

    PubMed

    Concheiro, Marta; Jones, Hendreé; Johnson, Rolley E; Shakleya, Diaa M; Huestis, Marilyn A

    2010-01-01

    An LCMSMS method was developed and fully validated for the simultaneous quantification of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine-glucuronide (BUP-Gluc), and norbuprenorphine-glucuronide (NBUP-Gluc) in 0.5mL plasma, fulfilling confirmation criteria with two transitions for each compound with acceptable relative ion intensities. Transitions monitored were 468.3>396.2 and 468.3>414.3 for BUP, 414.3>340.1 and 414.3>326.0 for NBUP, 644.3>468.1 and 644.3>396.3 for BUP-Gluc, and 590.3>414.3 and 590.3>396.2 for NBUP-Gluc. Linearity was 0.1-50ng/mL for BUP and BUP-Gluc, and 0.5-50ng/mL for NBUP and NBUP-Gluc. Intra-day, inter-day, and total assay imprecision (%RSD) were <16.8%, and analytical recoveries were 88.6-108.7%. Extraction efficiencies ranged from 71.1 to 87.1%, and process efficiencies 48.7 to 127.7%. All compounds showed ion enhancement, except BUP-Gluc that demonstrated ion suppression: variation between 10 different blank plasma specimens was <9.1%. In six umbilical cord plasma specimens from opioid-dependent pregnant women receiving 14-24mg/day BUP, NBUP-Gluc was the predominant metabolite (29.8+/-7.6ng/mL), with BUP-Gluc (4.6+/-4.8ng/mL), NBUP (1.5+/-0.8ng/mL) and BUP (0.4+/-0.2ng/mL). Although BUP biomarkers can be quantified in umbilical cord plasma in low ng/mL concentrations, the significance of these data as predictors of neonatal outcomes is currently unknown. PMID:19945361

  15. Intrathecal buprenorphine versus fentanyl as adjuvant to 0.75% ropivacaine in lower limb surgeries

    PubMed Central

    Singh, Arvinder Pal; Kaur, Ravinder; Gupta, Ruchi; Kumari, Anita

    2016-01-01

    Background and Aims: This study aims to compare the anesthesia characteristics between buprenorphine and fentanyl when added as an adjuvant to intrathecal ropivaciane in an attempt to prolong the duration of spinal anesthesia. Material and Methods: The present prospective double-blind study was undertaken on ninety American Society of Anesthesiologist I and II patients between 18 and 60 years of age undergoing subarachnoid block for lower limb surgery. Group I (n = 30) patients were administered 3 ml of intrathecal solution (2.8 ml of 0.75% ropivacaine + 0.2 ml of isotonic sodium chloride), while Groups II and III patients (n = 30 each) received 2.8 ml 0.75% ropivacaine + 0.2 ml buprenorphine (60 μg) and 2.8 ml 0.75% ropivacaine + 0.2 ml fentanyl (10 μg), respectively. Following parameters were observed: Onset times and duration of sensory and motor block, time to first analgesic use, total dose of rescue analgesia, intra- and post-operative pain scores based on visual analog scale, sedation scores, hemodynamic parameters, and side effects if any. Data were analyzed by appropriate statistical tests and P < 0.05 were considered significant. Results: Time to onset of sensory and motor block in all the three groups was comparable. However, duration of sensory block was significantly prolonged in Groups II and III in comparison to Group I (P < 0.05) and it was the longest in Group II (P < 0.05). The duration of motor blockade was similar in all the three groups. The time to first analgesic dose was also significantly prolonged in Groups II and III as compared to Group I (P < 0.05) but was comparable between Groups II and III. Intra- and post-operative hemodynamic parameters, as well as side effects, were comparable. Conclusion: Addition of buprenorphine and fentanyl as adjuvants to intrathecal 0.75% ropivacaine prolongs postoperative pain relief without causing any increase in the duration of motor blockade but buprenorphine is better as compared to fentanyl in

  16. Influence of detomidine and buprenorphine on motor-evoked potentials in horses.

    PubMed

    Nollet, H; Van Ham, L; Gasthuys, F; Dewulf, J; Vanderstraeten, G; Deprez, P

    2003-04-26

    Horses need to be sedated before they are investigated by transcranial magnetic stimulation because of the mild discomfort induced by the evoked muscle contraction and the noise of stimulation. This paper describes the influence of a combination of detomidine (10 microg/kg bodyweight) and a low dose of buprenorphine (2.4 microg/kg) on the onset latency and peak-to-peak amplitude of magnetic motor-evoked potentials in normal horses. There were no significant differences between measurements of these parameters made before the horses were sedated and measurements made 10 and 30 minutes after the drugs were administered. PMID:12739602

  17. High dose of buprenorphine in terminally ill patient with liver failure: efficacy and tolerability.

    PubMed

    Ciccozzi, Alessandra; Angeletti, Chiara; Baldascino, Giada; Petrucci, Emiliano; Bonetti, Cristina; De Santis, Stefania; Paladini, Antonella; Varrassi, Giustino; Marinangeli, Franco

    2012-01-01

    Pain in terminally ill patients with cancer can be often hard to manage, due to the unpredictable kinetics of drugs caused by progressive kidney and liver dysfunction. Plasma concentrations of active metabolites-also a cause of dangerous side effects--could be difficult to estimate. This case report holds the idea that buprenorphine, a partial agonist of m-receptors, even at high dosage, may be effective and safe to use in terminally ill patients with significant liver and kidney impairment. PMID:22941853

  18. Effect of partial substitution of invert sugar for sucrose in combination with Duraphat treatment on caries development in preschool children: the Malmö Study.

    PubMed

    Frostell, G; Birkhed, D; Edwardsson, S; Goldberg, P; Petersson, L G; Priwe, C; Winholt, A S

    1991-01-01

    The aim was to study the effect of substitution of invert sugar for sucrose, in combination with fluoride varnish (Duraphat) treatment twice a year, on caries development in preschool children. One hundred and eighty-seven 4-years-olds were divided randomly into four sugar groups: (1) sucrose (S), (2) sucrose-Duraphat (SD), (3) invert sugar (I), and (4) invert sugar-Duraphat (ID). All families were asked to buy beverages, biscuits, breakfast cereals, marmalade, ice cream, jam, ketchup, sweets and table sugar, totally 32 different food items, sweetened with invert sugar or sucrose. The substitution was, thus, restricted to a number of sugar-rich between-meal products. The study was carried out double-blind for 2 years. The children of those parents who did not want to participate in the sugar groups were divided randomly into one of the following two groups: (5) Duraphat (D), and control (C). Because of lack of cooperation, only 114 of the 187 children (61%) were considered to have completed the study. The mean caries increment, including initial lesions, was 3.86 dmfs in the combined groups S and SD (n = 63) and 3.10 dmfs in the combined groups I and ID (n = 51) during the 2 years (p = 0.34). The corresponding values for the 2nd year only were 1.84 and 0.67 dmfs, respectively (p = 0.09). The mean caries increment was 2.86 dmfs in group D (n = 113) and 4.10 dmfs (p = 0.08) in group C (n = 93). If initial caries lesions were excluded from the index, the difference between groups D and C was significant (p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1913770

  19. Analgesic Effects of Tramadol, Tramadol–Gabapentin, and Buprenorphine in an Incisional Model of Pain in Rats (Rattus norvegicus)

    PubMed Central

    McKeon, Gabriel P; Pacharinsak, Cholawat; Long, Charles T; Howard, Antwain M; Jampachaisri, Katechan; Yeomans, David C; Felt, Stephen A

    2011-01-01

    Postoperative pain management in laboratory animals relies heavily on a limited number of drug classes, such as opioids and nonsteroidal antiinflammatory drugs. Here we evaluated the effects of saline, tramadol, tramadol with gabapentin, and buprenorphine (n = 6 per group) in a rat model of incisional pain by examining thermal hyperalgesia and weight-bearing daily for 6 d after surgery. All drugs were administered preemptively and continued for 2 consecutive days after surgery. Rats treated with saline or with tramadol only showed thermal hyperalgesia on days 1 through 4 and 1 through 3 after surgery, respectively. In contrast, buprenorphine-treated rats showed no thermal hyperalgesia on days 1 and 2 after surgery, and rats given tramadol with gabapentin showed reduced thermal hyperalgesia on days 2 and 4. For tests of weight-bearing, rats treated with saline or with tramadol only showed significantly less ipsilateral weight-bearing on day 1 after surgery, whereas rats given either buprenorphine or tramadol with gabapentin showed no significant change in ipsilateral weight-bearing after surgery. These data suggest that tramadol alone provides insufficient analgesia in this model of incisional pain; buprenorphine and, to a lesser extent, tramadol with gabapentin provide relief of thermal hyperalgesia and normalize weight-bearing. PMID:21439212

  20. The magnitude and duration of the analgesic effect of morphine, butorphanol, and buprenorphine in rats and mice.

    PubMed

    Gades, N M; Danneman, P J; Wixson, S K; Tolley, E A

    2000-03-01

    This study was designed to determine the magnitude and duration of the analgesic effect of three commonly used opioids: buprenorphine (0.5 mg/kg for rats; 2.0 mg/kg for mice), butorphanol (2.0 mg/kg for rats; 5.0 mg/kg for mice), and morphine (10 mg/kg for rats and mice). We used two standard tests, the hot plate and tail flick assays, to measure opioid analgesia in 62 male, 200 to 300 g Sprague-Dawley rats and 61 male, 25 to 35 g ICR mice. We obtained five baseline measurements then administered the drugs subcutaneously. Morphine gave the highest analgesic effect and was intermediate in duration (2 to 3 h in rats and mice) of analgesia. Butorphanol provided the lowest level of and shortest (1 to 2 h in rats and mice) analgesia. Buprenorphine had an intermediate analgesic effect and the longest duration (6 to 8 h in rats and 3 to 5 h in mice). In light of our results, we recommend the use of morphine (with frequent redosing) for severe pain, butorphanol for mild pain of short duration, and buprenorphine for mild to moderate pain of increased duration. The dosing intervals suggested by our study are 2 to 3 h for morphine in both rats and mice, 1 to 2 h for butorphanol in both rats and mice; and 6 to 8 h in rats and 3 to 5 h in mice for buprenorphine. PMID:11487232

  1. Sequential Use of Hyperbaric Oxygen, Synthetic Skin Substitute and Skin Grafting in the Treatment of a Refractory Vasculitic Ulcer

    PubMed Central

    Akcali, Gökhan; Uzun, Günalp; Yapici, Abdül Kerim; Yildiz, Şenol

    2015-01-01

    Cutaneous leukocytoclastic vasculitis (CLCV) is a disorder characterized by the inflammation of the small vessels of the skin. CLCV may cause recurrent, drug-resistant, non-healing ulcers. Herein, we present a patient with a recalcitrant ulcer caused by CLCV, who was successfully treated with hyperbaric oxygen therapy and skin grafting. There is not any particular therapy/product that will heal all type of wounds. We can achieve better results provided that wound care products and advanced treatments are used at the right time. PMID:26199894

  2. Executive function in preschool children prenatally exposed to methadone or buprenorphine.

    PubMed

    Konijnenberg, Carolien; Melinder, Annika

    2015-01-01

    Although an increasing number of children are born with prenatal methadone or buprenorphine exposure, little is still known about the potential long-term effects of these opioids. The aim of this study was to investigate executive function (EF) in children of women in opioid maintenance therapy (OMT). A total of 66 children (aged 48-57 months) participated in the study, 35 of which had histories of prenatal methadone or buprenorphine exposure. EF was measured using a battery of neuropsychological tests and the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Results showed that children of women in OMT perform lower on tasks of short-term memory and inhibition compared to nonexposed children, which was mainly associated with lower maternal education and employment rate. The OMT group scored significantly lower on all EF tasks compared to the nonexposed group, although scores fell within the average range on all measures. The development of these children should be monitored to assess for the possible problem behaviors and to promote optimal outcomes. PMID:25354916

  3. Respiratory effects of buprenorphine/naloxone alone and in combination with diazepam in naive and tolerant rats.

    PubMed

    Cohier, Camille; Chevillard, Lucie; Risède, Patricia; Roussel, Olivier; Mégarbane, Bruno

    2014-07-15

    Respiratory depression has been attributed to buprenorphine (BUP) misuse or combination with benzodiazepines. BUP/naloxone (NLX) has been marketed as maintenance treatment, aiming at preventing opiate addicts from self-injecting crushed pills. However, to date, BUP/NLX benefits in comparison to BUP alone remain debated. We investigated the plethysmography effects of BUP/NLX in comparison to BUP/solvent administered by intravenous route in naive and BUP-tolerant Sprague-Dawley rats, and in combination with diazepam (DZP) or its solvent. In naive rats, BUP/NLX in comparison to BUP significantly increased respiratory frequency (f, P<0.05) without altering minute volume (VE). In combination to DZP, BUP/NLX significantly increased expiratory time (P<0.01) and decreased f (P<0.01), tidal volume (VT, P<0.001), and VE (P<0.001) while BUP only decreased VT (P<0.5). In BUP-tolerant rats, no significant differences in respiratory effects were observed between BUP/NLX and BUP. In contrast, in combination to DZP, BUP/NLX did not significantly alter the plethysmography parameters, while BUP increased inspiratory time (P<0.001) and decreased f (P<0.01) and VE (P<0.001). In conclusion, differences in respiratory effects between BUP/NLX and BUP are only significant in combination with DZP, with increased depression in naive rats but reduced depression in BUP-tolerant rats. However, BUP/NLX benefits in humans remain to be determined. PMID:24769261

  4. Analgesic efficacy of buprenorphine in the presence of high levels of SDF-1α/CXCL12 in the brain.

    PubMed

    Benamar, Khalid; Palma, Jonathan; Cowan, Alan; Geller, Ellen B; Adler, Martin W

    2011-04-01

    Although morphine is often the best option for treating acute and chronic severe pain, its analgesic activity can be blocked in situations in which there are elevated levels of chemokines. Indeed, recently we have shown that elevated brain levels of the chemokine stromal cell-derived growth factor-1alpha (SDF-1α/CXCL12, the ligand of the HIV co-receptor CXCR4) diminish the antinociceptive effect of morphine. The purpose of the present study was to investigate whether such an effect is restricted to morphine or extends to other opioid medications such as buprenorphine. A sterilized stainless-steel C313G guide cannula was implanted into the periaqueductal grey (PAG), a brain region critical to the processing of pain signals, and a primary site of action of many analgesic compounds. The cold-water (-3°C) tail-flick test (CWT) was used to measure antinociception. Rats were pretreated with SDF-1α/CXCL12 administered into the PAG, and the antinociceptive actions of buprenorphine were measured. Direct infusion of SDF-1α/CXCL12 into the PAG failed to alter the antinociceptive action of buprenorphine. The presence of SDF-1α/CXCL12 in the PAG differentially alters the antinociceptive function of opioid medications. While it was able to diminish the antinociception induced by morphine (Adler et al., 2006), SDF-1α/CXCL12 did not affect the buprenorphine-induced antinociception. Buprenorphine appears to be more effective in the presence of high levels of SDF-1α/CXCL12 in the brain (which frequently occurs during neuroinflammatory conditions). PMID:21112161

  5. Experiences from a Community Based Substance Use Treatment Centre in an Urban Resettlement Colony in India

    PubMed Central

    Balhara, Yatan Pal Singh; Ranjan, Rajeev; Dhawan, Anju; Yadav, Deepak

    2014-01-01

    Background. There are limited community based treatment services for drug dependence in India. Rural areas and urban resettlement colonies are in particular deficient in such services. Aims. The current study aimed at preliminary assessment of substance use disorder management services at a community based substance use treatment clinic in an urban resettlement colony. Methods. The study was carried out at community based substance use treatment centre in a resettlement colony in India. The records of the centre were chart reviewed. Results. A total of 754 patients were registered at the clinic during the study period. Heroin was the primary drug of abuse for 63% of the patients. The mean duration of follow-up for the patients with opioid and alcohol dependence was 13.47 (SD ± 10.37; range 0–39) months. A total of 220 patients of opioid dependence were prescribed substation or abstinence directed therapy. Buprenorphine (87), slow release oral morphine (SROM) (16), and dextropropoxyphene (98) were used for opioid substitution. Conclusion. It is possible to deliver substance use disorder treatment services in community setting. There is a need to develop area specific community based treatment services for substance abuse in socially disadvantaged populations such as urban resettlement colonies. PMID:25431739

  6. Roles of μ-Opioid Receptors and Nociceptin/Orphanin FQ Peptide Receptors in Buprenorphine-Induced Physiological Responses in Primates

    PubMed Central

    Cremeans, Colette M.; Gruley, Erin; Kyle, Donald J.

    2012-01-01

    Buprenorphine is known as a μ-opioid peptide (MOP) receptor agonist, but its antinociception is compromised by the activation of nociceptin/orphanin FQ peptide (NOP) receptors in rodents. The aim of this study was to investigate the roles of MOP and NOP receptors in regulating buprenorphine-induced physiological responses in primates (rhesus monkeys). The effects of MOP antagonist (naltrexone), NOP antagonist [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397)], and NOP agonists [(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5] decan-4-one (Ro 64-6198) and 3-endo-8-[bis(2-methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510)] on buprenorphine were studied in three functional assays for measuring analgesia, respiratory depression, and itch in primates. Over the dose range of 0.01 to 0.1 mg/kg, buprenorphine dose-dependently produced antinociception, respiratory depression, and itch/scratching responses, and there was a ceiling effect at higher doses (0.1–1 mg/kg). Naltrexone (0.03 mg/kg) produced similar degrees of rightward shifts of buprenorphine's dose-response curves for all three endpoints. Mean pKB values of naltrexone (8.1–8.3) confirmed that MOP receptors mediated mainly buprenorphine-induced antinociception, respiratory depression, and itch/scratching. In contrast, J-113397 (0.1 mg/kg) did not change buprenorphine-induced physiological responses, indicating that there were no functional NOP receptors in buprenorphine-induced effects. More importantly, both NOP agonists, Ro 64-6198 and SCH 221510, enhanced buprenorphine-induced antinociception without respiratory depression and itch/ scratching. The dose-addition analysis revealed that buprenorphine in combination with the NOP agonist synergistically produced antinociceptive effects. These findings provided functional evidence that the activation of NOP receptors did not

  7. Buprenorphine detection in urine using liquid chromatography-high-resolution mass spectrometry: comparison with cloned enzyme donor immunoassay (ThermoFisher) and homogeneous enzyme immunoassay (immunalysis).

    PubMed

    Belsey, Sarah L; Couchman, Lewis; Flanagan, Robert J

    2014-09-01

    A sensitive liquid chromatographic-high-resolution mass spectrometric (LC-HR-MS) assay for buprenorphine and its urinary metabolites has been developed that requires minimal sample preparation. The results obtained have been compared with those given by (i) cloned enzyme donor immunoassay (CEDIA) and (ii) homogeneous enzyme immunoassay (HEIA) in the analysis of patient urines submitted for buprenorphine analysis. Centrifuged urine (100 µL) was diluted with internal standard solution (25 µL) + LC eluent (875 µL), and 50 µL of the prepared sample were analyzed (Accucore Phenyl-Hexyl column). MS detection was in alternating positive and negative mode using heated electrospray ionization (ThermoFisher Q Exactive). Intra- and inter-assay accuracy and precision were 104-128 and <11%, respectively, at 5 µg/L. Limits of detection were 1.3 µg/L (buprenorphine, norbuprenorphine and buprenorphine glucuronide) and 2.5 µg/L (norbuprenorphine glucuronide). Immunoassay sensitivity and selectivity were 97 and 100% (HEIA) and 99 and 84% (CEDIA), respectively, compared with LC-HR-MS. In 120 patient urines, norbuprenorphine glucuronide was easily the most abundant analyte except when adulteration with buprenorphine had occurred. The median immunoreactive buprenorphine species present (unhydrolysed urine) were 7.5 and 13% for HEIA and CEDIA, respectively. However, codeine, dihydrocodeine, morphine and morphine-3-glucuronide did not interfere in the HEIA assay. PMID:24925983

  8. P-15 small peptide bone graft substitute in the treatment of non-unions and delayed union. A pilot clinical trial

    PubMed Central

    Orozco, Rafael; Villar, Jose Luis; Arrizabalaga, Federico

    2006-01-01

    Treatment of non-unions and delayed unions often requires osteogenic material. Recently, a biomimetic bone matrix that simulates the cellular environment of hard tissue, identified as P-15, was introduced to the orthopaedic community. A total of 22 patients with mal-union or delayed union fractures was treated from June 2000 to October 2003 with P15- bone graft substitute (P15-BGS) in the site of fracture and mostly with internal fixation. Patients were examined by independent radiographic analysis. Assessment criteria included time elapsed until bone bridging and time to full consolidation. In addition, histological assessment of the callus was done at the time of recovery of metal implants in five patients. Full consolidation was achieved in 90% (20 out of 22) of the patients treated with P15-BGS. The average time for full consolidation was 4.2 months. Histological assessment of the fracture callus in five of the patients confirmed the positive clinical and radiographic results. P15-BGS appears to offer a safe, economical and clinically useful alternative to autograft in the repair of ununited fractures. These results compare favourably with those in the published literature as an alternative to autograft. PMID:16761146

  9. Cross-reactivity of the CEDIA buprenorphine assay in drugs-of-abuse screening: influence of dose and metabolites of opioids

    PubMed Central

    Berg, Jon Andsnes; Schjøtt, Jan; Fossan, Kjell O; Riedel, Bettina

    2015-01-01

    Purpose The cloned enzyme donor immunoassay (CEDIA) for buprenorphine is applied for both urine drugs-of-abuse screening and compliance monitoring. Sensitivity, specificity, and optimal cutoff of this assay have differed between studies. This may indicate that cross-reactivity has to be taken into account during assay evaluation. We therefore investigated the performance of the CEDIA buprenorphine assay for use in our patient population and explored the impact of cross-reactivity on assay accuracy. Methods The CEDIA buprenorphine assay and high-performance liquid chromatography–tandem mass spectrometry were employed to analyze drugs-of-abuse in urine samples from a healthy drug-naïve male volunteer after intake of two tablets of a prescription drug containing 400 mg paracetamol +30 mg codeine phosphate, and in urine samples (n=2,272) from drug-addicted patients. Receiver operating characteristic analyses were performed to express the diagnostic accuracy of the CEDIA buprenorphine assay. Results CEDIA buprenorphine was positive in one urine sample from the drug-naïve person after intake of the prescription drug. Twenty-five (1.1%) of the patient urine samples were positive for buprenorphine by CEDIA, but negative by high-performance liquid chromatography–tandem mass spectrometry. Codeine, morphine, and their respective metabolites were prevalent in samples that were false positive for buprenorphine. The specificity of the CEDIA buprenorphine assay increased to 99.7% when the cutoff was increased from 5 ng/mL to 10 ng/mL. Conclusion Intake of a therapeutic dose of codeine can yield a false-positive CEDIA buprenorphine result. Additive effects from metabolites of codeine contribute to cross-reactivity in concentrations much lower than listed in the manufacturer’s cross-reactivity guide. Raising the cutoff from 5 ng/mL to 10 ng/mL increased the diagnostic accuracy. Clinicians should be informed about the risk of false-positive results with the CEDIA

  10. Treating tobacco use disorder in pregnant women in medication-assisted treatment for an opioid use disorder: a systematic review.

    PubMed

    Akerman, Sarah C; Brunette, Mary F; Green, Alan I; Goodman, Daisy J; Blunt, Heather B; Heil, Sarah H

    2015-05-01

    Smoking is associated with adverse effects on pregnancy and fetal development, yet 88-95% of pregnant women in medication-assisted treatment for an opioid use disorder smoke cigarettes. This review summarizes existing knowledge about smoking cessation treatments for pregnant women on buprenorphine or methadone, the two forms of medication-assisted treatment for opioid use disorder indicated for prenatal use. We performed a systematic review of the literature using indexed terms and key words to capture the concepts of smoking, pregnancy, and opioid substitution and found that only three studies met search criteria. Contingency management, an incentive based treatment, was the most promising intervention: 31% of participants achieved abstinence within the 12-week study period, compared to 0% in a non-contingent behavior incentive group and a group receiving usual care. Two studies of brief behavioral interventions resulted in reductions in smoking but not cessation. Given the growing number of pregnant women in medication-assisted treatment for an opioid use disorder and the negative consequences of smoking on pregnancy, further research is needed to develop and test effective cessation strategies for this group. PMID:25592332

  11. The in vivo glucuronidation of buprenorphine and norbuprenorphine determined by liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Huang, Wei; Moody, David E; McCance-Katz, Elinore F

    2006-04-01

    The opioid partial agonist medication, buprenorphine (BUP), and its primary metabolite, norbuprenorphine (NBUP), are extensively glucuronidated. Sensitive analytical methods that include determination of buprenorphine-3-glucuronide (BUPG) and norbuprenorphine-3-glucuronide (NBUPG) are needed to more fully understand the metabolism and pharmacokinetics of buprenorphine. A method has now been developed that uses solid-phase extraction followed by liquid chromatography-electrospray ionization-tandem mass spectrometry. BUP-d4, NBUP-d3, and morphine-3-glucuronide-d3 were used as internal standards. The lower limit of quantitation was 0.1 and 0.5 ng/mL for each of the analytes in 1-mL of human plasma and urine, respectively, except for NBUP in urine in which it was 2.5 ng/mL. The analytes were stable under the following conditions: plasma and urine at room temperature, up to 20 hours; plasma and urine at -20 degrees C for 119 and 85 days, respectively; plasma freeze-thaw, up to 3 cycles; processed sample, up to 96 hours at -20 degrees C and up to 48 hours on the autosampler; stock solutions at room temperature and at -20 degrees C, up to 6 hours and 128 days, respectively. In plasma collected from 5 subjects on maintenance daily sublingual doses of 16 mg BUP and 4 mg naloxone, respective 0- to 24-hour areas under the curve were 32, 88, 26, and 316 ng/mL x h for BUP, NBUP, BUPG, and NBUPG. In urine samples respective percent of daily dose excreted in the 24-hour urine were 0.014%, 1.89%, 1.01%, and 7.76%. This method allowed us to determine that NBUPG is a major metabolite present in plasma and urine of BUP. Because urinary elimination is limited ( approximately 11% of daily dose), the role of NBUPG in total clearance of buprenorphine is not yet known. PMID:16628138

  12. A comparative study on postoperative pain relief in laparoscopic cholecystectomy: Intraperitoneal bupivacaine versus combination of bupivacaine and buprenorphine

    PubMed Central

    Khurana, Sandeep; Garg, Kamakshi; Grewal, Anju; Kaul, Tej K.; Bose, Abhishek

    2016-01-01

    Context: To assess the analgesic efficacy of the combination of bupivacaine and buprenorphine in alleviating postoperative pain following laparoscopic cholecystectomy. Aims: Laparoscopic cholecystectomy is comparatively advantageous as it offers less pain in the postoperative period and requires a shorter hospital stay. There are only a few studies performed to evaluate the analgesic efficacy of intraperitoneal instillation of buprenorphine and bupivacaine during laparoscopic cholecystectomy. Settings and Design: The present research is a randomized, double-blind controlled study conducted in the Department of Anaesthesiology, Dayanand Medical College and Hospital Ludhiana, Punjab after formal ethical approval from Hospital's Ethics Committee. Subjects and Methods: This study analyzed 90 adults admitted for elective laparoscopic cholecystectomy. After the procedure, subjects were divided into three equal groups to conduct the study. Three Groups A, B, and C had intraperitoneal instillation of the 25 ml of physiological saline (0.9% normal saline), 0.25% of bupivacaine, 0.25% bupivacaine, and 0.3 mg buprenorphine, respectively. Necessary vitals were monitored and recorded. Visual analog scale (VAS) and verbal rating scale (VRS) scores were recorded and analyzed systematically. Statistical Analysis Used: All observations were analyzed using analysis of variance and Student's t-test. Results: The mean pain scores were highest in Group A compared to Group B and Group C. Mean VAS and VRS scores were highest in Group C comparatively and lowest in Group A. Conclusion: Combination of buprenorphine and bupivacaine intraperitoneally is comparatively more effective in relieving postoperative pain in comparison to intraperitoneal instillation of bupivacaine alone for postoperative pain management after laparoscopic cholecystectomy. PMID:26957685

  13. Validation and Application of a Method for the Determination of Buprenorphine, Norbuprenorphine, and Their Glucuronide Conjugates in Human Meconium

    PubMed Central

    Kacinko, Sherri L.; Shakleya, Diaa M.; Huestis, Marilyn A.

    2009-01-01

    A novel liquid chromatography tandem mass spectrometry method for quantification of buprenorphine, norbuprenorphine, and glucuronidated conjugates was developed and validated. Analytes were extracted from meconium using buffer, concentrated by solid-phase extraction and quantified within 13.5 min. In order to determine free and total concentrations, specimens were analyzed with and without enzyme hydrolysis. Calibration was achieved by linear regression with a 1/x weighting factor and deuterated internal standards. All analytes were linear from 20 to 2000 ng/g with a correlation of determination of >0.98. Accuracy was ≥85.7% with intra-assay and interassay imprecision ≤13.9 and 12.4%, respectively. There was no interference from 70 licit and illicit drugs and metabolites. Buffer extraction followed by SPE yielded recoveries of ≥85.0%. There was suppression of ionization by the polar matrix; however, this did not interfere with sensitivity or analyte quantification due to inclusion of deuterated internal standards. Analytes were stable on the autosampler, at room temperature, at 4 °C, and when exposed to three freeze/thaw cycles. This sensitive and specific method can be used to monitor in utero buprenorphine exposure and to evaluate correlations, if any, between buprenorphine exposure and neonatal outcomes. PMID:18044957

  14. Buprenorphine provides better anaesthetic conditions than butorphanol for field castration in ponies: results of a randomised clinical trial.

    PubMed

    Rigotti, C; De Vries, A; Taylor, P M

    A prospective, randomised, blinded, clinical trial in 47 ponies compared butorphanol and buprenorphine administered intravenously with detomidine prior to castration under anaesthesia. Detomidine 12 μg/kg intravenously was followed by butorphanol 25 μg/kg (BUT) or buprenorphine 5 μg/kg (BUP) before induction of anaesthesia with intravenous ketamine and diazepam. Quality of sedation, induction and recovery from anaesthesia, response to tactile stimulation, and surgical conditions were scored. If anaesthesia was inadequate 'rescue' was given with intravenous ketamine (maximum three doses) followed by intravenous thiopental and detomidine. Time from induction to first rescue, total ketamine dose and number of rescues were recorded. Postoperative locomotor activity was scored and abnormal behaviour noted. Simple descriptive scales were used for all scoring. Data were analysed using two-way analysis of variance, t tests, Mann-Whitney or Fisher's exact tests as appropriate; P<0.05 was considered statistically significant. Cryptorchid animals did not undergo surgery, but castration was successfully completed in 18 BUT and 20 BUP. More incremental ketamine (P=0.0310) and more rescue drugs (P=0.0165) were required in BUT and more postoperative locomotor activity occurred in BUP (P=0.0001). There were no other differences between groups. Both opioids were suitable for premedication prior to castration but buprenorphine appeared to provide better intraoperative analgesia. PMID:25262056

  15. Simultaneous determination of buprenorphine, norbuprenorphine and naloxone in human plasma by liquid chromatography/tandem mass spectrometry.

    PubMed

    Liu, Yongzhen; Li, Xiaohua; Xu, Allan; Nasser, Azmi F; Heidbreder, Christian

    2016-02-20

    A simple, sensitive and rapid liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for simultaneous quantification of naloxone, buprenorphine and its metabolite norbuprenorphine in human plasma. Human plasma samples were extracted using a single step liquid-liquid extraction, and then separated on an Imtakt Unison UK-C18 column (2.1×50mm, 3μm) using alkaline mobile phases with gradient elution. All of the analytes were detected in positive ion mode using multiple reaction monitoring (MRM). The method was validated and the specificity, linearity, lower limit of quantitation, precision, accuracy, recoveries and stability were determined. The linear range was 20-10000pg/mL for buprenorphine and norbuprenorphine; and 1-500pg/mL for naloxone. The correlation coefficient (R(2)) values for all three analytes were ≥0.995. The precision and accuracy for intra-day and inter-day were <11.0%. The recoveries were >63% and matrix effects were tracked by the deuterated internal standards (IS) with the IS-normalized matrix factor ranging from 0.96 to 1.33 for all three analytes. The validated method was successfully applied in a clinical pharmacokinetic study with low dose administration of sublingual buprenorphine and naloxone. PMID:26730511

  16. Biologic and synthetic skin substitutes: An overview

    PubMed Central

    Halim, Ahmad Sukari; Khoo, Teng Lye; Mohd. Yussof, Shah Jumaat

    2010-01-01

    The current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing. PMID:21321652

  17. Patients' Beliefs About Medications are Associated with Stated Preference for Methadone, Buprenorphine, Naltrexone, or no Medication-Assisted Therapy Following Inpatient Opioid Detoxification.

    PubMed

    Uebelacker, Lisa A; Bailey, Genie; Herman, Debra; Anderson, Bradley; Stein, Michael

    2016-07-01

    Subsequent to initial opioid detoxification, people with opioid use disorder are typically advised to engage in follow-up treatment to prevent relapse. Medication-assisted treatments (MATs) - i.e., the opioid agonist methadone (MMT) or partial agonist/antagonist, buprenorphine/naltrexone (BUP) -- are the maintenance treatment options with the best research support for positive outcomes. A third MAT, injectable extended-release naltrexone (XR-NTX), was approved by the FDA for opioid dependence in 2010 and shows promise. However, relatively few eligible patients choose to initiate one of these MATs following initial detoxification treatment. Consistent with the health belief model, we hypothesized that beliefs about 1) efficacy of each MAT; 2) safety of each MAT; and 3) perceived consistency with being drug-free would predict stated patient preferences for a particular MAT or for no MAT. We also hypothesized that perceived structural barriers (e.g., time, transportation) would decrease the likelihood of stating a preference for a given MAT. To assess these hypotheses, we surveyed 372 people undergoing inpatient opioid detoxification treatment. Results supported hypotheses for all 3 sets of patient beliefs, with the patient group stating that they preferred a particular MAT having significantly more positive beliefs about that MAT relative to other groups (p<.001). The group that preferred "no MAT" had the most negative beliefs about all MATs. Perceived structural barriers were not related to stated preferences, except that people who preferred BUP were more likely to endorse barriers to MMT than any of the other 3 groups. Notably, a relatively high proportion (32%) of participants were most interested in XR-NTX despite a lack of prior experience with this medication. These results suggest that efforts to increase MAT enrollment following detoxification might benefit from including patient beliefs as one set of factors to assess and target for change. PMID:27211996

  18. Borate substituted ettringites

    SciTech Connect

    Csetenyi, L.J.; Glasser, F.P.

    1993-12-31

    The setting of cement is adversely affected by soluble borates. To reduce interference, the extent to which borate can be insolubilized has been investigated. One specific mechanism of insolubilization is by inclusion into ettringite. Ettringite, Ca{sub 6}Al{sub 2}(SO{sub 4}){sub 3}(OH){sub 12}{center_dot}26H{sub 2}O, is a normal and stable constituent of Portland cement. It has an open but non-zeolitic framework. Borate can substitute partially or fully for sulfate. Formation conditions, solubility and stability of borate ettringites, Ca{sub 6}Al{sub 2}(BO{sub 4}){sub 2-4}(OH,O){sub 12}{center_dot}26H{sub 2}O, are characterized using XRD, IR, DTA, and SEM. The potential durability of borate ettringites in a repository environment have been assessed by exposing it to Na-sulfate and Na-carbonate attack at different concentrations. Ion exchange occurs; back substitution of borate by sulfate is incomplete; high carbonate concentrations can, however, decompose borate ettringite. On heat treatment up to 85{degrees}C the crystalline morphology and the OH arrangement of the structure are altered, but the X-ray powder pattern, and hence its structural framework are largely unaffected. It is concluded that ettringite has potential to reduce the solubility of borate.

  19. Nucleophilic Aromatic Substitution.

    ERIC Educational Resources Information Center

    Avila, Walter B.; And Others

    1990-01-01

    Described is a microscale organic chemistry experiment which demonstrates one feasible route in preparing ortho-substituted benzoic acids and provides an example of nucleophilic aromatic substitution chemistry. Experimental procedures and instructor notes for this activity are provided. (CW)

  20. National and State Treatment Need and Capacity for Opioid Agonist Medication-Assisted Treatment

    PubMed Central

    Campopiano, Melinda; Baldwin, Grant; McCance-Katz, Elinore

    2015-01-01

    Objectives. We estimated national and state trends in opioid agonist medication-assisted treatment (OA-MAT) need and capacity to identify gaps and inform policy decisions. Methods. We generated national and state rates of past-year opioid abuse or dependence, maximum potential buprenorphine treatment capacity, number of patients receiving methadone from opioid treatment programs (OTPs), and the percentage of OTPs operating at 80% capacity or more using Substance Abuse and Mental Health Services Administration data. Results. Nationally, in 2012, the rate of opioid abuse or dependence was 891.8 per 100 000 people aged 12 years or older compared with national rates of maximum potential buprenorphine treatment capacity and patients receiving methadone in OTPs of, respectively, 420.3 and 119.9. Among states and the District of Columbia, 96% had opioid abuse or dependence rates higher than their buprenorphine treatment capacity rates; 37% had a gap of at least 5 per 1000 people. Thirty-eight states (77.6%) reported at least 75% of their OTPs were operating at 80% capacity or more. Conclusions. Significant gaps between treatment need and capacity exist at the state and national levels. Strategies to increase the number of OA-MAT providers are needed. PMID:26066931

  1. The effect of statutory limitations on the authority of substitute decision makers on the care of patients in the intensive care unit: case examples and review of state laws affecting withdrawing or withholding life-sustaining treatment.

    PubMed

    Venkat, Arvind; Becker, Julianna

    2014-01-01

    While the ethics and critical care literature is replete with discussion of medical futility and the ethics of end-of-life care decisions in the intensive care unit, little attention is paid to the effect of statutory limitations on the authority of substitute decision makers during the course of treatment of patients in the critical care setting. In many jurisdictions, a clear distinction is made between the authority of a health care power of attorney, who is legally designated by a competent adult to make decisions regarding withholding or withdrawing life-sustaining treatment, and of next-of-kin, who are limited in this regard. However, next-of-kin are often relied upon to consent to necessary procedures to advance a patient's medical care. When conflicts arise between critical care physicians and family members regarding projected patient outcome and functional status, these statutory limitations on decision-making authority by next of kin can cause paralysis in the medical care of severely ill patients, leading to practical and ethical impasses. In this article, we will provide case examples of how statutory limitations on substitute decision making authority for next of kin can impede the care of patients. We will also review the varying jurisdictional limitations on the authority of substitute decision makers and explore their implications for patient care in the critical care setting. Finally, we will review possible ethical and legal solutions to resolve these impasses. PMID:22257784

  2. THE TREATMENT OF ALCOHOL AND OPIOID DEPENDENCE IN PREGNANT WOMEN

    PubMed Central

    Heberlein, Annemarie; Leggio, Lorenzo; Stichtenoth, Dirk; Thomas, Hillemacher

    2016-01-01

    Purpose of the review This article addresses the question of “best treatment options,” which clinicians face when treating pregnant women with alcohol and/or opioid dependence. Recent findings Alcohol Studies show that alcohol consumption is associated with fetal abnormalities and long-term cognitive problems depending on amount consumed, drinking pattern, and time of gestation. Screening and evaluation of specific interventions are important to reduce alcohol consumption during pregnancy and associated problems in infants. Opioids Withdrawal-induced fetal distress and the risk of relapse are the primary reasons why opioid detoxification is only recommended in the second or third trimesters and only in those pregnant women who refuse opioid maintenance therapy (OMT). Methadone is the most established treatment of pregnant opioid-dependent women, but recent investigations suggest that substitution with buprenorphine may have advantages over methadone in terms of neonatal abstinence syndrome (NAS). Promising results have been also reported for slow-release oral methadone and the heroin equivalent diamorphin. Summary Data regarding the pharmacological treatment of alcohol abuse and/or dependence is limited in pregnant women. So far, benzodiazepines seem to be the most recommendable option for managing alcohol withdrawal, and psychosocial interventions succeed in reducing alcohol consumption or in maintaining abstinence in alcohol-dependent pregnant women. Recent data, albeit preliminary, support the use of naltrexone in the treatment of alcohol-dependent pregnant women. Regarding opioid dependence meta-analyses do not clearly support the superiority of one substitute over the other during pregnancy owing to the presence of interfering factors (such as illicit drug use) in the studies conducted. Current results suggest that factors like the health status of the mother, the need for additional medications (e.g. treatment for HIV), comorbid drug dependence, and

  3. Substitute Addiction: A Concern for Researchers and Practitioners

    ERIC Educational Resources Information Center

    Sussman, Steve; Black, David S.

    2008-01-01

    An understanding of the role of substitute addictions remains unclear. This article examines the range and possible reward functions of substitute addictions. We suggest that prevention education and treatment need to take into account substitute addictions as an influential aspect of recovery. Research is needed to better understand the…

  4. 40 CFR 721.8780 - Substituted pyridine azo substituted phenyl.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Substituted pyridine azo substituted... Specific Chemical Substances § 721.8780 Substituted pyridine azo substituted phenyl. (a) Chemical substance... substituted pyridine azo substituted phenyl (PMNs P-96-767 and P-96-773) are subject to reporting under...

  5. 40 CFR 721.8780 - Substituted pyridine azo substituted phenyl.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted pyridine azo substituted... Specific Chemical Substances § 721.8780 Substituted pyridine azo substituted phenyl. (a) Chemical substance... substituted pyridine azo substituted phenyl (PMNs P-96-767 and P-96-773) are subject to reporting under...

  6. 40 CFR 721.8780 - Substituted pyridine azo substituted phenyl.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Substituted pyridine azo substituted... Specific Chemical Substances § 721.8780 Substituted pyridine azo substituted phenyl. (a) Chemical substance... substituted pyridine azo substituted phenyl (PMNs P-96-767 and P-96-773) are subject to reporting under...

  7. 40 CFR 721.8780 - Substituted pyridine azo substituted phenyl.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Substituted pyridine azo substituted... Specific Chemical Substances § 721.8780 Substituted pyridine azo substituted phenyl. (a) Chemical substance... substituted pyridine azo substituted phenyl (PMNs P-96-767 and P-96-773) are subject to reporting under...

  8. 40 CFR 721.8780 - Substituted pyridine azo substituted phenyl.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Substituted pyridine azo substituted... Specific Chemical Substances § 721.8780 Substituted pyridine azo substituted phenyl. (a) Chemical substance... substituted pyridine azo substituted phenyl (PMNs P-96-767 and P-96-773) are subject to reporting under...

  9. Faculty Development in Small-Group Teaching Skills Associated with a Training Course on Office-Based Treatment of Opioid Dependence

    ERIC Educational Resources Information Center

    Wong, Jeffrey G.; Holmboe, Eric S.; Becker, William C.; Fiellin, David A.; Jara, Gail B.; Martin, Judith

    2005-01-01

    The Drug Addiction Treatment Act of 2000 (DATA-2000) allows qualified physicians to treat opioid-dependent patients with schedule III-V medications, such as buprenorphine, in practices separate from licensed, accredited opioid treatment programs. Physicians may attain this qualification by completing 8-hours of training in treating opioid…

  10. Managing severe cancer pain: the role of transdermal buprenorphine: a systematic review

    PubMed Central

    Deandrea, S; Corli, O; Moschetti, I; Apolone, G

    2009-01-01

    Pain is a frequent and important symptom in cancer patients. Among the available strong opioids, transdermal buprenorphine has been licensed in Europe since 2002, and results from a few clinical studies suggest that it may be a good alternative to the other oral or transdermal opioids. To assess the best available evidence on its efficacy and safety, we carried out a systematic literature review with the aim of pooling relevant studies. We identified 19 eligible papers describing 12 clinical studies (6 randomized controlled trials and 6 observational prospective studies), including a total of about 5000 cancer patients. Given the poor quality of reports and the heterogeneity of methods and outcomes, pooling was not feasible as the type of data was not appropriate for combining the results statistically. A meta-analysis based on individual data is ongoing in the context of the Cochrane Collaboration. In conclusion, although the narrative appraisal of each study suggests a positive risk benefit profile, well designed and statistically powered controlled clinical trials are needed to confirm this preliminary evidence. PMID:19774212

  11. A statistical experimental design approach to evaluate the influence of various penetration enhancers on transdermal drug delivery of buprenorphine

    PubMed Central

    Taghizadeh, S.Mojtaba; Moghimi-Ardakani, Ali; Mohamadnia, Fatemeh

    2014-01-01

    A series of drug-in-adhesive transdermal drug delivery systems (patch) with different chemical penetration enhancers were designed to deliver drug through the skin as a site of application. The objective of our effort was to study the influence of various chemical penetration enhancers on skin permeation rate and adhesion properties of a transdermal drug delivery system using Box–Behnken experimental design. The response surface methodology based on a three-level, three-variable Box–Behnken design was used to evaluate the interactive effects on dependent variables including, the rate of skin permeation and adhesion properties, namely peel strength and tack value. Levulinic acid, lauryl alcohol, and Tween 80 were used as penetration enhancers (patch formulations, containing 0–8% of each chemical penetration enhancer). Buprenorphine was used as a model penetrant drug. The results showed that incorporation of 20% chemical penetration enhancer into the mixture led to maximum skin permeation flux of buprenorphine from abdominal rat skin while the adhesion properties decreased. Also that skin flux in presence of levulinic acid (1.594 μg/cm2 h) was higher than Tween 80 (1.473 μg/cm2 h) and lauryl alcohol (0.843 μg/cm2 h), and in mixing these enhancers together, an additional effect was observed. Moreover, it was found that each enhancer increased the tack value, while levulinic acid and lauryl alcohol improved the peel strength but Tween 80 reduced it. These findings indicated that the best chemical skin penetration enhancer for buprenorphine patch was levulinic acid. Among the designed formulations, the one which contained 12% (wt/wt) enhancers exhibited the highest efficiency. PMID:25750749

  12. The effect of isoflurane anaesthesia and buprenorphine on the mouse grimace scale and behaviour in CBA and DBA/2 mice

    PubMed Central

    Miller, Amy; Kitson, Gemma; Skalkoyannis, Benjamin; Leach, Matthew

    2015-01-01

    Prevention or alleviation of pain in laboratory mice is a fundamental requirement of in vivo research. The mouse grimace scale (MGS) has the potential to be an effective and rapid means of assessing pain and analgesic efficacy in laboratory mice. Preliminary studies have demonstrated its potential utility for assessing pain in mouse models that involve potentially painful procedures. The next step in validation is to determine if the other procedures that are integral to these models, i.e. anaesthesia or analgesia, result in any changes in MGS score which would need to be taken into account when using this tool to assess post-procedural pain. Here, spontaneous behaviour and MGS data for CBA and DBA/2 mice were recorded at baseline and following either isoflurane anaesthesia (suitable to perform abdominal surgery) or 0.05 mg/kg s.c. buprenorphine. In line with previous studies, isoflurane anaesthesia alone had limited effects on the spontaneous behaviour in either strain of mice. Administration of buprenorphine resulted in increased periods of activity e.g. walking and chewing bedding in CBA mice. These effects were not demonstrated in DBA/2 mice. In comparison, buprenorphine alone had no impact on MGS score in either strain of mice, however DBA/2 mice showed a significant increase in MGS score following isoflurane anaesthesia. The presence of this increased MGS score must be taken into account when attempting to use the MGS to assess pain in DBA/2 mice. Further work should be carried out to establish the presence of this isoflurane effect in other strains and the potential influence of gender on the MGS. This further validation is necessary prior to implementation of this technique in clinical scenarios. PMID:26937061

  13. The pharmacological treatment of opioid addiction--a clinical perspective.

    PubMed

    Lobmaier, Philipp; Gossop, Michael; Waal, Helge; Bramness, Jorgen

    2010-06-01

    This article reviews the main pharmacotherapies that are currently being used to treat opioid addiction. Treatments include detoxification using tapered methadone, buprenorphine, adrenergic agonists such as clonidine and lofexidine, and forms of rapid detoxification. In opioid maintenance treatment (OMT), methadone is most widely used. OMT with buprenorphine, buprenorphine-naloxone combination, or other opioid agonists is also discussed. The use of the opioid antagonists naloxone (for the treatment of intoxication and overdose) and oral and sustained-release formulations of naltrexone (for relapse prevention) is also considered. Although recent advances in the neurobiology of addictions may lead to the development of new pharmacotherapies for the treatment of addictive disorders, a major challenge lies in delivering existing treatments more effectively. Pharmacotherapy of opioid addiction alone is usually insufficient, and a complete treatment should also include effective psychosocial support or other interventions. Combining pharmacotherapies with psychosocial support strategies that are tailored to meet the patients' needs represents the best way to treat opioid addiction effectively. PMID:20169438

  14. Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors

    PubMed Central

    Wang, Pei-Chen; Ho, Ing-Kang; Lee, Cynthia Wei-Sheng

    2015-01-01

    Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). Radioligand binding with tritium-labelled diprenorphine confirmed the expression of KOP receptors. Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. Acute application of the opioid receptor agonists— U-69593, DAMGO and nociceptin— inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. Buprenorphine, when applied acutely, inhibited AC activity to ~90% in cells expressing KOP+MOP+NOP receptors. Chronic exposure to buprenorphine induced concentration-dependent AC superactivation in cells expressing KOP+NOP receptors, and the level of this superactivation was even higher in KOP+MOP+NOP-expressing cells. Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. PMID:26153065

  15. Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors.

    PubMed

    Wang, Pei-Chen; Ho, Ing-Kang; Lee, Cynthia Wei-Sheng

    2015-11-01

    Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). Radioligand binding with tritium-labelled diprenorphine confirmed the expression of KOP receptors. Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. Buprenorphine, when applied acutely, inhibited AC activity to ~90% in cells expressing KOP+MOP+NOP receptors. Chronic exposure to buprenorphine induced concentration-dependent AC superactivation in cells expressing KOP+NOP receptors, and the level of this superactivation was even higher in KOP+MOP+NOP-expressing cells. Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. PMID:26153065

  16. Yohimbine Increases Opioid-Seeking Behavior in Heroin-Dependent, Buprenorphine-Maintained Individuals

    PubMed Central

    Greenwald, Mark K.; Lundahl, Leslie H.; Steinmiller, Caren L.

    2012-01-01

    Rationale In laboratory animals, the biological stressor yohimbine (α2-noradrenergic autoreceptor antagonist) promotes drug seeking. Human laboratory studies have demonstrated