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Sample records for buprenorphine substitution treatment

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Smoking cessation treatment among office-based buprenorphine treatment patients.

    PubMed

    Nahvi, Shadi; Blackstock, Oni; Sohler, Nancy L; Thompson, Devin; Cunningham, Chinazo O

    2014-08-01

    Opioid-dependent patients smoke at high rates, and office-based buprenorphine treatment provides an opportunity to offer cessation treatment. We examined tobacco use and smoking cessation treatment patterns among office-based buprenorphine treatment patients. We reviewed records of 319 patients treated with buprenorphine from 2005 to 2010. We examined smoking status, cessation medication prescriptions, and factors associated with receipt of cessation prescriptions. Mean age was 43.9 years; most were men (74.2%) and Hispanic (70.9%). At buprenorphine initiation, 21.9% had no documentation of smoking status, while 67.4% were current, 10% former, and 0.9% never smokers. Of current smokers, 16.8% received smoking cessation prescriptions. Patients retained (vs. not retained) in buprenorphine treatment were more likely to receive smoking cessation medications (26.3% vs. 11.2%, p<0.005). We observed a high tobacco use prevalence among buprenorphine patients, and limited provision of cessation treatment. This is a missed opportunity to impact the high tobacco use burden in opioid-dependent persons.

  7. 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

  8. Safety and tolerability of the switch from buprenorphine to buprenorphine/naloxone in an Italian addiction treatment centre.

    PubMed

    Stimolo, Clementina; Favero, Valentina Del; Zecchinato, Giancarlo; Buson, Roberto; Cusin, Davide; Pellachin, Patrizia; Simonetto, Pamela

    2010-01-01

    Abuse and misuse of pharmacological therapies represent major challenges in the healthcare system, particularly in patients receiving long-acting opioid drugs for the treatment of heroin or opioid addiction. The partial mu-opioid receptor agonist buprenorphine is used to treat opioid dependence, but diversion and misuse may occur. The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is associated with a reduced abuse potential, and has been shown to have promising efficacy for the treatment of opioid dependence. This observational study assessed the safety and efficacy of sublingual buprenorphine/naloxone combination therapy in patients with opioid dependence after therapeutic switch from buprenorphine monotherapy. A total of 94 patients being treated with buprenorphine monotherapy (average dose 8 mg/day; mean duration of therapy 840 days) were switched to buprenorphine/naloxone combination therapy. Patients were asked to rate their level of satisfaction with buprenorphine/naloxone combination treatment with respect to the management of withdrawal symptoms, and urinary toxicology tests were carried out before and 14 days after switching to combination therapy. Within 3 months, 75/94 patients (80%) previously treated with buprenorphine monotherapy had switched to sublingual buprenorphine/naloxone combination treatment (average dose buprenorphine 8 mg). Among patients receiving combination treatment for >3 months, 83% were receiving medication either weekly or fortnightly, based on the results of toxicological testing. A reduction in positive urinary toxicology tests was observed in patients within two weeks after being switched to combination treatment (before switch: 28, 9 and 2 positive tests for heroin, cocaine and heroin + cocaine, respectively vs 11, 3 and 1 after switch) and a total of 64 patients of the 75 who switched to combination therapy (85%) were satisfied with the management of

  9. I Heard About It From a Friend: Assessing Interest in Buprenorphine Treatment

    PubMed Central

    Fox, Aaron D.; Shah, Pooja A.; Sohler, Nancy L.; Lopez, Carolina M.; Starrels, Joanna L.; Cunningham, Chinazo O.

    2013-01-01

    Background In the United States, opioid abuse and dependence continue to be a growing problem, while treatment for opioid abuse and dependence remains fairly static. Buprenorphine treatment for opioid dependence is safe and effective but underutilized. Prior research has demonstrated low awareness and use of buprenorphine among marginalized groups. This study investigates syringe exchange participants’ awareness of, exposure to, and interest in buprenorphine treatment. Methods Syringe exchange participants were recruited from a mobile unit performing outreach to nine street-side sites in New York City. Computer-based interviews were conducted to determine: (1) opioid users’ awareness of, exposure to, and interest in buprenorphine treatment; and (2) the association between awareness or exposure and interest in buprenorphine treatment. Logistic regression models were used to examine the associations between awareness, direct exposure (i.e. having taken buprenorphine), or indirect exposure (i.e. knowing someone who had taken buprenorphine) and interest in buprenorphine treatment. Results Of 158 opioid users, 70% were aware of, 32% had direct exposure to, and 31% had indirect exposure to buprenorphine; 12% had been prescribed buprenorphine. Of 138 opioid users who had never been prescribed buprenorphine, 57% were interested in buprenorphine treatment. In multivariate models, indirect exposure was associated with interest in buprenorphine treatment (AOR = 2.65, 95% CI: 1.22 – 5.77), but awareness and direct exposure were not. Conclusions Syringe exchange participants were mostly aware of buprenorphine and interested in treatment, but few had actually been prescribed buprenorphine. Because indirect exposure to buprenorphine was associated with interest in treatment, future interventions could capitalize on indirect exposure, such as through peer mentorship, to address underutilization of buprenorphine treatment. PMID:24588297

  10. A Retrospective Evaluation of Inpatient Transfer from High-Dose Methadone to Buprenorphine Substitution Therapy.

    PubMed

    Oretti, Rossana

    2015-10-01

    The product license of buprenorphine/naloxone for opioid substitution therapy indicates reducing methadone concentrations to 30 mg or less per day for a minimum of 1 week before transferring patients to buprenorphine and no sooner than 24 hours after the last methadone dose, because of the risk of precipitated withdrawal and a corresponding high risk of relapse to opioid use. There are few studies describing high-dose methadone transfers. This retrospective case review assessed the feasibility of transferring patients on methadone doses above 30 mg/day to buprenorphine or buprenorphine/naloxone in the inpatient setting. Six of seven patients on 60-120 mg/day of methadone successfully completed the transfer, and four cases tested negative for opiates at long-term follow-up (6-15 months). This suggests that methadone transfer to buprenorphine can be performed rapidly without the need to taper methadone doses in patients indicated for a therapeutic switch. This small study is hypothesis-generating; larger, well-designed trials are needed to define a protocol that can be used routinely to improve and widen transfers to buprenorphine when indicated.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. Expanding treatment capacity for opioid dependence with office-based treatment with buprenorphine: National surveys of physicians.

    PubMed

    Arfken, Cynthia L; Johanson, Chris-Ellyn; di Menza, Salvatore; Schuster, Charles Roberts

    2010-09-01

    Office-based treatment of opioid dependence with buprenorphine has the potential to expand treatment capacity in the United States. However, nationally, little is known about the number, characteristics, and experiences of physicians certified to prescribe buprenorphine. Moreover, little is known about the impact of easing federal regulations on the number of patients a physician is allowed to treat concurrently. To address these questions, surveys of national samples of physicians certified to prescribe buprenorphine (2004-2008) were analyzed (N = 6,892). There has been a continual increase in the number of physicians certified to prescribe buprenorphine, increase in the mean number of patients treated by physicians, and decrease in patients turned away, coinciding temporally with easing of federal regulations. In addition, most physicians prescribed buprenorphine outside of traditional treatment settings. The U.S. experiment in expanding Schedule III-V medications for opioid dependence to physicians outside of formal substance abuse treatment facilities appears to have resulted in expanded capacity.

  19. 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

  20. Harm reduction agencies as a potential site for buprenorphine treatment

    PubMed Central

    Fox, Aaron D.; Chamberlain, Adam; Frost, Taeko; Cunningham, Chinazo O.

    2015-01-01

    Introduction Harm reduction agencies complement addiction treatment by providing diverse services that improve the health of people who use drugs. Buprenorphine maintenance treatment (BMT) is an effective opioid addiction treatment that may be provided from flexible settings, potentially including harm reduction agencies. This study investigated attitudes toward different potential sites for BMT (harm reduction agencies, general medical clinics, and drug treatment programs) among harm reduction clients. Methods Using computer-based interviews, participants indicated preferred potential site for BMT (harm reduction agency, drug treatment program, or general medical clinic), interest in BMT by potential site, motivation for treatment, and barriers to BMT. We used multivariable logistic regression to determine factors associated with harm reduction agency preference. Results Of 102 opioid users, the most preferred potential site for BMT was a harm reduction agency (51%), while fewer preferred general medical clinics (13%), drug treatment programs (12%) or were not interested in BMT (25%). In multivariable analysis, experiencing ≥ 1 barrier to BMT was strongly associated with preferring harm reduction agencies (aOR = 3.39, 95% CI: 1.00 – 11.43). Conclusion The potential to initiate BMT at harm reduction agencies is highly favorable among harm reduction clients, especially among those experiencing barriers to BMT. Offering BMT at harm reduction agencies could improve access to treatment, but studies are needed to determine safety and efficacy of this approach. PMID:25837290

  1. Top Manager Effects on Buprenorphine Adoption in Outpatient Substance Abuse Treatment Programs

    PubMed Central

    Friedmann, Peter D.; Jiang, Lan; Alexander, Jeffrey A.

    2013-01-01

    To examine the influence of top managers’ characteristics on the adoption of buprenorphine for opioid dependence among U.S. outpatient substance abuse treatment units, this investigation analyzed a cross-sectional national study of 547 such units in the 2004–2005 wave of the Drug Abuse Treatment System Survey. Administrators reported their demographics, training, and treatment orientation, as well as features of the unit and its pattern of use of buprenorphine. Nationally, 15.8% of programs offered any buprenorphine services. Greater adoption of buprenorphine correlated with directors’ younger age, longer tenure, male gender, and weaker endorsement of abstinence as the most important treatment goal. Availability of naltrexone and medical services also correlated positively with buprenorphine adoption. The authors conclude that leaders’ characteristics are related to the adoption of innovative practices in addiction treatment programs. Future work should examine whether leadership development for community addiction programs might speed up the diffusion of buprenorphine and other innovative, evidence-based practices. PMID:19296223

  2. 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

  3. 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

  4. Where Is Buprenorphine Dispensed to Treat Opioid Use Disorders? The Role of Private Offices, Opioid Treatment Programs, and Substance Abuse Treatment Facilities in Urban and Rural Counties

    PubMed Central

    STEIN, BRADLEY D; PACULA, ROSALIE LICCARDO; GORDON, ADAM J; BURNS, RACHEL M; LESLIE, DOUGLAS L; SORBERO, MARK J; BAUHOFF, SEBASTIAN; MANDELL, TODD W; DICK, ANDREW W

    2015-01-01

    Context Opioid use disorders are a significant public health problem. In 2002, the FDA approved buprenorphine as an opioid use disorder treatment when prescribed by waivered physicians who were limited to treating 30 patients at a time. In 2006, federal legislation raised this number to 100 patients. Although federal legislators are considering increasing these limits further and expanding prescribing privileges to nonphysicians, little information is available regarding the impact of such changes on buprenorphine use. We therefore examined the impact of the 2006 legislation—as well as the association between urban and rural waivered physicians, opioid treatment programs, and substance abuse treatment facilities—on buprenorphine distributed per capita over the past decade. Methods Using 2004-2011 state-level data on buprenorphine dispensed and county-level data on the number of buprenorphine-waivered physicians and substance abuse treatment facilities using buprenorphine, we estimated a multivariate ordinary least squares regression model with state fixed effects of a state’s annual total buprenorphine dispensed per capita as a function of the state’s number of buprenorphine providers. Findings The amount of buprenorphine dispensed has been increasing at a greater rate than the number of buprenorphine providers. The number of physicians waivered to treat 100 patients with buprenorphine in both rural and urban settings was significantly associated with increased amounts of buprenorphine dispensed per capita. There was no significant association in the growth of buprenorphine distributed and the number of physicians with 30-patient waivers. Conclusions The greater amounts of buprenorphine dispensed are consistent with the potentially greater use of opioid agonists for opioid use disorder treatment, though they also make their misuse more likely. The changes after the 2006 legislation suggest that policies focused on increasing the number of patients that a

  5. 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.

  6. Integrating buprenorphine treatment into a public healthcare system: the San Francisco Department of Public Health's office-based Buprenorphine Pilot Program.

    PubMed

    Hersh, David; Little, Sherri L; Gleghorn, Alice

    2011-01-01

    Despite well-documented efficacy, US physicians have been relatively slow to embrace the use of buprenorphine for the treatment of opioid dependence. In order to introduce and support the use of buprenorphine across the San Francisco Department of Public Health system of care, the Buprenorphine Pilot Program was initiated in 2003. Program treatment sites included a centralized buprenorphine induction clinic and program pharmacy, and three community-based treatment sites; two primary care clinics and a private dual diagnosis group practice. The target patient population consisted of opioid-dependent patients typically seen in an urban, public health setting, including individuals experiencing extreme poverty, homelessness/unstable housing, unemployment, polysubstance abuse/dependence, coexisting mental health disorders, and/or little psychosocial support. This program evaluation reviews patient characteristics, treatment retention, substance use over time, patient impressions, and provider practices for the 57 patients admitted between 9/1/03 and 8/31/05. At baseline, over 80% of patients were injecting heroin, over 40% were homeless, and over one-third were using cocaine. Outcomes included an overall one-year retention rate of 61%, a rapid and dramatic decline in opioid use, very positive patient impressions of the program and of buprenorphine, and significant shifts in provider practices over time.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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…

  16. 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. 

  17. 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

  18. 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…

  19. 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

  20. 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

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

    PubMed

    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.

  2. 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

    2014-12-17

    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.

  3. 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

  4. 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

  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. 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

  8. Characteristics of U.S. substance abuse treatment facilities adopting buprenorphine in its initial stage of availability.

    PubMed

    Koch, Alison L; Arfken, Cynthia L; Schuster, Charles R

    2006-07-27

    This study examined the adoption of buprenorphine for the treatment of opiate dependence among U.S. substance abuse treatment facilities and their characteristics at the time of the initial availability of the medication. Data come from a 2003 national survey of all substance abuse treatment facilities in the U.S. Out of our sample of 13,060 facilities, 5.5% of facilities reported they offered buprenorphine. Not unexpectedly, the prevalence was higher in certified opioid treatment programs (11.3%) compared to other facilities (4.6%). For opioid treatment programs, offering Naltrexone (OR=8.34, 95% CI=5.53, 12.58) and offering medically supervised withdrawal (OR=2.76, 95% CI=1.38, 5.52) were independent and robust predictors of offering buprenorphine. These same variables were independent predictors for the non-opioid treatment programs as well (Naltrexone, OR=14.32, 95% CI=7.85, 26.10; and medically supervised withdrawal services, OR=4.42, 95% CI=3.01, 6.49). Our results suggest that the adoption of buprenorphine soon after the Food and Drug Administration approved its use for treatment of opioid dependence and the shipping of the medication commenced was associated with facilities already offering pharmacotherapies such as Naltrexone and medically assisted withdrawal. These findings provide baseline data to track the adoption of buprenorphine by substance abuse treatment programs in future years.

  9. 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

  10. 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

  11. Treatment readiness, attitudes toward, and experiences with methadone and buprenorphine maintenance therapy among people who inject drugs in Malaysia

    PubMed Central

    Vijay, Aishwarya; Bazazi, Alexander R.; Yee, Ilias; Kamarulzaman, Adeeba; Altice, Frederick L.

    2016-01-01

    Background Little is known about attitudes toward and experiences with opioid maintenance therapy (OMT) among people who inject drugs in Malaysia, a country where people who inject drugs comprise 1.3% of the adult population. Methods In 2010, 460 people who inject drugs in Greater Kuala Lumpur, Malaysia were surveyed to evaluate attitudes toward and experience with OMT and treatment readiness. Attitudes towards OMT with both methadone and buprenorphine were assessed using an opinions scale. Multivariable linear regression was used to assess correlates of treatment readiness, measured with the 19-item Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). Results All 460 participants used opioids and nearly all (99.1%) met criteria for opioid dependence. Few had had previous experience with methadone (9.3%) or buprenorphine (12.6%) maintenance therapy, yet many had used methadone (55.2%) or buprenorphine (51.7%) outside of treatment settings. Fifteen percent had injected buprenorphine in the past month, and of the few that were currently receiving buprenorphine maintenance therapy, almost all were injecting it. The majority of subjects exhibited a moderate level of treatment readiness and a preference for methadone over buprenorphine. Those with low treatment readiness scores were more likely to have previous experience with compulsory drug detention centers (p<0.01), needle/syringe exchange programs (p<0.005), or be of Indian ethnicity (p<0.001). Past use of methadone (p<0.01), older age (p<0.001), stress symptom severity (p<0.001), and sharing of needles or syringes (p<0.05) were associated with higher treatment readiness scores. Conclusion There are suboptimal levels of OMT experience among people who inject drugs that may be improved by addressing factors that influence patient attitudes. Those individuals with moderate treatment readiness may be targeted by brief motivational and cognitive interventions in primary care, prisons or OMT clinics

  12. 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

  13. 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

  14. 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

  15. 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

  16. Variation in use of Buprenorphine and Methadone Treatment by Racial, Ethnic and Income Characteristics of Residential Social Areas in New York City

    PubMed Central

    Hansen, Helena B.; Siegel, Carole E.; Case, Brady G.; Bertollo, David N.; DiRocco, Danae; Galanter, Marc

    2013-01-01

    National data indicate that patients treated with buprenorphine for opiate use disorders are more likely to be White, highly educated, and to have greater incomes than those receiving methadone, but patterns of buprenorphine dissemination across demographic areas have not been documented in major metropolitan areas where poverty, minority populations and injection heroin use are concentrated. Rates of buprenorphine and methadone treatment are compared among areas of New York City defined by their income and ethnic/racial composition. Residential social areas (hereinafter called social areas) were defined as aggregations of ZIP codes with similar race/ethnicity and income characteristics, and were formed based on clustering techniques. Treatment rates were obtained for each New York City ZIP code: buprenorphine treatment rates were based on the annual number of buprenorphine prescriptions written, and the methadone treatment rate on the number of methadone clinic visits for persons in each ZIP code. Treatment rates were correlated univariately with ethnicity and income characteristics of ZIP codes. Social area treatment rates were compared using individual ANOVA models for each rate. Buprenorphine and methadone treatment rates were significantly correlated with the ethnicity and income characteristics of ZIP codes, and treatment rates differed significantly across the social areas. Buprenorphine treatment rates were highest in the social area with the highest income and lowest percentage of Black and Hispanic residents. Conversely, the methadone treatment rate was highest in the social area with the highest percentage of low income and Hispanic residents. The uneven dissemination of 0pioid maintenance treatment in New York City may be reflective of the limited public health impact of buprenorphine in ethnic minority and low income areas. Specific policy and educational interventions to providers are needed to promote the use of buprenorphine for opiate use disorders

  17. 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

  18. 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…

  19. 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 ...

  20. 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

  1. 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

  2. Clinical experience with fortnightly buprenorphine/naloxone versus buprenorphine in Italy: preliminary observational data in an office-based setting.

    PubMed

    Amato, Patrizia

    2010-01-01

    Buprenorphine/naloxone is a new option for the management of opioid dependence. It has a reduced potential for abuse or misuse compared with methadone and buprenorphine alone, and has a long half-life allowing less frequent dosing. Buprenorphine/naloxone appears to be well suited for the management of opioid dependence in an office-based setting. The aim of this study was to evaluate the efficacy and safety of a buprenorphine/naloxone combination treatment in an office-based setting. Therefore, we evaluated the effect on misuse/diversion, quality of care, quality of life and service delivery. Seventy-eight patients were switched to buprenorphine/naloxone from either methadone or buprenorphine alone; the median duration of previous buprenorphine or methadone treatment was 10 years. Patients received buprenorphine/naloxone and were evaluated throughout a 1-year follow-up period. Treatment was self-administered by the patients every 2 weeks and the mean buprenorphine dosage at 1 year was 8 mg/day. Comparisons were made before and after the switch for patients who switched from buprenorphine alone to buprenorphine/naloxone. Switching to buprenorphine/naloxone was not associated with clinically relevant problems in 50% of patients studied. Buprenorphine/naloxone provided satisfactory coverage of withdrawal symptoms in 78.1% of patients, and 50% of patients were satisfied with buprenorphine/naloxone therapy. Seventy-eight per cent of patients reported improved psychosocial functioning. The majority of patients (approximately 85%) were negative for opioids during toxicological testing. A significantly higher proportion of treatment recipients were highly satisfied during buprenorphine/naloxone administration (p < 0.001 compared with buprenorphine given before the switch). Other outcomes were similar during buprenorphine and buprenorphine/naloxone administration. Fortnightly self-administration of buprenorphine/naloxone appeared to be cost saving for the clinic

  3. From methadone to buprenorphine: changes during a 10 year period within a national opioid maintenance treatment programme.

    PubMed

    Riksheim, Marianne; Gossop, Michael; Clausen, Thomas

    2014-03-01

    Opioid maintenance treatment (OMT) is the most widely used treatment for opioid dependence. Maintenance programmes differ in various aspects and may also change over time. This paper investigates the changes in treatment practices within a national OMT programme during a 10 year period (2002-2011), especially with regard to the prescribing of methadone and buprenorphine. Data (n=34,001) were collected by annual assessments questionnaires. In 2002, only 16% of the OMT patients received buprenorphine as their maintenance medication. By 2011 this percentage had increased significantly (p<.001) to 50.3%. In the same period the number of patients more than tripled (from 1,984 to 6,640, p<.001), and programme attrition rates decreased (p=.020). This relatively rapid shift is a part of the increasing reliance of addiction medicine upon a range of medications administered by different routes which has not been previously charted within a national treatment programme.

  4. 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

  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. 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

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

    PubMed

    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.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. Cost-effectiveness of Extended Buprenorphine-Naloxone Treatment for Opioid-Dependent Youth: Data from a Randomized Trial

    PubMed Central

    Polsky, Daniel; Glick, Henry A.; Yang, Jianing; Subramaniam, Geetha A.; Poole, Sabrina A.; Woody, George E.

    2010-01-01

    Introduction The objective is to estimate cost, net social cost, and cost-effectiveness in a clinical trial of extended buprenorphine-naloxone treatment versus brief detoxification treatment in opioid-dependent youth. Methods Economic evaluation of a clinical trial conducted at 6 community outpatient treatment programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine-naloxone (BUP) or a 14-day taper (DETOX). BUP patients were prescribed up to 24 mg per day for 9 weeks and then tapered to zero at the end of week 12. DETOX patients were prescribed up to 14 mg per day and then tapered to zero on day 14. All were offered twice weekly drug counseling. Data were collected prospectively during the 12-week treatment and at follow-up interviews at months 6, 9, and 12. Results The 12-week outpatient study treatment cost was $1514 (p<0.001) higher for BUP relative to DETOX. One-year total direct medical cost was only $83 higher for BUP (p=0.97). The cost-effectiveness ratio of BUP relative to DETOX was $1,376 in terms of 1-year direct medical cost per quality-adjusted life year (QALY) and $25,049 in terms of outpatient treatment program cost per QALY. The acceptability curve suggests that the cost-effectiveness ratio of BUP relative to DETOX has an 86% chance of being accepted as cost-effective for a threshold of $100,000 per QALY. Conclusions Extended buprenorphine-naloxone treatment relative to brief detoxification is cost effective in the U.S. health care system for the outpatient treatment of opioid-dependent youth. PMID:20626379

  14. Cost Effectiveness of Injectable Extended Release Naltrexone Compared to Methadone Maintenance and Buprenorphine Maintenance Treatment for Opioid Dependence

    PubMed Central

    Jackson, Heide; Mandell, Kara; Johnson, Kimberly; Chatterjee, Debanjana; Vanness, David J.

    2015-01-01

    Background The aim of this study was to estimate the cost-effectiveness of injectable extended release naltrexone (XR-NTX) compared to methadone maintenance and buprenorphine maintenance treatment (MMT and BMT respectively) for adult males enrolled in treatment for opioid dependence in the United States from the perspective of state-level addiction treatment payers. Methods We used a Markov model with daily time cycles to estimate the incremental cost per opioid-free day in a simulated cohort of adult males ages 18–65 over a six-month period from the state health program perspective. Results XR-NTX is predicted to be more effective and more costly than methadone or buprenorphine in our target population, with an incremental cost per opioid-free day gained relative to the next-most effective treatment (MMT) of $72. The cost-effectiveness of XR-NTX relative to MMT was driven by its effectiveness in deterring opioid use while receiving treatment. Conclusions XR-NTX is a cost-effective medication for treating opioid dependence if state addiction treatment payers are willing to pay at least $72 per opioid-free day. PMID:25775099

  15. Interaction Between Buprenorphine and Atazanavir or Atazanavir/Ritonavir

    PubMed Central

    McCance-Katz, Elinore F.; Moody, David E.; Morse, Gene D.; Ma, Qing; DiFrancesco, Robin; Friedland, Gerald; Pade, Patricia; Rainey, Petrie M.

    2007-01-01

    Opioid addiction and HIV disease frequently co-occur. Adverse drug interactions have been reported between methadone and some HIV medications, but less is known about interactions between buprenorphine, an opioid partial agonist used to treat opioid dependence, and HIV therapeutics. This study examined drug interactions between buprenorphine and the protease inhibitors atazanavir and atazanavir/ritonavir. Opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n=10 per protease inhibitor) participated in two 24-hour sessions to determine pharmacokinetics of (1) buprenorphine and (2) buprenorphine and atazanavir (400 mg daily) or atazanavir/ritonavir (300/100 mg daily) following administration for 5 days. Objective opiate withdrawal scale scores and Mini-Mental State Examination were determined prior to and following antiretroviral administration to examine pharmacodynamic effects. Pharmacokinetics of atazanavir and atazanavir/ritonavir were compared in subjects and matched, healthy controls (n=10 per protease inhibitor) to determine effects of buprenorphine. With atazanavir and atazanavir/ritonavir, respectively concentrations of buprenorphine (p<0.001, p<0.001), norbuprenorphine (p=0.026, p=0.006), buprenorphine glucuronide (p=0.002, p<0.001), and norbuprenorphine glucuronide (NS, p=0.037) increased. Buprenorphine treatment did not significantly alter atazanavir or ritonavir concentrations. Three buprenorphine/naloxone-maintained participants reported increased sedation with atazanavir/ritonavir. Atazanavir or atazanavir/ritonavir may increase buprenorphine and buprenorphine metabolite concentrations and might require a decreased buprenorphine dose. PMID:17643869

  16. 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.

  17. 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

  18. “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

  19. 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

  20. 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

  1. 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

  2. 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

  3. Barriers to Primary Care Physicians Prescribing Buprenorphine

    PubMed Central

    Hutchinson, Eliza; Catlin, Mary; Andrilla, C. Holly A.; Baldwin, Laura-Mae; Rosenblatt, Roger A.

    2014-01-01

    PURPOSE Despite the efficacy of buprenorphine-naloxone for the treatment of opioid use disorders, few physicians in Washington State use this clinical tool. To address the acute need for this service, a Rural Opioid Addiction Management Project trained 120 Washington physicians in 2010–2011 to use buprenorphine. We conducted this study to determine what proportion of those trained physicians began prescribing this treatment and identify barriers to incorporating this approach into outpatient practice. METHODS We interviewed 92 of 120 physicians (77%), obtaining demographic information, current prescribing status, clinic characteristics, and barriers to prescribing buprenorphine. Residents and 7 physicians who were prescribing buprenorphine at the time of the course were excluded from the study. We analyzed the responses of the 78 remaining respondents. RESULTS Almost all respondents reported positive attitudes toward buprenorphine, but only 22 (28%) reported prescribing buprenorphine. Most (95%, n = 21) new prescribers were family physicians. Physicians who prescribed buprenorphine were more likely to have partners who had received a waiver to prescribe buprenorphine. A lack of institutional support was associated with not prescribing the medication (P = .04). A lack of mental health and psychosocial support was the most frequently cited barrier by both those who prescribe and who do not prescribe buprenorphine. CONCLUSION Interventions before and after training are needed to increase the number of physicians who offer buprenorphine for treatment of addiction. Targeting physicians in clinics that agree in advance to institute services, coupled with technical assistance after they have completed their training, their clinical teams, and their administrations is likely to help more physicians become active providers of this highly effective outpatient treatment. PMID:24615308

  4. Consumption of buprenorphine and other drugs among heroin addicts under ambulatory treatment: results from cross-sectional studies in 1988 and 1990.

    PubMed

    San, L; Torrens, M; Castillo, C; Porta, M; de la Torre, R

    1993-10-01

    We assessed the prevalence of consumption of buprenorphine and other drugs among heroin addicts under ambulatory treatment in two cross-sectional studies conducted in 1988 (188 subjects) and in 1990 (197 subjects). Patients were enrolled in one of three different programmes: methadone maintenance programme (MMP), antagonist maintenance programme (AMP) and drug-free programme (DFP). Information given by participants was compared with results of urine screening for drugs. Urine samples were tested using enzyme immunoassay for the detection of heroin, cocaine, dextropropoxyphene, cannabis and benzodiazepines, and radioimmunoassay for buprenorphine. Sixty-six percent of patients in 1988 and 71% of patients in 1990 reported having consumed buprenorphine at some time during their history of drug dependence (period prevalence) and 5.9% and 6.1%, respectively, tested positive to the drug (point prevalence). In over 70% of these patients consumption was by the intravenous route. Consumption of cannabis, cocaine and benzodiazepines was also very high in the study population. Overall, patients in the DFP group consumed the largest number of the drugs tested, while those in the AMP group consumed the smallest number. Abuse of buprenorphine could be more widespread than previously reported.

  5. Buprenorphine maintenance treatment retention improves nationally recommended preventive primary care screenings when integrated into urban federally qualified health centers.

    PubMed

    Haddad, Marwan S; Zelenev, Alexei; Altice, Frederick L

    2015-02-01

    Buprenorphine maintenance therapy (BMT) expands treatment access for opioid dependence and can be integrated into primary health-care settings. Treating opioid dependence, however, should ideally improve other aspects of overall health, including preventive services. Therefore, we examined how BMT affects preventive health-care outcomes, specifically nine nationally recommended primary care quality health-care indicators (QHIs), within federally qualified health centers (FQHCs) from an observational cohort study of 266 opioid-dependent patients initiating BMT between 07/01/07 and 11/30/08 within Connecticut's largest FQHC network. Nine nationally recommended preventive QHIs were collected longitudinally from electronic health records, including screening for chronic infections, metabolic conditions, and cancer. A composite QHI score (QHI-S), based on the percentage of eligible QHIs achieved, was categorized as QHI-S ≥80% (recommended) and ≥90% (optimal). The proportion of subjects achieving a composite QHI-S ≥80 and ≥90 % was 57.1 and 28.6%, respectively. Screening was highest for hypertension (91.0%), hepatitis C (80.1%), hepatitis B (76.3%), human immunodeficiency virus (71.4%), and hyperlipidemia (72.9%) and lower for syphilis (49.3%) and cervical (58.5%), breast (44.4%), and colorectal (48.7%) cancer. Achieving QHI-S ≥80% was positively and independently associated with ≥3-month BMT retention (adjusted odds ratio (AOR) = 2.19; 95% confidence interval (CI) = 1.18-4.04) and BMT prescription by primary care providers (PCPs) rather than addiction psychiatric specialists (AOR = 3.38; 95% CI = 1.78-6.37), and negatively with being female (AOR = 0.30; 95% CI = 0.16-0.55). Within primary health-care settings, achieving greater nationally recommended health-care screenings or QHIs was associated with being able to successfully retain patients on buprenorphine longer (3 months or more) and when buprenorphine was prescribed

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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…

  11. 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

  12. 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

  13. 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

  14. 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

  15. [Contingency management in opioid substitution treatment].

    PubMed

    Specka, M; Böning, A; Scherbaum, N

    2011-07-01

    The majority of opiate-dependent patients in substitution treatment show additional substance-related disorders. Concomitant use of heroin, alcohol, benzodiazepines or cocaine compromises treatment success. Concomitant drug use may be treated by using contingency management (CM) which is based on learning theory. In CM, abstinence from drugs, as verified by drug screenings, is reinforced directly and contingently. Reinforcers used in CM studies with substituted patients were, amongst others, vouchers and take-home privileges. Studies in the USA show a medium average effect of CM on drug consumption rates and abstinence. The effects decrease markedly after the end of the intervention. We discuss whether CM is applicable within the German substitution treatment system and how it can be combined with other interventions such as selective detoxification treatments or cognitive-behavioural programmes.

  16. A national study of a telephone support service for patients receiving office-based buprenorphine medication-assisted treatment: study feasibility and sample description.

    PubMed

    Ruetsch, Charles; Cacciola, John; Tkacz, Joseph

    2010-12-01

    Opioid-dependent (OD) patients seeking treatment have multiple treatment options including abstinence-based and medication replacement therapies. A recent and growing addition to medication replacement therapy is buprenorphine medication-assisted treatment (B-MAT), which may be provided by certified physicians practicing in private offices. Research on OD treatment is often performed on samples of patients recruited from specialty treatment facilities, which may not generalize to B-MAT patients. Thus, B-MAT as a treatment approach has been understudied. The present research describes (a) new methods developed to facilitate sample recruitment and survey data collection from a national B-MAT patient sample and (b) a telephonic support program designed for new B-MAT patients. Results indicate that by using appropriate tools, it is feasible to conduct a clinical study of B-MAT patients, recruited at the point of service, and that telephonic patient support was an acceptable treatment adjunct.

  17. Analgesic efficacy of orally administered buprenorphine in rats.

    PubMed

    Martin, L B; Thompson, A C; Martin, T; Kristal, M B

    2001-02-01

    The analgesic effect of orally administered buprenorphine was compared with that induced by a standard therapeutic injected dose (0.05 mg/kg of body weight, s.c.) in male Long-Evans rats. Analgesia was assessed by measuring pain threshold, using the hot-water tail-flick assay before and after administration of buprenorphine. The results suggest that a commonly used formula for oral buprenorphine in flavored gelatin, at a dose of 0.5 mg/kg, does not increase pain threshold in rats. Instead, oral buprenorphine doses of 5 and 10 mg/kg were necessary to induce significant increases in pain threshold. However, these doses had to be administered by orogastric infusion because the rats would not voluntarily eat flavored gelatin containing this much buprenorphine. The depth of analgesia induced by these infused doses was comparable to that induced by the clinically effective s.c. treatment (0.05 mg/kg).

  18. Pain and Associated Substance Use among Opioid Dependent Individuals Seeking Office-Based Treatment with Buprenorphine-Naloxone: A Needs Assessment Study

    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

    Background and Objectives A paucity of studies has examined the pain experiences of opioid dependent individuals seeking office-based buprenorphine-naloxone treatment (BNT). We set out to examine, among those seeking BNT: (a) the prevalence of pain types (i.e., recent pain, chronic pain), (b) the characteristics of pain (intensity, frequency, duration, interference, location, and genesis), and (c) substance use to alleviate pain. Methods We surveyed 244 consecutive individuals seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence about physical pain and associated substance use. Results Thirty-six percent of respondents reported chronic pain (CP) (i.e., pain lasting at least 3 months) and 36% reported “some pain” (SP) (i.e., past week pain not meeting the threshold for CP). In comparison to SP respondents, those with CP were, on average, older; reported greater current pain intensity, pain frequency, typical pain duration, typical pain intensity, and typical pain interference; were more likely to report shoulder or pelvis and less likely to report stomach or arms as their most bothersome pain location; and were more likely to report accident or nerve damage and less likely to report opioid withdrawal as the genesis of their pain. Both pain subgroups reported similarly high rates of past-week substance use to alleviate pain. Conclusions and Scientific Significance The high rates of pain and self-reported substance use to manage pain suggest the importance of assessing and addressing pain in BNT patients. PMID:23617861

  19. 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

  20. 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

  1. BUPRENORPHINE DECREASES THE CCL2-MEDIATED CHEMOTACTIC RESPONSE OF MONOCYTES

    PubMed Central

    Carvallo, Loreto; Lopez, Lillie; Che, Fa-Yun; Lim, Jihyeon; Eugenin, Eliseo; Williams, Dionna W.; Nieves, Edward; Calderon, Tina M.; Madrid-Aliste, Carlos; Fiser, Andras; Weiss, Louis; Angeletti, Ruth Hogue; Berman, Joan W.

    2015-01-01

    Despite successful cART, approximately 60% of HIV infected people exhibit HIV associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9, were identified and had not been shown previously be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction. PMID:25716997

  2. Intravenous misuse of buprenorphine: characteristics and extent among patients undergoing drug maintenance therapy.

    PubMed

    Moratti, Enrico; Kashanpour, Hamid; Lombardelli, Tiziana; Maisto, Maria

    2010-01-01

    Sublingual buprenorphine [Subutex(R)] is used to treat opioid dependence. However, illicit intravenous (IV) injection of buprenorphine is a widespread problem. This survey investigated the IV misuse of buprenorphine among patients receiving drug replacement therapy at the Drug Addiction Centre in Udine, Italy. All patients who were receiving treatment with buprenorphine or methadone at the Drug Addiction Centre were invited to fill in a voluntary and anonymous questionnaire consisting of five questions. The questions asked if the patient had ever misused buprenorphine intravenously, when the misuse had occurred, the patient's reasons for misusing buprenorphine, the patient's perception of their experience, and the patient's perception of how widespread IV misuse of buprenorphine is. 307 patients completed the questionnaire, 93 and 214 of whom, respectively, were receiving buprenorphine and methadone. In total, 23.12% of patients admitted an IV misuse of buprenorphine, with a significantly greater prevalence among patients currently receiving buprenorphine (35.48%) than those receiving methadone (17.75%; p < 0.001). Younger patients were also more likely to have misused buprenorphine, and tended to have done so before coming to the Drug Addiction Centre. The most frequent motivation for IV misuse was treatment of heroin addiction or withdrawal symptoms (50.71%), while only 12.67% of patients reported that their motivation was to experience pleasure or euphoria. The majority of patients who had misused buprenorphine intravenously (53.52%) had a negative experience, and methadone recipients were significantly more likely to find the experience negative than buprenorphine recipients (68.42% vs 36.36%; p = 0.007). Almost half of the patients (45.93%) thought that at least 50% of patients had taken buprenorphine by IV injection. The results of our study confirm the widespread IV misuse of buprenorphine. Misuse was most common among patients currently receiving

  3. 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

  4. 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

  5. Dose-Dependent Flux of Buprenorphine Following Transdermal Administration in Healthy Subjects.

    PubMed

    Wang, Yi; Cipriano, Alessandra; Munera, Catherine; Harris, Stephen C

    2016-10-01

    Buprenorphine transdermal delivery system (BTDS) applied once every 7 days is indicated for the management of pain that is severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. The 7-day flux of buprenorphine from BTDS to systemic circulation was investigated in a phase 1, 2-period crossover study with 3 randomized groups of healthy subjects receiving BTDS containing buprenorphine 5, 10, or 20 mg for 7 days preceded or followed by intravenous buprenorphine infusion (25 μg/h for 24 hours). Residual and absolute bioavailability methods were used to estimate 7-day flux of buprenorphine. Following BTDS administration, mean area under the curve of buprenorphine increased proportionally (12.6, 24.3, and 51.1 ng/[mL · h]), maximum mean plasma concentration rose with increasing dose (176, 191, and 471 pg/mL), and absolute bioavailability was 14% to 16%. Mean residual amount of buprenorphine in the BTDS after 7-day application was 4.50, 8.57, and 17.1 mg. Flux of buprenorphine was approximately 5, 10, and 20 μg/h for BTDS containing 5, 10, and 20 mg buprenorphine, respectively. BTDS was safe and well tolerated following a single 7-day application in healthy subjects. The results of this study demonstrated dose-dependent flux of buprenorphine delivered via transdermal system. PMID:26865472

  6. 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

  7. The antinociceptive efficacy of buprenorphine administered through the drinking water of rats.

    PubMed

    Jessen, L; Christensen, S; Bjerrum, O J

    2007-04-01

    Postoperative pain management in laboratory animals is important for animal welfare and required under law in many countries. Frequent injection of analgesics to rodents after surgery is stressful for the animals and labour-intensive for animal care personnel. An alternative dosing scheme such as administration of analgesics in the drinking water would be desirable. However, the efficacy of a chronic oral analgesic treatment via this route has not yet been documented. This study investigated the antinociceptive efficacy of buprenorphine administered ad libitum via the drinking water of laboratory rats. The antinociceptive efficacy of buprenorphine in drinking water was compared with repeated subcutaneous injections. A comparison was also made between buprenorphine in drinking water and the combination of one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water. Antinociception was assessed by use of an analgesiometric model measuring the rats' latency time to withdrawal from a noxious heat stimulus applied to the plantar surface of the paw. Results revealed that buprenorphine in drinking water (0.056 mg/mL) induced significant increases in paw withdrawal latency times during a three-day period of administration with a maximal effect at 39 h after the start of buprenorphine administration. One single injection of buprenorphine (0.1 mg/kg s.c.) followed by buprenorphine in the drinking water (0.056 mg/mL) induced an earlier onset of antinociception than buprenorphine in drinking water alone. In contrast, buprenorphine (0.1 mg/kg s.c.) injected every 8 h over a period of three days did not result in significant increases in paw withdrawal latency times. In conclusion, our results suggest that one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water may be a viable treatment option for the relief of pain in laboratory rats, but at the doses used in this study in pain-free rats it was associated

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Assessment and management of opioid withdrawal symptoms in buprenorphine-dependent subjects.

    PubMed

    San, L; Camí, J; Fernández, T; Ollé, J M; Peri, J M; Torrens, M

    1992-01-01

    The spontaneous physical dependence of buprenorphine was assessed in opioid addicts who switched from heroin to sublingual or intravenous buprenorphine. Twenty-two patients were randomly assigned to double-blind administration of methadone (n = 11) or placebo (n = 11) for 13 days after abrupt withdrawal of buprenorphine. Methadone was administered according to four pre-established dosing schedules depending on the previous amount of daily consumed buprenorphine. No methadone-treated patient required modification of the therapeutic regimen, whereas eight of eleven placebo-treated patients needed treatment with methadone. Buprenorphine withdrawal syndrome was of opioid type, began somewhat more slowly, and showed a peak until day 5. The occurrence, time-course and characteristics of buprenorphine withdrawal syndrome make it necessary to reconsider the abuse potential of this analgesic.

  13. 78 FR 34108 - Determination That SUBOXONE (Buprenorphine Hydrochloride and Naloxone Hydrochloride) Sublingual...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-06

    .... SUBOXONE is indicated for maintenance treatment of opioid dependence. In a letter dated September 18, 2012... require all manufacturers of buprenorphine-containing products for the treatment of opioid dependence to... for buprenorphine HCl and naloxone HCl products for opioid dependence until the Agency...

  14. 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

  15. 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

  16. Safety and efficacy of buprenorphine/naloxone in opioid-dependent patients: an Italian observational study.

    PubMed

    Magnelli, Fernanda; Biondi, Lorita; Calabria, Roberto; Fiore, Angelo; Peluso, Eugenio; Vonella, Domenico; Rota, Amerigo Giuseppe

    2010-01-01

    Opioid dependence is a growing problem. Methadone is an established agent for the treatment of opioid dependence, but there is a risk of this agent being abused, a potential for interaction with antiretroviral agents and a risk of cardiac toxicity. Another option is the partial mu-opioid receptor opioid agonist buprenorphine, which has been used successfully to manage opioid dependence. While the risk of abuse is lower than that for methadone, there is still a risk. The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is a newer agent with reduced abuse potential, and has been shown to have promising efficacy for opioid dependence. We describe the results of an observational study investigating the safety and efficacy of buprenorphine/naloxone in opioid-dependent patients. A total of 77 patients were included and were switched from buprenorphine to sublingual tables of buprenorphine/naloxone; the buprenorphine dosage was titrated to achieve good control of withdrawal symptoms. The prevalence of withdrawal symptoms, craving, constipation, cramps, insomnia, sexual activity, depression, sweating, distress, bone/joint pain and drowsiness were compared over the first 30 days of treatment (period 1) and the total 120-day study duration (period 2). The average buprenorphine/naloxone dose in period 1 was 7.3 mg/day and 12.7 mg/day in period 2. Most patients did not experience any withdrawal symptoms in either period 1 or period 2. Fewer than 20% of patients experienced any cravings over the 120-day study period. Importantly, the adverse effects observed were usually mild, with very few patients experiencing significant adverse effects. This study shows that buprenorphine/naloxone is an effective and well tolerated treatment for opioid withdrawal when the dosage is titrated to achieve good control of withdrawal symptoms. Switching from buprenorphine alone to buprenorphine/naloxone was possible with very

  17. Facilitators and barriers in implementing buprenorphine in the Veterans Health Administration.

    PubMed

    Gordon, Adam J; Kavanagh, Greg; Krumm, Margaret; Ramgopal, Rajeev; Paidisetty, Sanjay; Aghevli, Minu; Goodman, Francine; Trafton, Jodie; Liberto, Joseph

    2011-06-01

    Opioid dependence is a chronic, relapsing disorder that deleteriously influences the health of those afflicted. Sublingual buprenorphine opioid agonist treatment (OAT) has been shown to be safe, effective, and cost-effective for the treatment of opioid dependence in nonspecialized, office-based settings, including the Veterans Health Administration (VHA). We sought to examine and describe provider-, facility-, and system-level barriers and facilitators to implementing buprenorphine therapy within the VHA. From June 2006 to October 2007, we conducted semistructured telephone interviews of key personnel at a national sample of VHA facilities with high prevalence of opioid dependence and without methadone OAT programs. Sites were categorized based on the number of veterans receiving buprenorphine prescriptions: More Buprenorphine (MB, >40 prescriptions, 5 sites), Some Buprenorphine (SB, 5-40 prescriptions, 3 sites), and No Buprenorphine (NB, 0-5 prescriptions, 9 sites). Interviews were taped, transcribed, and coded; consensus of coding themes was reached; and data were evaluated using grounded theory. Sixty-two staff members were interviewed. For NB sites, perceived patient barriers included lack of need and attitudes/stigma associated with opioid dependence. Provider barriers included lack of interest, stigma toward the population, and lack of education about buprenorphine-OAT. Prominent facilitators at MB sites included having established need, provider interest, and resources/time available for buprenorphine-OAT. The presence of a champion/role-model for buprenorphine care greatly facilitated its implementation. We conclude that factors that enable or impede buprenorphine-OAT vary by facility. Strategies and policies to encourage implementation of buprenorphine should be adaptable and target needs of each facility.

  18. 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.

  19. 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

  20. 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

  1. 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…

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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…

  9. Management of opioid painkiller dependence in primary care: ongoing recovery with buprenorphine/naloxone.

    PubMed

    Hard, Bernadette

    2014-11-28

    Opioid painkiller dependence is a growing problem and best-practice management is not well defined. We report a case of a young woman exhibiting dependence on codeine, originally prescribed for myalgic encephalopathy, after escalating use over a 10-year period. In 2012, a consultation with a new general practitioner, who had extensive experience of patients with substance abuse, revealed the underlying dependence. After building trust for 6 months, she was able to admit to medication abuse, and was referred to the community drug and alcohol team. On presentation to the team, the patient had no pain issues and the dihydrocodeine use--600 tablets/week--solely reflected her dependence. The patient successfully underwent rapid induction with buprenorphine/naloxone as opioid substitution treatment over 2 days. She is currently stable, engaged with recovery support services and psychosocial counselling, and has just returned to work. She is maintained on a therapeutic dose of buprenorphine 10 mg/naloxone 2.5 mg.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. Discontinuation of buprenorphine maintenance therapy: perspectives and outcomes.

    PubMed

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

    2015-05-01

    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.

  15. Sublingual buprenorphine for chronic pain: A survey of clinician prescribing practices

    PubMed Central

    Rosen, Kristen; Gutierrez, Antonio; Haller, Deborah; Potter, Jennifer Sharpe

    2013-01-01

    Objectives Sublingual buprenorphine, with and without naloxone, is indicated for the treatment of opioid use disorders. Although not approved for pain, some evidence suggests it may be a safe and effective alternative to conventional opioid analgesics, particularly for those with addiction problems. This study surveyed pain specialists to examine the extent to which sublingual buprenorphine was prescribed for chronic pain and explore associated clinician attitudes and characteristics. Method A 36-item survey examining clinician attitudes and characteristics related to sublingual buprenorphine and other opioids was distributed to 1,307 members of the American Pain Society, a multi-disciplinary professional group. Members were provided a paper copy of the survey and URL to an on-line version. A follow up letter was mailed after 2 weeks. Results Overall, 230 completed surveys were returned (18.5%). Of clinicians who prescribed opioids for chronic pain (92.5%), 19.7% reported prescribing sublingual buprenorphine for chronic pain at least once; of these prescribers, 39.6% did not have a DEA X-waiver to prescribe sublingual buprenorphine for opioid dependance. Prescribers were more likely than non-prescribers to find sublingual buprenorphine effective for chronic pain. Prescribers were also significantly more likely to view sublingual buprenorphine as safer than full agonists in terms of addiction, overdose, and drug interaction. No differences emerged between prescribers and non-prescribers regarding perceptions of potential for drug diversion or in terms of overall opioid prescribing behaviors. Discussion Results suggest that sublingual buprenorphine is indeed being used to treat chronic pain; however, the circumstances when this occurs are not entirely clear. PMID:23727654

  16. 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

  17. Buprenorphine and methadone for opioid addiction during pregnancy.

    PubMed

    Mozurkewich, Ellen L; Rayburn, William F

    2014-06-01

    Buprenorphine and methadone are opioid-receptor agonists used as opioid substitution therapy during pregnancy to limit exposure of the fetus to cycles of opioid withdrawal and reduce the risk of infectious comorbidities of illicit opioid use. As part of a comprehensive care plan, such therapy may result in improved access to prenatal care, reduced illicit drug use, reduced exposure to infections associated with intravenous drug use, and improved maternal nutrition and infant birth weight. This article describes differences in patient selection between the two drugs, their relative safety during pregnancy, and changes in daily doses as a guide for prescribing clinicians.

  18. 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

  19. 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

  20. Buprenorphine in drug-facilitated sexual abuse: a fatal case involving a 14-year-old boy.

    PubMed

    Kintz, Pascal; Villain, Marion; Tracqui, Antoine; Cirimele, Vincent; Ludes, Bertrand

    2003-10-01

    The first case involving repetitive sexual abuse linked to the use of buprenorphine is reported. Under the tradename Subutex, buprenorphine is largely used for the substitution management of opiate-dependent individuals, but it can also be easily found on the black market. A 14-year-old boy was found dead at the home of a well-known sex offender of minors. At the autopsy, no particular morphological changes were noted, except for pulmonary and visceral congestion. There was no evidence of violence, and no needle marks were found by the pathologist. Toxicological analyses, as achieved by liquid chromatography-mass spectrometry, demonstrated both recent and repetitive buprenorphine exposure in combination with nordiazepam. Buprenorphine concentrations were 1.1 ng/mL and 23 pg/mg in blood and hair, respectively. The boy's death was attributed to accidental asphyxia in a facilitated repetitive sexual abuse situation due to the combination of buprenorphine and benzodiazepines, even at therapeutic concentrations. The use of buprenorphine as a sedative drug was not challenged by the perpetrator. PMID:14607012

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. [Breast feeding during methadon- and buprenorphin therapy].

    PubMed

    Müller, M J; Lange, M; Paul, T; Seeliger, S

    2011-12-01

    The number of opiate addicted patients treated with opioid replacement therapy is continuously increasing. In Germany, 57.7% of these patients are treated with methadone and 18.6% with buprenorphine. This maintenance therapy provides several advantages while addicted pregnant women and their foetus have a high benefit from appropriate replacement therapy. However, the recommendations concerning breast feeding during an opioid replacement therapy are discussed controversially, because methadone as well as buprenorphine accumulate in breast milk. This accumulation might cause damages to the newborn's health; so, child benefits of breast feeding have to be balanced with possible health risks.This review provides an overview of a selective literature search based on the PubMed-database and german consensus recommendations. Used search terms included: (methadone*) AND (breastfeeding OR lactation), (methadone*) AND (human milk), (buprenorphine*) AND (breastfeeding OR lactation) and (buprenorphine*) AND (human milk).According to the available literature, addicted women, substinated with methadone or buprenorphine are allowed to breast feed their newborns. The advantages of breast feeding prevail the risks of an infant opiate intoxication caused by methadone or buprenorphine.

  11. 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

  12. 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

  13. 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

  14. Effects of regulation on methadone and buprenorphine provision in the wake of Hurricane Sandy.

    PubMed

    McClure, Bridget; Mendoza, Sonia; Duncan, Laura; Rotrosen, John; Hansen, Helena

    2014-10-01

    Hurricane Sandy led to the closing of many major New York City public hospitals including their substance abuse clinics and methadone programs, and the displacement or relocation of thousands of opioid-dependent patients from treatment. The disaster provided a natural experiment that revealed the relative strengths and weaknesses of methadone treatment in comparison to physician office-based buprenorphine treatment for opioid dependence, two modalities of opioid maintenance with markedly different regulatory requirements and institutional procedures. To assess these two modalities of treatment under emergency conditions, semi-structured interviews about barriers to and facilitators of continuity of care for methadone and buprenorphine patients were conducted with 50 providers of opioid maintenance treatment. Major findings included that methadone programs presented more regulatory barriers for providers, difficulty with dose verification due to impaired communication, and an over reliance on emergency room dosing leading to unsafe or suboptimal dosing. Buprenorphine treatment presented fewer regulatory barriers, but buprenorphine providers had little to no cross-coverage options compared to methadone providers, who could refer to alternate methadone programs. The findings point to the need for well-defined emergency procedures with flexibility around regulations, the need for a central registry with patient dose information, as well as stronger professional networks and cross-coverage procedures. These interventions would improve day-to-day services for opioid-maintained patients as well as services under emergency conditions.

  15. 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

    2015-09-15

    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.

  16. 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

  17. Randomized, Placebo-Controlled Pilot Trial of Gabapentin During an Outpatient, Buprenorphine-Assisted Detoxification Procedure1

    PubMed Central

    Sanders, Nichole C.; Mancino, Michael J.; Gentry, W. Brooks; Guise, J. Benjamin; Bickel, Warren K.; Thostenson, Jeff; Oliveto, Alison H.

    2014-01-01

    This pilot study examined the efficacy of the N-type calcium channel blocker gabapentin to improve outcomes during a brief detoxification protocol with buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a 5-wk, double blind, placebo-controlled trial examining the effects of gabapentin during a 10-day outpatient detoxification from buprenorphine. Participants were inducted onto buprenorphine sublingual tablets during week 1, were randomized and inducted onto gabapentin or placebo during week 2, underwent a 10-day buprenorphine taper during weeks 3–4 and then were tapered off gabapentin/placebo during week 5. Assessments included thrice-weekly opioid withdrawal scales, vitals, and urine drug screens. Twenty-four individuals (13 male, 17 Caucasian, 3 African American, 4 Latino, mean age 29.7 yrs) participated in the detoxification portion of the study (gabapentin, N=11; placebo, N=13). Baseline characteristics did not differ significantly between groups. Self-reported and observer-rated opioid withdrawal ratings were relatively low and did not differ between groups during the buprenorphine taper. Urine results showed a drug x time interaction, such that the probability of opioid-positive urines significantly decreased over time in the gabapentin versus placebo groups during weeks 3–4 (OR=0.73, p=0.004). These results suggest that gabapentin reduces opioid use during a 10-day buprenorphine detoxification procedure. PMID:23855333

  18. 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

  19. A new highly specific buprenorphine immunoassay for monitoring buprenorphine compliance and abuse.

    PubMed

    Melanson, Stacy E F; Snyder, Marion L; Jarolim, Petr; Flood, James G

    2012-04-01

    Urine buprenorphine screening is utilized to assess buprenorphine compliance and to detect illicit use. Robust screening assays should be specific for buprenorphine without cross-reactivity with other opioids, which are frequently present in patients treated for opioid addiction and chronic pain. We evaluated the new Lin-Zhi urine buprenorphine enzyme immunoassay (EIA) as a potentially more specific alternative to the Microgenics cloned enzyme donor immunoassay (CEDIA) by using 149 urines originating from patients treated for chronic pain and opioid addiction. The EIA methodology offered specific detection of buprenorphine use (100%) (106/106) and provided superior overall agreement with liquid chromatography-tandem mass spectrometry, 95% (142/149) and 91% (135/149) using 5 ng/mL (EIA[5]) and 10 ng/mL (EIA[10]) cutoffs, respectively, compared to CEDIA, 79% (117/149). CEDIA generated 27 false positives, most of which were observed in patients positive for other opioids, providing an overall specificity of 75% (79/106). CEDIA also demonstrated interference from structurally unrelated drugs, chloroquine and hydroxychloroquine. CEDIA and EIA[5] yielded similar sensitivities, both detecting 96% (22/23) of positive samples from patients prescribed buprenorphine, and 88% (38/43) and 81% (35/43), respectively, of all positive samples (illicit and prescribed users). The EIA methodology provides highly specific and sensitive detection of buprenorphine use, without the potential for opioid cross-reactivity.

  20. 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

  1. 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

  2. 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

  3. Methadone and buprenorphine for the management of opioid dependence in pregnancy.

    PubMed

    Jones, Hendrée E; Finnegan, Loretta P; Kaltenbach, Karol

    2012-04-16

    This article provides an overview and discussion of the collective maternal, fetal and neonatal outcome research on women maintained on methadone or buprenorphine during pregnancy. Its focus is on an assessment of the comparative effectiveness of methadone and buprenorphine pharmacotherapy, with particular attention given to recent findings from the literature. Recommendations for clinical practice are outlined, and directions for future research are presented. Findings from comparative studies of methadone and buprenorphine underscore the efficacy of both medications in preventing relapse to illicit opioid use in the treatment of opioid-dependent pregnant patients, as well as the simplicity of induction onto methadone and patient retention while receiving such therapy. Fetal monitoring suggests that buprenorphine results in less fetal cardiac and movement suppression than does methadone. The clinical implications of these findings need future exploration. For the neonate, evidence from studies using a wide range of designs, including retrospective chart reviews, prospective observational studies, and randomized clinical trials, show consistent results, with prenatal exposure to buprenorphine resulting in less severe neonatal abstinence syndrome relative to methadone. Any medication given to pregnant women should be prescribed only after considering the risk : benefit ratio for the maternal-fetal dyad. Medication choices for each opioid-dependent patient during pregnancy need to be made on a patient-by-patient basis, taking into consideration the patient's opioid dependence history, previous and current treatment experiences, medical circumstances and treatment preferences. Moreover, for a full remission of opioid addiction to be sustainable, both post-partum and across the lifespan, treatment providers must not rely solely on medication to treat their patients but should also utilize women-specific comprehensive treatment models that address the underlying

  4. 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

  5. “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

  6. Patient perspectives associated with intended duration of buprenorphine maintenance therapy

    PubMed Central

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

    2015-01-01

    Patients with opioid use disorders frequently discontinue opioid maintenance therapy (OMT) prematurely, reducing retention and possibly limiting the efficacy of OMT. The current study is a cross-sectional survey of patients (N = 69) enrolled in buprenorphine maintenance therapy (BMT). We examined patient demographics, BMT characteristics (e.g., dose, time in BMT), and patient perspectives regarding intended duration of BMT. In addition, patients’ reasons for continuing or discontinuing BMT were investigated. Results revealed that the majority (82%) of participants reported wanting to continue BMT for at least 12 months. Age at first drug use, time in BMT, concern about pain, and concern about relapse were all positively associated with intended duration of BMT. The following were negatively associated with intended duration of BMT: recent discussion with a treatment provider about BMT discontinuation, prior attempt to discontinue BMT, concern about withdrawal symptoms, experiencing pleasurable effects from taking buprenorphine, and perceived conflicts of BMT with life, work, or school obligations. The most common reasons for wanting to continue BMT included concerns about withdrawal symptoms, relapse, and pain. Although preliminary, the findings highlight key issues with regard to patients’ perspectives of BMT. The results of this study provide information that may be useful in improving OMT programs and treatment outcomes. PMID:25899872

  7. Patient Perspectives Associated with Intended Duration of Buprenorphine Maintenance Therapy.

    PubMed

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

    2015-09-01

    Patients with opioid use disorders frequently discontinue opioid maintenance therapy (OMT) prematurely, reducing retention and possibly limiting the efficacy of OMT. The current study is a cross-sectional survey of patients (N=69) enrolled in buprenorphine maintenance therapy (BMT). We examined patient demographics, BMT characteristics (e.g., dose, time in BMT), and patient perspectives regarding intended duration of BMT. In addition, patients' reasons for continuing or discontinuing BMT were investigated. Results revealed that the majority (82%) of participants reported wanting to continue BMT for at least 12months. Age at first drug use, time in BMT, concern about pain, and concern about relapse were all positively associated with intended duration of BMT. The following were negatively associated with intended duration of BMT: recent discussion with a treatment provider about BMT discontinuation, prior attempt to discontinue BMT, concern about withdrawal symptoms, experiencing pleasurable effects from taking buprenorphine, and perceived conflicts of BMT with life, work, or school obligations. The most common reasons for wanting to continue BMT included concerns about withdrawal symptoms, relapse, and pain. Although preliminary, the findings highlight key issues with regard to patients' perspectives of BMT. The results of this study provide information that may be useful in improving OMT programs and treatment outcomes.

  8. Validation of the Immunalysis microplate ELISA for the detection of buprenorphine and its metabolite norbuprenorphine in urine.

    PubMed

    Miller, Eleanor I; Torrance, Hazel J; Oliver, John S

    2006-03-01

    The purpose of this study was to validate the Immunalysis Buprenorphine Microplate enzyme-linked immunosorbent assay (ELISA) for the detection of buprenorphine in urine samples. Sixty-nine urine samples were obtained from volunteers on the Subutex treatment program and from routine samples submitted to the laboratory for buprenorphine testing. For ELISA analysis, samples were diluted 1:10 with K(2)HPO(4) (0.1M, pH 7.0). The limit of detection was calculated as 0.5 ng/mL buprenorphine. The intra-assay and interday precision was 3.8% (n = 10) and 8.6% (n = 50) respectively at 1 ng/mL buprenorphine. At a low concentration of norbuprenorphine (1 ng/mL), the immunoassay demonstrated a cross-reactivity of 78%. A higher cross-reactivity of 116% was observed at a higher concentration of norbuprenorphine (10 ng/mL). Dihydrocodeine, codeine, tramadol, morphine, propoxyphene, methadone, and EDDP were tested at concentrations of 10 ng/mL and 10,000 ng/mL and demonstrated no cross-reactivity with the assay. For liquid chromatography-tandem mass spectrometry (LC-MS-MS), deuterated internal standard mixture, 1M acetate buffer (pH 5.0), and b-glucuronidase were added to the standards and samples, which were then incubated for 3 h at 60 degrees C. After incubation, 3 mL K(2)HPO(4) (0.1M, pH 6.0) was added and the pH altered to pH 6.0 using 1M KOH. Buprenorphine and norbuprenorphine were subsequently extracted by solid-phase. Twenty-one samples were confirmed positive and 48 samples were confirmed negative by LC-MS-MS. Using a cut-off value of 0.5 ng/mL buprenorphine, the immunoassay demonstrated a sensitivity and specificity of 100%. PMID:16620543

  9. Prenatal buprenorphine exposure decreases neurogenesis in rats.

    PubMed

    Wu, Chih-Cheng; Hung, Chih-Jen; Shen, Ching-Hui; Chen, Wen-Ying; Chang, Cheng-Yi; Pan, Hung-Chuan; Liao, Su-Lan; Chen, Chun-Jung

    2014-02-10

    Perinatal opioid exposure has a negative effect on neurogenesis and produces neurological consequences. However, its mechanisms of action are incompletely understood. Buprenorphine, a mixed opioid agonist/antagonist, is an alternative medication for managing pregnant opioid addicts. This study provides evidence of decreased neurogenesis and depression-like consequences following prenatal exposure to buprenorphine and sheds light on mechanisms of action in a rat model involving administration of intraperitoneal injection to pregnant rats starting from gestation day 7 and lasting for 14 days and a cultured neurosphere model. Results of forced swimming test and tail suspension test showed that pups at postnatal day 21 had worse parameters of depression-like neurobehaviors, independent of gender. Neurobehavioral changes were accompanied by reduction of neuronal composition, biochemical parameters of neural stem/progenitor cells, brain-derived neurotrophic factor (BDNF) expression, tropomyosin-related kinase receptor type B phosphorylation, protein kinase A (PKA) activity, and cAMP response element-binding protein phosphorylation. Results of parallel cell studies further demonstrated a negative impact of buprenorphine on cultured neurospheres, including proliferation, differentiation, BDNF expression and signaling, and PKA activity. Taken together, our results suggest that prenatal exposure to buprenorphine might result in depression-like phenotypes associated with impaired BDNF action and decreased neurogenesis in the developing brain of weanlings.

  10. 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

  11. Effects of Dexmedetomidine and Ketamine-Dexmedetomidine with and without Buprenorphine on Corticoadrenal Function in Rabbits.

    PubMed

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

    2015-05-01

    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.

  12. 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

  13. 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

  14. 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

  15. [Research progress of blood substitutes for the treatment of hemorrhagic shock].

    PubMed

    Song, Junlu; Wang, Xiang

    2010-04-01

    Hemorrhagic shock is a medical complication caused by the reduction of circulation blood in body. The routine treatment of hemorrhagic shock is to infuse blood or substitute. However, the duration of blood storage is short,the procedures for matching of blood are necessary, and there is the risk of spreading some hematogenous diseases. All these have limited the use of blood-transfusion in the emergent situations such as disaster and war. Thus, the research of blood substitutes is promoted. Considering the scarcity of domestic research report on the use of blood substitutes for the treatment of hemorrhagic shock, we present an overview in this paper.

  16. 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

  17. 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

  18. 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

  19. A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings

    PubMed Central

    Wurst, Keele E.; Zedler, Barbara K.; Joyce, Andrew R.; Sasinowski, Maciek; Murrelle, E. Lenn

    2016-01-01

    BACKGROUND Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. OBJECTIVE The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. METHODS Pregnant women and their corresponding births during 2005–2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher’s exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. RESULTS A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby’s father. CONCLUSIONS An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment

  20. A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings

    PubMed Central

    Wurst, Keele E.; Zedler, Barbara K.; Joyce, Andrew R.; Sasinowski, Maciek; Murrelle, E. Lenn

    2016-01-01

    BACKGROUND Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. OBJECTIVE The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. METHODS Pregnant women and their corresponding births during 2005–2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher’s exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. RESULTS A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby’s father. CONCLUSIONS An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment

  1. 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

  2. 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

  3. 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

  4. Adherence to HIV treatment among IDUs and the role of opioid substitution treatment (OST).

    PubMed

    Spire, Bruno; Lucas, Gregory M; Carrieri, M Patrizia

    2007-08-01

    In the era of highly effective anti-retroviral therapy (ART), data show a significant difference in treatment outcomes between injecting drug users (IDUs) and non-IDUs. Factors that may contribute to suboptimal treatment outcomes in IDUs include delayed access to ART, competing comorbid diseases, psychosocial barriers and poor long-term adherence to ART. This review describes and compares several studies on adherence to ART and its correlates in HIV-infected individuals in general, then IDUs and finally those IDUs on opioid substitution treatment (OST). It highlights how ongoing drug use or OST can modify the pattern of these correlates. The aim is to extend all the experience acquired from these studies in order to optimise both access to care and adherence in those countries where HIV infection is mainly driven by IDUs and where ART and OST are only starting to be scaled up. The role of OST in fostering access to care and adherence to ART together with the promising results achieved to date using modified directly observed therapy (DOT) programs for patients taking methadone, allow us to emphasize the efficacy of a comprehensive care model which integrates substance dependence treatment, psychiatric treatment, social services, and medical treatment. The review concludes by suggesting areas of future research targeted at improving the understanding of both the role of perceived toxicity and patient-provider relationship for patients on ART and OST.

  5. CASE REPORT OF SUBSTANCE DEPENDENCE WITH BUPRENORPHINE AND MEPHENTERMINE

    PubMed Central

    Mendhekar, D.N.; Sharma, Himanshu; Dali, J.S.

    1999-01-01

    Here is reported an unusual case of substance dependence with buprenorphine, mephentermine, & promethazine. This combination taken through intramuscular route produced a relatively mild & delayed abstinence syndrome with features viz. increased sleep and appetite in the patients. The neurophysiological basis for use of this rare form of additive (mephentermine) with buprenorphine is speculated. PMID:21455380

  6. 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

  7. 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

  8. 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

  9. 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...

  10. 40 CFR 148.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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...

  11. 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...

  12. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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... restricted waste or the residual from treatment of a restricted waste as a substitute for adequate...

  13. 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...

  14. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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... restricted waste or the residual from treatment of a restricted waste as a substitute for adequate...

  15. 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...

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. Indicators of buprenorphine and methadone use and abuse: what do we know?

    PubMed

    Maxwell, Jane Carlisle; McCance-Katz, Elinore F

    2010-01-01

    Abuse of prescription opioids is a growing problem. The number of methadone pain pills distributed now exceeds liquid methadone used in opioid treatment, and the increases in buprenorphine indicators provide evidence of the need to monitor and intervene to decrease the abuse of this drug. The need for additional and improved data to track trends is discussed, along with findings as to the characteristics of the users and combinations of drugs. Data on toxicities related to methadone or buprenorphine, particularly in combination with other prescribed drugs, are presented and clinical implications and considerations are offered. These findings underscore the need for physicians to be aware of potential toxicities and to educate their patients regarding these issues. PMID:20132124

  2. Psychiatric comorbidity, red flag behaviors, and associated outcomes among office-based buprenorphine patients following Hurricane Sandy.

    PubMed

    Williams, Arthur R; Tofighi, Babak; Rotrosen, John; Lee, Joshua D; Grossman, Ellie

    2014-04-01

    In October 2012, Bellevue Hospital Center (Bellevue) in New York City was temporarily closed as a result of Hurricane Sandy, the largest hurricane in US history. Bellevue's primary care office-based buprenorphine program was temporarily closed and later relocated to an affiliate public hospital. Previous research indicates that the relationships between disaster exposure, substance use patterns, psychiatric symptoms, and mental health services utilization is complex, with often conflicting findings regarding post-event outcomes (on the individual and community level) and antecedent risk factors. In general, increased use of tobacco, alcohol, and illicit drugs is associated with both greater disaster exposure and the development or exacerbation of other psychiatric symptoms and need for treatment. To date, there is limited published information regarding post-disaster outcomes among patients enrolled in office-based buprenorphine treatment, as the treatment modality has only been relatively approved recently. Patients enrolled in the buprenorphine program at the time of the storm were surveyed for self-reported buprenorphine adherence and illicit substance and alcohol use, as well as disaster-related personal consequences and psychiatric sequelae post-storm. Baseline demographic characteristics and insurance status were available from the medical record. Analysis was descriptive (counts and proportions) and qualitative, coding open-ended responses for emergent themes. There were 132 patients enrolled in the program at the time of the storm; of those, 91 were contacted and 89 completed the survey. Almost half of respondents reported disruption of their buprenorphine supply. Unexpectedly, patients with psychiatric comorbidity were no more likely to report increased use/relapse as a result. Rather, major risk factors associated with increased use or relapse post-storm were: (1) shorter length of time in treatment, (2) exposure to storm losses such as buprenorphine

  3. Methadone and Buprenorphine Prescribing and Referral Practices in US Prison Systems: Results from a Nationwide Survey

    PubMed Central

    Nunn, Amy; Zaller, Nickolas; Dickman, Samuel; Trimbur, Catherine; Nijhawan, Ank; Rich, Josiah D.

    2009-01-01

    Background More than 50% of incarcerated individuals have a history of substance use, and over 200,000 individuals with heroin addiction pass through American correctional facilities annually. Opiate replacement therapy (ORT) with methadone or buprenorphine is an effective treatment for opiate dependence and can reduce drug-related disease and recidivism for inmates. Provision of ORT is nevertheless a frequently neglected intervention in the correctional setting. Objective and Methods We surveyed the 50 state; Washington, District of Columbia (DC); and Federal Department of Corrections' medical directors or their equivalents about their facilities' ORT prescribing policies and referral programs for inmates leaving prison. Results We received responses from 51 of 52 prison systems nationwide. Twenty-eight prison systems (55%) offer methadone to inmates in some situations. Methadone use varies widely across states: over 50% of correctional facilities that offer methadone do so exclusively for pregnant women or for chronic pain management. Seven states' prison systems (14%) offer buprenorphine to some inmates. The most common reason cited for not offering ORT was that facilities “prefer drug-free detoxification over providing methadone or buprenorphine.” Twenty-three states' prison systems (45%) provide referrals for some inmates to methadone maintenance programs after release, which increased from 8% in 2003; 15 states' prison systems (29%) provide some referrals to community buprenorphine providers. Conclusion Despite demonstrated social, medical, and economic benefits of providing ORT to inmates during incarceration and linkage to ORT upon release, many prison systems nationwide still do not offer pharmacological treatment for opiate addiction or referrals for ORT upon release. PMID:19625142

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Arrhythmia Associated with Buprenorphine and Methadone Reported to the Food and Drug Administration

    PubMed Central

    Kao, David P; Haigney, Mark CP; Mehler, Philip S; Krantz, Mori J

    2015-01-01

    Aim To assess the relative frequency of reporting of adverse events involving ventricular arrhythmia, cardiac arrest, QTc prolongation, or torsade de pointes to the US Food and Drug Administration (FDA) between buprenorphine and methadone. Design Retrospective pharmacoepidemiologic study Setting Adverse drug events spontaneously reported to the FDA between 1969-June 2011 originating in 196 countries (71% events from the US). Cases Adverse event cases mentioning methadone (n=14,915) or buprenorphine (n=7,283) were evaluated against all other adverse event cases (n= 4,796,141). Measurements The primary outcome was the composite of ventricular arrhythmia or cardiac arrest. The secondary outcome was the composite of QTc prolongation or torsade de pointes. The proportional reporting ratio (PRR) was used to identify disproportionate reporting defined as a PRR>2, χ2 error>4, with ≥3 cases. Findings There were 132 (1.8%) ventricular arrhythmia/cardiac arrest and 19 (0.3%) QTc prolongation/torsade de pointes cases associated with buprenorphine compared with 1729 (11.6%) ventricular arrhythmia/cardiac arrest and 390 (2.6%) QTc prolongation/torsade de pointes cases involving methadone. PRRs associated with buprenorphine were not significant for ventricular arrhythmia/cardiac arrest (1.1 95% confidence interval (CI) 0.9–1.3, χ2=1.2) or QTc prolongation/torsade de pointes (1.0 95% CI 0.7–1.9, χ2=0.0006), but were for methadone (7.2 95% CI 6.9–7.5, χ2=9160; 10.6 95% CI 9.7–11.8, χ2=3305, respectively). Conclusion In spontaneously reported adverse events, methadone is associated with disproportionate reporting of cardiac arrhythmias, whereas buprenorphine is not. Although these findings probably reflect clinically relevant differences, a causal connection cannot be presumed and disproportionality analysis cannot quantify absolute risk per treatment episode. Population-based studies to definitively quantify differential incidence rates are warranted. PMID:26075588

  12. 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

  13. 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

  14. 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

  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.

  16. 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

  17. 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%).

  18. 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

  19. 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.

  20. 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

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

    PubMed

    Kosel, Juliusz; Bobik, Piotr; Tomczyk, Michał

    2016-01-01

    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.

  2. 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

  3. Changes in Quality of Life (WHOQOL-BREF) and Addiction Severity Index (ASI) among participants in Opioid Substitution Treatment (OST) in Low and Middle Income Countries: An International Systematic Review

    PubMed Central

    Feelemyer, Jonathan P; Jarlais, Don C Des; Arasteh, Kamyar; Phillips, Benjamin W; Hagan, Holly

    2013-01-01

    Background Opioid substitution treatment (OST) can increase quality of life (WHOQOL-BREF) and reduce addiction severity index (ASI) scores among participants over time. OST program participants have noted that improvement in quality of life is one of the most important variables to their reduction in drug use. However, there is little systematic understanding of WHOQOL-BREF and ASI domain changes among OST participants in low and middle-income countries (LMIC). Methods Utilizing PRISMA guidelines we conducted a systematic literature search to identify OST program studies documenting changes in WHOQOL-BREF or ASI domains for participants in buprenorphine or methadone programs in LMIC. Standardized mean differences for baseline and follow-up domain scores were compared along with relationships between domain scores, OST dosage, and length of follow-up. Results There were 13 OST program studies with 1801 participants from seven countries eligible for inclusion in the review. Overall, statistically significant changes were noted in all four WHOQOL-BREF domain and four of the seven ASI domain scores (drug, psychological, legal, and family) documented in studies. Dosage of pharmacologic medication and length of follow-up did not affect changes in domain scores. Conclusion WHOQOL-BREF and ASI domain scoring is a useful tool in measuring overall quality of life and levels of addiction among OST participants. Coupled with measurements of blood-borne infection, drug use, relapse, and overdose, WHOQOL-BREF and ASI represent equally important tools for evaluating the effects of OST over time and should be further developed as integrated tools in the evaluation of participants in LMIC. PMID:24200104

  4. 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

  5. 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

  6. Stakeholders in opioid substitution treatment policy: similarities and differences in six European countries.

    PubMed

    Thom, Betsy; Duke, Karen; Frank, Vibeke Asmussen; Bjerge, Bagga

    2013-08-01

    Based on the research papers within this special issue, this overview discusses similarities and differences in stakeholding in drug user opioid substitution treatment policy in Britain, Denmark, Italy, Austria, Poland, and Finland. It explores factors that have influenced stakeholder activity, including the importance of crisis, the impact of evidence, the availability of resources, the wider political context, the influence of moral frameworks and ideologies, and the pressure of external influences. The paper highlights the important differences in the emergence and evolution of stakeholder groups and in the political, cultural, and economic circumstances, which both constrain and enable their activities.

  7. Clonazepam as Agonist Substitution Treatment for Benzodiazepine Dependence: A Case Report

    PubMed Central

    Maremmani, Angelo Giovanni Icro; Rovai, Luca; Rugani, Fabio; Bacciardi, Silvia; Pacini, Matteo; Dell'Osso, Liliana; Maremmani, Icro

    2013-01-01

    Nowadays, the misuse of benzodiazepines (BZDs) is a cause for a serious concern among pharmacologically inexperienced patients, whether treated or untreated, that could lead to significant complications, including tolerance, dependence, and addiction. We present a case report in which an Italian patient affected by anxiety disorder and treated with BZDs presented a severe case of dependence on BZDs. We treated him according to an agonist substitution approach, switching from the abused BZD to a slow-onset, long-acting, high potency agonist (clonazepam), and looking at the methadone treatment model as paradigm. We decided to use clonazepam for its pharmacokinetic properties. The advantage of choosing a slow-onset, long-lasting BZD for the treatment of our patient was that it led us to a remarkable improvement in the clinical situation, including the cessation of craving, absence of withdrawal symptoms, reduced anxiety, improvements in social functioning, and a better cognition level. PMID:23424702

  8. In vitro release of clomipramine HCl and buprenorphine HCl from poly adipic anhydride (PAA) and poly trimethylene carbonate (PTMC) blends.

    PubMed

    Dinarvand, Rassoul; Alimorad, Mohammed Massoud; Amanlou, Massoud; Akbari, Hamid

    2005-10-01

    Controlled drug-delivery technology is concerned with the systematic release of a pharmaceutical agent to maintain a therapeutic level of the drug in the body for modulated and/or prolonged periods of time. This may be achieved by incorporating the therapeutic agent into a degradable polymer vehicle, which releases the agent continuously as the matrix erodes. In this study, poly trimethylene carbonate (PTMC), an aliphatic polycarbonate, and poly adipic anhydride (PAA), an aliphatic polyanhydride, were synthesized via melt condensation and ring-opening polymerization of trimethylene carbonate and adipic acid, respectively. The release of clomipramine HCl and buprenorphine HCl from discs prepared with the use of PTMC-PAA blends in phosphate buffer (pH 7.4) are also described. Clomipramine HCl and buprenorphine HCl were both used as hydrophilic drug models. Theoretical treatment of the data with the Peppas model revealed that release of clomipramine HCl (5%) in devices containing 70% PTMC or more followed a Fickian diffusion model. However, the releases of buprenorphine HCl (5%) in the same devices were anomalous. For devices containing 50% and more PAA, surface erosion may play a significant role in the release of both molecules.

  9. Psychomotor effects of ketorolac in comparison with buprenorphine and diclofenac.

    PubMed

    MacDonald, F C; Gough, K J; Nicoll, R A; Dow, R J

    1989-04-01

    1. Ketorolac is an investigational non-opioid analgesic. Buprenorphine, an opioid compound and diclofenac, a non-steroidal anti-inflammatory, are analgesics used in clinical practise. 2. The psychomotor effects of ketorolac (30 mg), buprenorphine (0.3 mg), diclofenac (50 mg) and placebo all administered i.m., were examined in 12 healthy male volunteers (age 19-38 years), up to 8 h post-dose. 3. Creatine phosphokinase (CPK) was measured up to 24 h post-dose, providing an indication of local tissue damage following injection. 4. Buprenorphine caused significant psychomotor impairment in seven out of eight psychomotor tests. The effects consistently peaked 4 h post-dose and were still apparent in many cases 8 h post-dose. These psychomotor effects were supported by marked symptoms in all volunteers. 5. Ketorolac and diclofenac had no clinically significant effects on psychomotor tests and only minimal symptoms were reported. 6. Diclofenac caused a marked increased in CPK (mean Cmax 298 iu l-1) compared with ketorolac (mean Cmax 70 iu l-1) and buprenorphine (mean Cmax 68 iu l-1). 7. These results suggest that ketorolac and diclofenac are suitable for administration following day case surgery. PMID:2785813

  10. [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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. The effect of substitution therapy on symptoms in patients with hypothyroidism following treatment for laryngeal and hypopharyngeal carcinomas.

    PubMed

    Lo Galbo, A M; Verdonck-De Leeuw, I M; Lips, P; Kuik, D J; Leemans, C R; De Bree, R

    2013-08-01

    Hypothyroidism is a well-known complication following treatment of laryngeal or hypopharyngeal carcinomas, and may cause various psychological and physical problems that negatively affect quality of life. The aim of this study was to evaluate the effect of substitution therapy on symptoms in patients with hypothyroidism. A study-specific questionnaire on physical and psychological problems (before and after substitution therapy) was sent to 70 patients who had been treated between 1977 and 2008 with clinical or subclinical hypothyroidism. Ninety-four percent returned the questionnaire. Symptoms on energy levels were reported most often (67% always tired and 70% lack of energy). Moodiness and emotional and physical symptoms were reported more often in substituted (sub)clinical hypothyroidism. Substitution therapy resulted in an improvement of energy (P = 0.013), sense of general interest and enjoyment (P = 0.022) and a reduction of puffy face (P = 0.041). Most symptoms in patients with thyroid dysfunction do not improve after substitution therapy. Nevertheless, due to its impact on health-related quality of life and the low burden of substitution therapy, screening for hypothyroidism and subsequent substitution therapy remains important.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. [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

  7. [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.

  8. Pharmacologic treatments for opioid dependence: detoxification and maintenance options

    PubMed Central

    Kleber, Herbert D.

    2007-01-01

    While opioid dependence has more treatment agents available than other abused drugs, none are curative. They can, however, markedly diminish withdrawal symptoms and craving, and block opioid effects due to lapses. The most effective withdrawal method is substituting and tapering methadone or buprenorphine, α-2 Adrenergic agents can ameliorate untreated symptoms or substitute for agonists if not available. Shortening withdrawal by precipitating it with narcotic antagonists has been studied, but the methods are plagued by safety issues or persisting symptoms. Neither the withdrawal agents nor the methods are associated with better long-term outcome, which appears mostly related to post-detoxification treatment. Excluding those with short-term habits, the best outcome occurs with long-term maintenance on methadone or buprenorphine accompanied by appropriate psychosocial interventions. Those with strong external motivation may do well on the antagonist naltrexone. Currently, optimum duration of maintenance on either is unclear. Better agents are needed to impact the brain changes related to addiction. PMID:18286804

  9. False-positive buprenorphine EIA urine toxicology results due to high dose morphine: a case report.

    PubMed

    Tenore, Peter L

    2012-01-01

    In monitoring a patient with chronic pain who was taking high-dose morphine and oxycodone with weekly urine enzymatic immunoassay (EIA) toxicology testing, the authors noted consistent positives for buprenorphine. The patient was not taking buprenorphine, and gas chromatography/mass spectroscopy (GCMS) testing on multiple samples revealed no buprenorphine, indicating a case of false-positive buprenorphine EIAs in a high-dose opiate case. The authors discontinued oxycodone for a period of time and then discontinued morphine. Urine monitoring with EIAs and GCMS revealed false-positive buprenorphine EIAs, which remained only when the patient was taking morphine. When taking only oxycodone and no morphine, urine samples became buprenorphine negative. When morphine was reintroduced, false-positive buprenorphine results resumed. Medical practitioners should be aware that high-dose morphine (with morphine urine levels turning positive within the 15,000 to 28,000 mg/mL range) may produce false-positive buprenorphine EIAs with standard urine EIA toxicology testing.

  10. False-positive buprenorphine by CEDIA in patients prescribed amisulpride or sulpiride.

    PubMed

    Birch, M A; Couchman, L; Pietromartire, S; Karna, T; Paton, C; McAllister, R; Marsh, A; Flanagan, R J

    2013-05-01

    Buprenorphine is a potent partial opioid agonist that is analyzed in urine to (i) monitor adherence to maintenance or detoxification therapy and (ii) detect illicit use. Buprenorphine analysis is commonly conducted on urine by immunoassay, but is subject to cross-reactivity from other drugs/drug metabolites, including morphine, codeine and dihydrocodeine. This study reports false-positive buprenorphine analysis [Thermo Fisher Scientific cloned enzyme donor immunoassay (CEDIA)] in patients who denied unauthorized buprenorphine use prior to sampling, but who had been prescribed amisulpride. In two cases, confirmatory analysis by liquid chromatography-tandem mass spectrometry was negative (<0.5 µg/L) for buprenorphine and metabolites and positive for amisulpride. Although the cross-reactivity of amisulpride and sulpiride in the CEDIA buprenorphine assay is low (estimated at 0.003 and 0.002%, respectively), it remains a significant consideration given the likely high concentrations of these compounds in urine relative to the low cutoff of the buprenorphine assay. Neither amisulpride nor sulpiride was listed as potential sources of interference on the CEDIA data sheet when this work was performed. These findings highlight the importance of confirming immunoassay-positive buprenorphine results using a more selective analytical technique.

  11. Fulminant hepatic failure after intravenous injection of sublingual buprenorphine in a patient with hepatitis C.

    PubMed

    French, Janine; Mujumdar, Avik; Angus, Peter; Gow, Paul

    2015-08-01

    A 20-year-old indigenous Australian male was admitted to the intensive care unit with fulminant hepatic failure secondary to intravenous use of buprenorphine, which had been prescribed sublingually for opioid dependence. Intravenous buprenorphine-induced hepatitis is well recognized, however, life-threatening fulminant hepatic failure has not previously been reported.

  12. 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

  13. 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

  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. 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

  16. 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

  17. 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

  18. [Experiences with Epigard, a synthetic skin substitute, in the treatment of skin defects].

    PubMed

    Kiffner, E; Bohmert, H

    1976-05-20

    Epigard, a reticulated polyurethane foam laminated to a microporous polypropylene film, has been developed as a substitute for homograft and heterograft skin. After preliminary studies in animals, its clinical advantages and limitations were evaluated in 134 hospitilized patients with burn injuries and other skin defects. Examples for its indications are demonstrated and discussed. It is concluded that Epigard provides a satisfactory substitute for skin grafts with major advantages for ready availability, sterility and reduced cost.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  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. Addition of Dexamethasone and Buprenorphine to Bupivacaine Sciatic Nerve Block: A Randomized, Controlled Trial

    PubMed Central

    YaDeau, Jacques T.; Paroli, Leonardo; Fields, Kara G.; Kahn, Richard L.; LaSala, Vincent R.; Jules-Elysee, Kethy M.; Kim, David H.; Haskins, Stephen C.; Hedden, Jacob; Goon, Amanda; Roberts, Matthew M.; Levine, David S.

    2015-01-01

    Background and Objectives Sciatic nerve block provides analgesia after foot and ankle surgery, but block duration may be insufficient. We hypothesized that perineural dexamethasone and buprenorphine would reduce pain scores at 24 hours. Methods Ninety patients received ultrasound-guided sciatic (25 mL 0.25% bupivacaine) and adductor canal (10 mL 0.25% bupivacaine) blockade, with random assignment into 3 groups (30 patients per group): control blocks + intravenous dexamethasone (4 mg) (control); control blocks + intravenous buprenorphine (150 mcg) + intravenous dexamethasone (intravenous buprenorphine); nerve blocks containing buprenorphine + dexamethasone (perineural). Patients received mepivacaine neuraxial anesthesia and postoperative oxycodone / acetaminophen, meloxicam, pregabalin, and ondansetron. Patients and assessors were blinded to group assignment. The primary outcome was pain with movement at 24 hours. Results There was no difference in pain with movement at 24 hours (median score 0). However, the perineural group had longer block duration vs control (45.6 vs 30.0 hr). Perineural patients had lower scores for “worst pain” vs control (median 0 vs 2). Both intravenous buprenorphine and perineural groups were less likely to use opioids on the day after surgery, vs control (28.6%, 28.6%, 60.7%, respectively). Nausea after intravenous buprenorphine (but not perineural buprenorphine) was severe, frequent, and bothersome. Conclusions Pain scores were very low at 24 hours after surgery in the context of multimodal analgesia and were not improved by additives. However, perineural buprenorphine and dexamethasone prolonged block duration, reduced the worst pain experienced, and reduced opioid use. Intravenous buprenorphine caused troubling nausea and vomiting. Future research is needed to confirm and extend these observations. PMID:25974277

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  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. [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

  17. 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

  18. 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.

  19. Simultaneous quantification of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in human placenta by liquid chromatography mass spectrometry

    PubMed Central

    Concheiro-Guisan, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.

    2011-01-01

    A LCMS method was developed and validated for the determination of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and norbuprenorphine glucuronide (NBUP-Gluc) in placenta. Quantification was achieved by selected ion monitoring of m/z 468.4 (BUP), 414.3 (NBUP), 644.4 (BUP-Gluc), and 590 (NBUP-Gluc). BUP and NBUP were identified monitoring MS2 fragments m/z 396, 414 and 426 for BUP, and 340, 364 and 382 for NBUP, and glucuronide conjugates monitoring MS3 fragments m/z 396 and 414 for BUP-Gluc, and 340 and 382 for NBUP-Gluc. Linearity was 1–50 ng/g. Intra-day, inter-day and total assay imprecision (% RSD) were <13.4%, and analytical recoveries were 96.2–113.1%. Extraction efficiencies ranged from 40.7–68%, process efficiencies 38.8–70.5%, and matrix effect 1.3–15.4%. Limits of detection were 0.8 ng/g for all compounds. An authentic placenta from an opioid-dependent pregnant woman receiving BUP pharmacotherapy was analyzed. BUP was not detected but metabolite concentrations were NBUP-Gluc 46.6, NBUP 15.7 and BUP-Gluc 3.2 ng/g. PMID:19247639

  20. 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

  1. Pharmacokinetics and Antinociceptive Activity of Sustained-Release Buprenorphine in Sheep.

    PubMed

    Walkowiak, Krista J; Graham, Melanie L

    2015-11-01

    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

  2. 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

  3. Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy Greyhound dogs

    PubMed Central

    KuKanich, Butch; Allen, Philip

    2014-01-01

    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 (3 males and 3 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

  4. Quantitative analysis of buprenorphine and norbuprenorphine in urine using liquid chromatography tandem mass spectrometry.

    PubMed

    Fox, E J; Tetlow, V A; Allen, K R

    2006-05-01

    Buprenorphine is an opioid analgesic drug that is used as an alternative to methadone to treat heroin addiction. Established methods for the analysis of buprenorphine and its metabolites in urine such as gas chromatography-mass spectrometry (GC-MS) involve complicated sample extraction procedures. The aim of the present study was to develop a sensitive yet straightforward method for the simultaneous analysis of buprenorphine and norbuprenorphine in urine using liquid chromatography-MS-MS. The method comprised an enzymatic hydrolysis using Patella vulgata b-glucuronidase, followed by centrifugation and direct analysis of the supernatant. The limits of detection and quantitation were < 1 microg/L for buprenorphine and < 1 and 4 microg/L, respectively, for norbuprenorphine. Assay coefficients of variation (CVs) were < 15%, with the exception of concentrations close to the limit of quantitation, where CVs were below 20%. In direct comparison with an established GC-MS protocol, the method showed minimal negative bias (8.7% for buprenorphine and 1.8% for norbuprenorphine) and was less susceptible to sample carryover. The extent of conjugation in unhydrolyzed urine was investigated and found to be highly variable, with proportions of unconjugated buprenorphine and norbuprenorphine of 6.4% [range 0% to 67%; standard deviation (SD) 9.7%] and 34% (range 0% to 100%; SD 23.8%), respectively. PMID:16803661

  5. Plasma buprenorphine concentrations after the application of a 70 microg/h transdermal patch in dogs. Preliminary report.

    PubMed

    Andaluz, A; Moll, X; Ventura, R; Abellán, R; Fresno, L; García, F

    2009-10-01

    The objective of the present study was to evaluate the plasma concentrations and pharmacokinetics of buprenorphine after transdermal application in dogs (n = 4). A 70 microg/h transdermal buprenorphine patch was applied to the ventral abdomen of four healthy beagles. Blood samples were collected through a preplaced jugular catheter before and at 1, 2, 4, 8, 12, 24, 36, 48 and every 6 h until 108 h after the patch application. Plasma buprenorphine concentrations were measured using a (125)I-labelled radioimmunoassay (RIA) assay. No adverse effects were observed in any of the dogs. Concentrations of buprenorphine were detected in plasma after the application of the transdermal buprenorphine patch on the four experimental animals. Buprenorphine plasma concentrations increased during the first 36 h and then remained in the 0.7-1.0 ng/mL range during the study period. A decrease in plasma buprenorphine concentration was not observed during the study. Although analgesia could not be demonstrated the present study shows the ability of buprenorphine transdermal delivery systems developed for human use to deliver measurable concetrations of buprenorphine in dogs.

  6. 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.

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... specified in § 268.40 as the treatment standard, or unless the waste is a D003 reactive cyanide wastewater... prohibited, unless the waste, at the point of generation, or after any bona fide treatment such as cyanide... constituents or cyanide at levels exceeding the constituent-specific treatment standard found in § 268.48;...

  8. Counseling and directly observed medication for primary care buprenorphine/naloxone maintenance: A pilot study

    PubMed Central

    Moore, Brent A.; Barry, Declan T.; Sullivan, Lynn E.; O’Connor, Patrick G.; Cutter, Christopher J.; Schottenfeld, Richard S.; Fiellin, David A.

    2012-01-01

    Objectives Counseling and medication adherence can affect opioid agonist treatment outcomes. We investigated the impact of two counseling intensities and two medication dispensing methods in patients receiving buprenorphine (BUP) in primary care. Methods In a 12-week trial, patients were assigned to Physician Management (PM) with weekly BUP dispensing (n = 28) vs. PM and directly observed, thrice-weekly BUP and cognitive behavioral therapy (PM+DOT/CBT; n = 27) based on therapist availability. Fifteen minute PM visits were provided at entry, after induction and then monthly. CBT was weekly 45-minute sessions provided by trained therapists. Results Treatment groups differed on baseline characteristics of years of opioid use, history of detoxification from opioids, and opioid negative urines during induction. Analyses adjusting for baseline characteristics showed no significant differences between groups on retention or drug use based on self-report or urines. Patient satisfaction was high across conditions, indicating acceptability of CBT counseling with observed medication. The number of CBT sessions attended was significantly associated with improved outcome, and session attendance was associated with a greater abstinence the following week. Conclusions Although the current findings were non-significant, DOT plus individual CBT sessions was feasible and acceptable to patients. Additional research evaluating the independent effect of directly observed medication and CBT counseling is needed. PMID:22614936

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus).

    PubMed

    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.

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. Prenatal buprenorphine versus methadone exposure and neonatal outcomes: systematic review and meta-analysis.

    PubMed

    Brogly, Susan B; Saia, Kelley A; Walley, Alexander Y; Du, Haomo M; Sebastiani, Paola

    2014-10-01

    Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio=0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (-7.23 days, 95% CI: -10.64, -3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (-8.46 days, 95% CI: -14.48, -2.44) and morphine dose lower (-3.60 mg, 95% CI: -7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio=0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices.

  6. Evaluation of buprenorphine hydrochloride Pluronic(®) gel formulation in male C57BL/6NCrl mice.

    PubMed

    Blankenship-Paris, Terry L; Dutton, John W; Goulding, David R; McGee, Christopher A; Kissling, Grace E; Myers, Page H

    2016-09-21

    Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use in mice due to the viscosity of the product and the small dosing volumes needed. This project evaluated an in-house compounded formulation of buprenorphine easily made in the laboratory using pharmaceutical grade products. The release of buprenorphine was evaluated when compounded with two types of hydrogels (Pluronic(®) F-127 and F-68). Mice given buprenorphine in hydrogel (BP) demonstrated higher serum levels of buprenorphine for a longer period of time compared to mice given standard buprenorphine (Bup). However, the rate of decline in serum levels between the groups was similar; thus, it is more likely that the higher buprenorphine concentration seen in the BP group is due to the higher dose of buprenorphine given, rather than a slower release of product. Feed consumption was decreased in both groups one day after dosing; however, there was no difference in body weights. Increased activity in the open field was observed with both buprenorphine formulations, and lipemia was observed in mice given BP which persisted to at least 96 h. Based on our results, we conclude that this formulation did not sustain the release of buprenorphine or eliminate the increased activity commonly seen in mice given buprenorphine. In addition, the lipemia may confound research parameters, especially in cardiac studies and lipid metabolism studies. Therefore, we cannot recommend this formulation for use.

  7. Evaluation of buprenorphine hydrochloride Pluronic(®) gel formulation in male C57BL/6NCrl mice.

    PubMed

    Blankenship-Paris, Terry L; Dutton, John W; Goulding, David R; McGee, Christopher A; Kissling, Grace E; Myers, Page H

    2016-09-21

    Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use in mice due to the viscosity of the product and the small dosing volumes needed. This project evaluated an in-house compounded formulation of buprenorphine easily made in the laboratory using pharmaceutical grade products. The release of buprenorphine was evaluated when compounded with two types of hydrogels (Pluronic(®) F-127 and F-68). Mice given buprenorphine in hydrogel (BP) demonstrated higher serum levels of buprenorphine for a longer period of time compared to mice given standard buprenorphine (Bup). However, the rate of decline in serum levels between the groups was similar; thus, it is more likely that the higher buprenorphine concentration seen in the BP group is due to the higher dose of buprenorphine given, rather than a slower release of product. Feed consumption was decreased in both groups one day after dosing; however, there was no difference in body weights. Increased activity in the open field was observed with both buprenorphine formulations, and lipemia was observed in mice given BP which persisted to at least 96 h. Based on our results, we conclude that this formulation did not sustain the release of buprenorphine or eliminate the increased activity commonly seen in mice given buprenorphine. In addition, the lipemia may confound research parameters, especially in cardiac studies and lipid metabolism studies. Therefore, we cannot recommend this formulation for use. PMID:27654688

  8. 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

  9. 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

  10. 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

  11. 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

  12. 12 CFR 217.36 - Guarantees and credit derivatives: substitution treatment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... treatment. 217.36 Section 217.36 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM CAPITAL ADEQUACY OF BOARD-REGULATED INSTITUTIONS Risk-Weighted Assets-Standardized Approach... is scheduled to fulfil its obligation on the hedged exposure. If a credit risk mitigant has...

  13. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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,...

  14. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 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,...

  15. 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

  16. 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

  17. Cystectomy and substitution enterocystoplasty: alternative primary treatment for T2/3 bladder cancer.

    PubMed

    Holmes, S A; Christmas, T J; Kirby, R S; Hendry, W F

    1992-03-01

    The optimal treatment for invasive bladder cancer remains controversial. Although external beam radiotherapy is able to eradicate the disease in a number of patients, the difficulty is selecting those who will respond. Those who do develop a local recurrence will require a salvage cystectomy combined with urinary diversion. The results of performing cystectomy and bladder reconstruction as a primary procedure are presented and the concept of combining this with chemotherapy as an alternative strategy for the management of bladder cancer is discussed.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. Comparative assessment of cultured skin substitutes and native skin autograft for treatment of full-thickness burns.

    PubMed Central

    Boyce, S T; Goretsky, M J; Greenhalgh, D G; Kagan, R J; Rieman, M T; Warden, G D

    1995-01-01

    OBJECTIVE: Comparison of cultured skin substitutes (CSSs) and split-thickness autograft (STAG) was performed to assess whether the requirement for autologous skin grafts may be reduced in the treatment of massive burns. SUMMARY BACKGROUND DATA: Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been demonstrated to close full-thickness skin wounds in athymic mice and to express normal skin antigens after closure of excised wounds in burn patients. METHODS: Data were collected from 17 patients between days 2 and 14 to determine incidence of exudate, incidence of regrafting, coloration, keratinization, and percentage of site covered by graft (n = 17). Outcome was evaluated on an ordinal scale (0 = worst; 10 = best) beginning at day 14, with primary analyses at 28 days (n = 10) and 1 year (n = 4) for erythema, pigmentation, epithelial blistering, surface roughness, skin suppleness, and raised scar. RESULTS: Sites treated with CSSs had increased incidence of exudate (p = 0.06) and decreased percentage of engraftment (p < 0.05) compared with STAG. Outcome parameters during the first year showed no differences in erythema, blistering, or suppleness. Pigmentation was greater, scar was less raised, but regrafting was more frequent in CSS sites than STAG. No differences in qualitative outcomes were found after 1 year, and antibodies to bovine collagen were not detected in patient sera. CONCLUSIONS: These results suggest that outcome of engrafted CSSs is not different from STAG and that increased incidence of regrafting is related to decreased percentage of initial engraftment. Increased rates of engraftment of CSSs may lead to improved outcome for closure of burn wounds, allow greater availability of materials for grafting, and reduce requirements for donor skin autograft. Images Figure 1. Figure 2. PMID:8526581

  5. 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

  6. Substitute treatment and replacement in chronic kidney disease: peritoneal dialysis, hemodialysis and transplant.

    PubMed

    Treviño-Becerra, Alejandro

    2009-01-01

    Chronic dialysis replacement treatments or renal transplants are instituted when the patient's glomerular filtration rate, measured by 24-h urine endogenous creatinine clearance, is <10-15 ml/mm and, as the The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI), European and Canadian guidelines point out, when one or two of the following complications occur: "uremic toxicity" symptoms, significant fluid retention that does not respond to loop diuretics, hyperkalemia, chronic anemia (hemoglobin <8 g), metabolic acidosis or acute pulmonary edema. In all patients for whom transplant is indicated, a selected live donor must be sought or, in the absence of contraindications, the patient should be registered with the national cadaver donation waiting list. While waiting for the transplant, patients will be on a chronic dialysis program. There is no national registry of patients undergoing chronic dialysis; only indirect data from the Mexican Kidney Foundation and the dialysis industry are available. However, it is estimated that 40,000-50,000 people are under this treatment and the numbers grow by 11% every year. Overall, it is thought that for every patient receiving chronic dialysis, there is one more patient who dies without access to therapy. Hemodialysis units must comply with the Official Hemodialysis Standard and the General Health Council Hemodialysis Unit Quality Assessment Form.

  7. Complex Pattern of Resistance-Associated Substitutions of Hepatitis C Virus after Daclatasvir/Asunaprevir Treatment Failure

    PubMed Central

    Hasebe, Chitomi; Osaki, Yukio; Joko, Kouji; Yagisawa, Hitoshi; Sakita, Shinya; Okushin, Hiroaki; Satou, Takashi; Hisai, Hiroyuki; Abe, Takehiko; Tsuji, Keiji; Tamada, Takashi; Kobashi, Haruhiko; Mitsuda, Akeri; Ide, Yasushi; Ogawa, Chikara; Tsuruta, Syotaro; Takaguchi, Kouichi; Murakawa, Miyako; Asahina, Yasuhiro; Enomoto, Nobuyuki; Izumi, Namiki

    2016-01-01

    Backgrounds & Aims We aimed to clarify the characteristics of resistance-associated substitutions (RASs) after treatment failure with NS5A inhibitor, daclatasvir (DCV) in combination with NS3/4A inhibitor, asunaprevir (ASV), in patients with chronic hepatitis C virus genotype 1b infection. Methods This is a nationwide multicenter study conducted by the Japanese Red Cross Liver Study Group. The sera were obtained from 68 patients with virological failure after 24 weeks of DCV/ASV treatment. RASs in NS5A and NS3 were determined by population sequencing. Results The frequency of signature RASs at position D168 of NS3 was 68%, and at positions L31 and Y93 of NS5A was 79 and 76%, respectively. The frequency of dual signature RASs in NS5A (L31-RAS and Y93-RAS) was 63%. RASs at L28, R30, P32, Q54, P58, and A92 in addition to dual signature RAS were detected in 5, 5, 1, 22, 2, and 0 patients, respectively. In total, triple, quadruple, and quintuple RASs in combination with dual signature RAS were detected in 35, 10, and 1.5% patients, respectively. These RASs were detected in patients without baseline RASs or who prematurely discontinued therapy. Co-existence of D168 RAS in NS3 and L31 and/or Y93 RAS in NS5A was observed in 62% of patients. Conclusion Treatment-emergent RASs after failure with DCV/ASV combination therapy are highly complex in more than 50% of the patients. The identification of complex RAS patterns, which may indicate high levels of resistance to NS5A inhibitors, highlights the need for RAS sequencing when considering re-treatment with regimens including NS5A inhibitors. PMID:27776192

  8. 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

  9. Vitreous Substitutes

    PubMed Central

    Foster, William Joseph

    2008-01-01

    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

  10. Exploring the effect of N-substitution in nor-lobelane on the interaction with VMAT2: discovery of a potential clinical candidate for treatment of methamphetamine abuse.

    PubMed

    Zheng, Guangrong; Horton, David B; Penthala, Narsimha Reddy; Nickell, Justin R; Culver, John P; Deaciuc, Agripina G; Dwoskin, Linda P; Crooks, Peter A

    2013-03-01

    A series of N-substituted lobelane analogues was synthesized and evaluated for their [(3)H]dihydrotetrabenazine binding affinity at the vesicular monoamine transporter and for their inhibition of vesicular [(3)H]dopamine uptake. Compound 19a, which contains an N-1,2(R)-dihydroxypropyl group, had been identified as a potential clinical candidate for the treatment of methamphetamine abuse.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Pharmacodynamic modelling of placebo and buprenorphine effects on event-related potentials in experimental pain.

    PubMed

    Juul, Rasmus V; Foster, David J R; Upton, Richard N; Andresen, Trine; Graversen, Carina; Drewes, Asbjørn M; Christrup, Lona L; Kreilgaard, Mads

    2014-10-01

    The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine in a cross-over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration-effect models were fitted to data using non-linear mixed-effects modelling implemented in NONMEM (V7.2.0.). Pharmacodynamic models were developed to adequately describe both placebo and buprenorphine ERP data. Models predicted significant placebo effects, but did not predict significant effects related to buprenorphine concentration. Models revealed that ERPs varied both between subjects and between study occasions. ERPs were found to be reproducible within subjects and occasions as population variance was found to be eight times higher than the unexplained variances. Between-subject variance accounted for more than 75% of the population variance. In conclusion, pharmacodynamic modelling was successfully implemented to allow for placebo and variability correction in ERP of experimental pain. Improved outcome of ERP studies can be expected if variation between subjects and study occasions can be identified and described.

  16. New insights into the pharmacological chaperone activity of c2-substituted glucoimidazoles for the treatment of Gaucher disease.

    PubMed

    Li, Zhonghua; Li, Tiehai; Dai, Shaoxing; Xie, Xiaoli; Ma, Xiaofeng; Zhao, Wei; Zhang, Weimin; Li, Jing; Wang, Peng George

    2013-07-01

    Mutations in acid β-glucocerebrosidase (GCase) lead to the accumulation of the sphingolipid glucosylceramide, thereby resulting in Gaucher disease (GD). Active-site-specific competitive GCase inhibitors are effective pharmacological chaperones (PCs) that act as folding agents for mutant GCase folding in the endoplasmic reticulum. In this study, we prepared a series of glucoimidazole C2-substituent derivatives, and evaluated their inhibition and PC properties with GCase. A cell-based assay with patient-derived lymphoblasts (N370S or L444P mutations) demonstrated that administration of these compounds can significantly increase GCase activity. Interestingly, the 3,3-dimethyl-N-phenyl-4-amide-1-butyl-substituted moderate inhibitor 11 had the greatest effect on activity: 2.1-fold increase in N370S lymphoblasts at 2.5 μM and 1.2-fold increase in L444P at 0.5 μM following a three-day incubation. Computer docking studies and a protease protection assay were used to elucidate the ligand-enzyme interactions responsible for the chaperone activity of 11. Western blot and immuno-fluorescence assays verified restoration of GCase trafficking to the lysosome. Together, these results indicate that 11 is a promising PC for GD treatment and provide direct evidence of the mechanism of GCase chaperoning. PMID:23775891

  17. 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

  18. 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

  19. Increasing Potential Access to Opioid Agonist Treatment in U.S. Treatment Shortage Areas

    PubMed Central

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

    2015-01-01

    Opioid use disorders are a significant public health problem, affecting over 2 million individuals in the US. Although opioid agonist treatment, predominantly offered in licensed methadone clinics, is both effective and cost-effective, many individuals do not receive it. Buprenorphine, approved in 2002 for prescription by waivered physicians, could improve opioid agonist treatment access for individuals unable or unwilling to receive methadone. We examine the extent to which the geographic distribution of waivered physicians has enhanced potential opioid agonist treatment access, particularly in non-metropolitan areas with fewer methadone clinics. We found that while the approximately 90% of counties classified as methadone clinic shortage areas remained constant, buprenorphine shortage areas fell from 99% of counties in 2002 to 51% in 2011, lowering the US population percentage residing in opioid treatment shortage counties to approximately 10%. The increase in buprenorphine-waivered physicians has dramatically increased potential access to opioid agonist treatment, especially in non-metropolitan counties. PMID:26056209

  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. 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

    2016-04-19

    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

  2. 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.

  3. Exploring the effect of N-substitution in nor-lobelane on the interaction with VMAT2: discovery of a potential clinical candidate for treatment of methamphetamine abuse

    PubMed Central

    Zheng, Guangrong; Horton, David B.; Penthala, Narsimha Reddy; Nickell, Justin R.; Culver, John P.; Deaciuc, Agripina G.; Dwoskin, Linda P.; Crooks, Peter A.

    2013-01-01

    A series of N-substituted lobelane analogues was synthesized and evaluated for their [3H]dihydrotetrabenazine binding affinity at the vesicular monoamine transporter and for their inhibition of vesicular [3H]dopamine uptake. Compound 19a, which contains an N-1,2(R)-dihydroxypropyl group, had been identified as a potential clinical candidate for the treatment of methamphetamine abuse. PMID:23527317

  4. 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

  5. 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

  6. 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

  7. Effects of buprenorphine on responses to social stimuli in healthy adults.

    PubMed

    Bershad, Anya K; Seiden, Jacob A; de Wit, Harriet

    2016-01-01

    In addition to its classical role in mediating responses to pain, the opioid system is strongly implicated in the regulation of social behavior. In young laboratory animals, low doses of opioid analgesic drugs reduce responses to isolation distress and increase play behavior. However, little is known about how opioid drugs affect responses to social stimuli in humans. Here we examined the effects of buprenorphine, a mu-opioid partial agonist and kappa-antagonist, on three dimensions of social processing: (i) responses to simulated social rejection, (ii) attention to emotional facial expressions, and (iii) emotional responses to images with and without social content. Healthy adults (N=36) attended two sessions during which they received either placebo or 0.2mg sublingual buprenorphine in randomized order, under double-blind conditions. Ninety minutes after drug administration, they completed three behavioral tasks: (i) a virtual ball-toss game in which they were first included and then excluded by the other players; (ii) an attention task in which they were shown pairs of faces (one emotional and one neutral), while the direction of their gazes was recorded using electrooculography, and (iii) a picture-viewing task, in which they rated standardized images with and without social content. During the ball-toss game, buprenorphine decreased perceived social rejection. During the attention task, the drug reduced initial attention to fearful facial expressions, without influencing attention to angry, happy, or sad faces. Finally, during the picture-viewing task, buprenorphine increased ratings of positivity of images with social content without affecting ratings of nonsocial images. These results suggest that even at low doses, opioid analgesic drugs reduce responses to some types of negative social stimuli while enhancing positive responses to social stimuli. This provides further support for the role of the opioid system in mediating responses to social rejection and

  8. Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation.

    PubMed

    Jirkof, P; Tourvieille, A; Cinelli, P; Arras, M

    2015-07-01

    Sustained-release formulations of analgesic drugs are promising alternatives to repeated drug injections. Here, we compared a sustained-release formulation of buprenorphine (SB, 2.2 mg/kg) with a standard protocol of three injections of buprenorphine (Temgesic, 0.1 mg/kg/8 h) in mice. Buprenorphine serum concentration and analgesic action (thermal sensitivity) were determined in healthy mice. Additionally, the pain relief properties of both protocols were assessed after laparotomy using physiological and ethological measures of pain and recovery. Serum concentrations and thermal sensitivity tests indicated duration of action of at least 4 h (but less than 8 h) with the Temgesic protocol, and 24-48 h with SB. Behavioural and clinical parameters indicated at least partial pain relief after surgery for both protocols. Observed side-effects of buprenorphine independent of the protocol were increased activity, disturbed circadian rhythm and several abnormal behaviours. A tendency for decreased food and water intake as well as body weight reduction was also seen. Body weight decreased significantly in animals that received three injections of Temgesic, regardless of whether surgery was performed or not (P = 0.015; P = 0.023), hinting at a stress response towards this repeated intervention. In conclusion, an application interval of 8 h (Temgesic) appears too long and might lead to repeated periods with insufficient analgesia in animals undergoing lasting and/or substantial pain after surgery. In comparison to the standard protocol, SB provided a long-lasting, assured analgesia without possible stressful repeated injections in a standard surgical model, with only limited and acceptable behavioural side-effects.

  9. Effects of buprenorphine on responses to social stimuli in healthy adults.

    PubMed

    Bershad, Anya K; Seiden, Jacob A; de Wit, Harriet

    2016-01-01

    In addition to its classical role in mediating responses to pain, the opioid system is strongly implicated in the regulation of social behavior. In young laboratory animals, low doses of opioid analgesic drugs reduce responses to isolation distress and increase play behavior. However, little is known about how opioid drugs affect responses to social stimuli in humans. Here we examined the effects of buprenorphine, a mu-opioid partial agonist and kappa-antagonist, on three dimensions of social processing: (i) responses to simulated social rejection, (ii) attention to emotional facial expressions, and (iii) emotional responses to images with and without social content. Healthy adults (N=36) attended two sessions during which they received either placebo or 0.2mg sublingual buprenorphine in randomized order, under double-blind conditions. Ninety minutes after drug administration, they completed three behavioral tasks: (i) a virtual ball-toss game in which they were first included and then excluded by the other players; (ii) an attention task in which they were shown pairs of faces (one emotional and one neutral), while the direction of their gazes was recorded using electrooculography, and (iii) a picture-viewing task, in which they rated standardized images with and without social content. During the ball-toss game, buprenorphine decreased perceived social rejection. During the attention task, the drug reduced initial attention to fearful facial expressions, without influencing attention to angry, happy, or sad faces. Finally, during the picture-viewing task, buprenorphine increased ratings of positivity of images with social content without affecting ratings of nonsocial images. These results suggest that even at low doses, opioid analgesic drugs reduce responses to some types of negative social stimuli while enhancing positive responses to social stimuli. This provides further support for the role of the opioid system in mediating responses to social rejection and

  10. Determination of buprenorphine, fentanyl and LSD in whole blood by UPLC-MS-MS.

    PubMed

    Berg, Thomas; Jørgenrud, Benedicte; Strand, Dag Helge

    2013-04-01

    A sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method has been developed and validated for the quantification of buprenorphine, fentanyl and lysergic acid diethylamide (LSD) in whole blood. Sample preparation was performed by liquid-liquid extraction (LLE) with methyl tert-butyl ether. UPLC-MS-MS analysis was performed with a mobile phase consisting of ammonium formate (pH 10.2) and methanol. Positive electrospray ionization MS-MS detection was performed with two multiple reaction monitoring transitions for each of the analytes and the deuterium labeled internal standards. Limit of detection values of buprenorphine, fentanyl and LSD were 0.28, 0.044 and 0.0097 ng/mL and limit of quantification values were 0.94, 0.14 and 0.036 ng/mL, respectively. Most phospholipids were removed during LLE. No or only minor matrix effects were observed. The method has been routinely used at the Norwegian Institute of Public Health since September 2011 for qualitative and quantitative detections of buprenorphine, fentanyl and/or LSD in more than 400 whole blood samples with two replicates per sample.

  11. Oral buprenorphine is anti-inflammatory and modulates the pathogenesis of streptococcal cell wall polymer-induced arthritis in the Lew/SSN rat.

    PubMed

    Volker, D; Bate, M; Gentle, R; Garg, M

    2000-10-01

    This study was carried out to determine an effective regimen for pain management in streptococcal cell wall (SCW)-induced arthritis in female Lew/SSN rats. Forty weanling rats lin 2 groups) were trained to accept disks of jelly as part of their dietary regimen. At 8 weeks of age weighing 150 g, SCW arthritis was induced and sublingual buprenorphine tablets were incorporated into the jelly disks to alleviate the pain of acute arthritis, which developed 24 h post-induction. Group A rats received buprenorphine at a rate of 1 mg/kg 12 hourly. Group B rats received buprenorphine at a rate of 2 mg/kg 12 hourly. Both groups of rats were monitored for symptoms of distress using an adaptation of the Morton and Griffin scale of adverse reactions. Group A rats with severe arthritis required additional subcutaneous (s.c.) injections of buprenorphine to alleviate the adverse effects of arthritis. Group B rats, with twice the dose of buprenorphine did not require additional s.c. injections of buprenorphine. Histological sections of rat hocks indicated that the inflammation was suppressed in Group B rats. We concluded that oral administration of buprenorphine is an effective method of pain management in the pathogenesis of SCW-induced arthritis in Lew/SSN rats. In this model of arthritis, oral buprenorphine has a significant anti-inflammatory effect and appears to modulate the destructive arthritic phase in joints in this animal model of arthritis.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. Hemoglobin substitutes.

    PubMed

    Anbari, Kevin K; Garino, Jonathan P; Mackenzie, Colin F

    2004-10-01

    Orthopaedic patients frequently require blood transfusions to treat peri-operative anemia. Research in the area of hemoglobin substitutes has been of great interest since it holds the promise of reducing the reliance on allogeneic blood transfusions. The three categories of hemoglobin substitutes are (1) cell-free, extracellular hemoglobin preparations made from human or bovine hemoglobin (hemoglobin-based oxygen carriers or HBOCs); (2) fluorine-substituted linear or cyclic carbon chains with a high oxygen-carrying capacity (perfluorocarbons); and (3) liposome-encapsulated hemoglobin. Of the three, HBOCs have been the most extensively studied and tested in preclinical and clinical trials that have shown success in diminishing the number of blood transfusions as well as an overall favorable side-effect profile. This has been demonstrated in vascular, cardiothoracic, and orthopaedic patients. HBOC-201, which is a preparation of cell-free bovine hemoglobin, has been approved for clinical use in South Africa. These products may well become an important tool for physicians treating peri-operative anemia in orthopaedic patients.

  18. Simultaneous Quantification of Buprenorphine, Norbuprenorphine, Buprenorphine-Glucuronide and Norbuprenorphine-Glucuronide in Human Umbilical Cord by Liquid Chromatography Tandem Mass Spectrometry

    PubMed Central

    Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.

    2009-01-01

    A LCMS method was developed and validated for the simultaneous determination of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc) and norbuprenorphine glucuronide (NBUP-Gluc) in human umbilical cord. Quantification was achieved by selected ion monitoring of precursor ions m/z 468.4 for BUP; 414.3 for NBUP; 644.4 for BUP-Gluc and 590 for NBUP-Gluc. BUP and NBUP were identified by MS2, with m/z 396, 414 and 426 for BUP, and m/z 340, 364 and 382 for NBUP. Glucuronide conjugates were identified by MS3 with m/z 396 and 414 for BUP-Gluc and m/z 340 and 382 for NBUP-Gluc. The assay was linear 1–50 ng/g. Intra, inter-day and total assay imprecision (%RSD) were <14.5%, and analytical recovery ranged from 94.1% to 112.3% for all analytes. Extraction efficiencies were >66.3%, and process efficiency >73.4%. Matrix effect ranged, in absolute value, from 3.7% to 27.4% (CV<21.8%, n=8). The method was selective with no endogenous or exogenous interferences from 41 compounds evaluated. Sensitivity was high with limits of detection of 0.8 ng/g. In order to prove method applicability, an authentic umbilical cord obtained from an opioid-dependent pregnant woman receiving BUP pharmacotherapy was analyzed. Interestingly, BUP was not detected but concentrations of the other metabolites were NBUP-Gluc 13.4 ng/g, BUP-Gluc 3.5 ng/g and NBUP 1.2 ng/g. PMID:19406593

  19. 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

  20. 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=0.93 μM which represents a 50 fold improvement over the clinical antiandrogen bicalutamide (IC50=46 μM) and a more than 30 fold improvement over enzalutamide (IC50=32 μM). Interestingly, this compound showed even better activity against the human breast cancer cell line (MCF-7); IC50=0.47 μM. Molecular modelling studies provided a plausible theoretical explanation for our findings. PMID:26965862

  1. 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

  2. Environmental assessment of nutrient recycling from biological pig slurry treatment--impact of fertilizer substitution and field emissions.

    PubMed

    Brockmann, Doris; Hanhoun, Mary; Négri, Ophélie; Hélias, Arnaud

    2014-07-01

    Pig slurry treatment is an important means in reducing nitrogen loads applied to farmland. Solid phase separation prior to biological treatment further allows for recovering phosphorus with the solid phase. The organic residues from the pig slurry treatment can be applied as organic fertilizers to farmland replacing mineral fertilizers. The environmental impacts of nutrient recycling from aerobic, biological pig slurry treatment were evaluated applying the life cycle assessment (LCA) methodology. LCA results revealed that direct field emissions from organic fertilizer application and the amount of avoided mineral fertilizers dominated the environmental impacts. A modified plant available nitrogen calculation (PAN) was introduced taking into account calculated nitrogen emissions from organic fertilizer application. Additionally, an equation for calculating the quantity of avoided mineral fertilizers based on the modified PAN calculation was proposed, which accounted for nitrogen emissions from mineral fertilizer application.

  3. Determination of buprenorphine and norbuprenorphine in whole blood by liquid chromatography-mass spectrometry.

    PubMed

    Hoja, H; Marquet, P; Verneuil, B; Lotfi, H; Dupuy, J L; Lachâtre, G

    1997-01-01

    A sensitive and highly specific method for the determination of buprenorphine and norbuprenorphine in postmortem and hemolyzed whole blood using combined liquid chromatography and mass spectrometry (LC-MS) with electrospray ionization was developed. After enzymatic hydrolysis and deproteinization with acetonitrile, Extrelut-3 cartridges were used for a preliminary basic sample cleanup. Elution by toluene-ether (50:50, v/v) was followed by an acid wash with 0.05M H3PO4 and a basic re-extraction into ether. A Nucleosil C18 (150 x 1-mm i.d.) reversed-phase column was used for the chromatographic separation together with a mixture of 2mM ammonium formate buffer (pH 3) and acetonitrile (55:45, v/v) as the mobile phase. Recoveries were between 56 and 60%, and detection limits were 0.05 ng/mL for both analytes. The coefficient of variation for repeatability was lower than 4%. Limits of quantitation were 0.1 ng/mL for buprenorphine and norbuprenorphine. Reproducibility was good, and linearity was excellent in the range of 0.1 to 100 ng/mL (r > 0.9999, n = 7). PMID:9083835

  4. 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

  5. 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

  6. The substitution of sand filtration by immersed-UF for surface water treatment: pilot-scale studies.

    PubMed

    Lihua, Sun; Xing, Li; Guoyu, Zhang; Jie, Chen; Zhe, Xu; Guibai, Li

    2009-01-01

    The newly issued National Drinking Water Standard required that turbidity should be lower than 1 NTU, and the substitution of sand filtration by immersed ultrafiltration (immersed-UF) is feasible to achieve the standard. This study aimed to optimise the operational processes (i.e. aeration, backwashing) through pilot scale studies, to control membrane fouling while treating the sedimentation effluent. Results indicated that the immersed-UF was promising to treat the sedimentation effluent. The turbidity was below 0.10 NTU, bacteria and E. coli were not detected in the permeate water. The intermittent filtration with aeration is beneficial to inhibit membrane fouling. The critical aeration intensity is observed to be 60.0 m(3) m(-2) h(-1). At this aeration intensity, the decline rate of permeate flux in one period of backwashing was 1.94% and 7.03% for intermittent filtration and sustained filtration respectively. The different membrane backwashing methods (i.e. aeration 1.5 min, synchronous aeration and water backwashing 2 min, water backwashing 1.5 min; synchronous aeration and water backwashing 3 min, water backwashing 2 min; aeration 3 min, single water backwashing 2 min; synchronous aeration and water backwashing 5 min; single water backwashing 5 min) on the recovery of permeate flux were compared, indicating that the synchronous aeration and water backwashing exhibited best potential for permeate flux recovery. The optimal intensity of water backwashing is shown to be 90.0 L m(-2) h(-1). When the actual water intensity was below or exceeded the value, the recovery rate of permeate flux would be reduced. Additionally, the average operating cost for the immersed UF membrane, including the power, the chemical cleaning reagents, and membrane modules replacement, was about 0.31 RMB/m(3).

  7. 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

  8. Blood substitutes.

    PubMed

    Palmer, Andre F; Intaglietta, Marcos

    2014-07-11

    The toxic side effects of early generations of red blood cell substitutes have stimulated development of more safe and efficacious high-molecular-weight polymerized hemoglobins, poly(ethylene glycol)-conjugated hemoglobins, and vesicle-encapsulated hemoglobins. Unfortunately, the high colloid osmotic pressure and blood plasma viscosity of these new-generation materials limit their application to blood concentrations that, in general, are not sufficient for full restoration of oxygen-carrying and -delivery capacity. However, these materials may serve as oxygen therapeutics for treating tissues affected by ischemia and trauma, particularly when the therapeutics are coformulated with antioxidants. These new oxygen therapeutics also possess additional beneficial effects owing to their optimal plasma expansion properties, which induce systemic supraperfusion that increases endothelial nitric oxide production and improves tissue washout of metabolic wastes, further contributing to their therapeutic role.

  9. 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 Central

    Perlman, David C.; Jordan, Ashly E.; Uuskula, Anneli; Huong, Duong Thi; Masson, Carmen L.; Schackman, Bruce R.; Des Jarlais, Don C.

    2015-01-01

    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

  10. 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.

  11. Substance abuse treatment organizations as mediators of social policy: slowing the adoption of a congressionally approved medication.

    PubMed

    Wallack, Stanley S; Thomas, Cindy Parks; Martin, Timothy C; Chilingerian, Jon; Reif, Sharon

    2010-01-01

    Most substance abuse treatment occurs in outpatient treatment centers, necessitating an understanding of what motivates organizations to adopt new treatment modalities. Tichy's framework of organizations as being comprised of three intertwined internal systems (technical, cultural, and political) was used to explain treatment organizations' slow adoption of buprenorphine, a new medication for opiate dependence. Primary data were collected from substance abuse treatment organizations in four of the ten metropolitan areas with the largest number of heroin users. Only about one fifth offered buprenorphine. All three internal systems were important determinants of buprenorphine adoption in our multivariate model. However, the cultural system, measured by attitude toward medications, was a necessary condition for adoption. Health policies designed to encourage adoption of evidence-based performance measures typically focus on the technical system of organizations. These findings suggest that such policies would be more effective if they incorporate an understanding of all three internal systems.

  12. 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

  13. Analysis of buprenorphine in rat plasma using a solid-phase extraction technique and high-performance liquid chromatography with electrochemical detection.

    PubMed

    Salem, A; Pierce, T L; Hope, W

    1997-03-01

    A solid-phase extraction method and sensitive reversed phase high-performance liquid chromatography analysis with electrochemical detection of buprenorphine and its metabolite, norbuprenorphine, in rat plasma is described. Adequate separation of the compounds of interest was achieved on a Phenomenex C18 reversed-phase column using a mobile phase comprising phosphate buffer: acetonitrile (75:25, pH 3.0) and 0.25 mM 1-octane-sulfonic acid, at a flow rat of 1 ml/min. Electrochemical detection was performed at a potential of 0.75 V and sensitivity of 2 nA. Buprenorphine and norbuprenorphine were extracted from plasma by solid-phase extraction technique using naltrindole as an internal standard (IS). Recoveries of buprenorphine and norbuprenorphine following the extraction method were high (70%-89%) over the concentration range used (25-100 ng/ml) and no endogenous substances in plasma interfered with any of the sample components. The retention times for norbuprenorphine, IS, and buprenorphine were 8, 12.5, and 30.5 min, respectively. The limits of detection of buprenorphine and norbuprenorphine in spiked plasma samples were 25 and 5 ng/ml, respectively. Using this method, buprenorphine was detected in rat plasma in animals acutely treated with the drug (5 mg/kg, s.c.).

  14. 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

  15. 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

  16. Simple, heart-smart substitutions

    MedlinePlus

    Coronary artery disease - heart smart substitutions; Atherosclerosis - heart smart substitutions; Cholesterol - heart smart substitutions; Coronary heart disease - heart smart substitutions; Healthy diet - heart ...

  17. 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

  18. Treatment of substituted phenol mixtures in single phase and two-phase solid-liquid partitioning bioreactors.

    PubMed

    Tomei, M Concetta; Rita, Sara; Angelucci, Domenica Mosca; Annesini, M Cristina; Daugulis, Andrew J

    2011-07-15

    The biological treatment of phenolics is constrained by the inherent cytotoxicity of these compounds. One method to alleviate such toxicity is to add a sequestering phase to absorb, and subsequently release, the substrate(s) to the micro-organisms; such a system is termed a Two Phase Partitioning Bioreactor. Here we have compared the performance of a TPPB, relative to single phase operation, in which a small volume (5%, v/v) of beads of the polymer Hytrel 8206 was used to treat aqueous mixtures of 2,4-dimethylphenol and 4-nitrophenol. Hytrel 8206 was selected from a range of polymers that were tested for their partition coefficients (PCs) for the target molecules, with the more hydrophobic compound (2,4-dimethylphenol) having a higher PC value (201) than 4-nitrophenol (143). Significantly increased removal rates for both substrates were demonstrated in TPPB mode relative to single phase operation. Additionally, the differential release of the compounds to the aqueous phase and their distinct PC values changed the kinetic pattern of the biotreatment system, smoothing out the cellular oxygen demand. Release of the substrates by the polymer over 60 operating cycles was virtually complete (>97%) demonstrating the reusability and robustness of the use of polymers in overcoming cytotoxicity of phenolic substrates.

  19. Magnesium substitution in brushite cements: Efficacy of a new biomaterial loaded with vancomycin for the treatment of Staphylococcus aureus infections.

    PubMed

    Cabrejos-Azama, Jatsue; Alkhraisat, Mohammad Hamdan; Rueda, Carmen; Torres, Jesús; Pintado, Concepción; Blanco, Luis; López-Cabarcos, Enrique

    2016-04-01

    Staphylococcus aureus is the most relevant pathogen associated with bone infection that sometimes appears after implant surgery, thus compromising a successful treatment. The aim of this work was to assess the effectiveness of brushite cements, doped with magnesium, as a new vancomycin carrier system against S.aureus infections. We performed an "in vitro" study to evaluate vancomycin release from the cements by measuring its antimicrobial activity against a strain of S.aureus. We have used two methods to load the cements with vancomycin: i) adsorption from a solution and ii) incorporation of the antibiotic into the solid phase during the cement synthesis. Furthermore, the compression strength of the loaded samples was measured to detect changes in the mechanical properties of the system. The "in vitro" study showed that the sustained release of vancomycin depends on the concentration of magnesium in the cement matrix. In addition, the standardized antibacterial assay revealed that the release of vancomycin from the cements may be helpful to prevent infections in bone regeneration procedures.

  20. Efficacy of Sustained-Release Buprenorphine in an Experimental Laparotomy Model in Female Mice.

    PubMed

    Kendall, Lon V; Wegenast, Daniel J; Smith, Brian J; Dorsey, Kathryn M; Kang, Sooah; Lee, Na Young; Hess, Ann M

    2016-01-01

    Mice purportedly require dosing with the opioid buprenorphine (Bup-HCl) at least every 8 to 12 h to maintain an adequate plane of analgesia. Here we used an experimental laparotomy model to determine the clinical efficacy of sustained-release formulations of buprenorphine (Bup-SR) after surgery in mice. Female CD1 mice underwent laparotomy and received either Bup-SR (0.6 mg/kg), Bup-HCl (0.1 mg/kg every 12 h), or saline (every 12 h). Pain was assessed at 1, 3, 6, 12, 24, 48, and 72 h according to the frequency of several behaviors (general activity, wheel-running activity, rearing, grooming, wound licking, orbital tightening, and percentage of integrated nest material) and daily body weight. Over time, wheel running was increased and wound licking was decreased in Bup-SR-treated mice compared with Bup-HCl- and saline-treated mice. Compared with Bup-HCl- and saline-treated mice, Bup-SR-treated mice had increased general activity and percentage of integrated nest material and decreased orbital tightening for 1 to 6 h after surgery. The Bup-HCl- and saline-treated mice had similar general activity, orbital tightening scores, and wheel running activity. Rearing activity and body weight did not differ throughout the study, and none of the observed behaviors differed between groups at 24, 48, and 72 h after surgery. These results suggest that Bup-SR at 0.6 mg/kg provides adequate analgesia after laparotomy in mice and can be used as an alternative analgesic in this context. Furthermore, Bup-HCl at 0.1 mg/kg every 12 h may be inadequate in providing analgesia for abdominal procedures in mice.

  1. Efficacy of Sustained-Release Buprenorphine in an Experimental Laparotomy Model in Female Mice

    PubMed Central

    Kendall, Lon V; Wegenast, Daniel J; Smith, Brian J; Dorsey, Kathryn M; Kang, Sooah; Lee, Na Young; Hess, Ann M

    2016-01-01

    Mice purportedly require dosing with the opioid buprenorphine (Bup-HCl) at least every 8 to 12 h to maintain an adequate plane of analgesia. Here we used an experimental laparotomy model to determine the clinical efficacy of sustained-release formulations of buprenorphine (Bup-SR) after surgery in mice. Female CD1 mice underwent laparotomy and received either Bup-SR (0.6 mg/kg), Bup-HCl (0.1 mg/kg every 12 h), or saline (every 12 h). Pain was assessed at 1, 3, 6, 12, 24, 48, and 72 h according to the frequency of several behaviors (general activity, wheel-running activity, rearing, grooming, wound licking, orbital tightening, and percentage of integrated nest material) and daily body weight. Over time, wheel running was increased and wound licking was decreased in Bup-SR–treated mice compared with Bup-HCl– and saline-treated mice. Compared with Bup-HCl– and saline-treated mice, Bup-SR–treated mice had increased general activity and percentage of integrated nest material and decreased orbital tightening for 1 to 6 h after surgery. The Bup-HCl– and saline-treated mice had similar general activity, orbital tightening scores, and wheel running activity. Rearing activity and body weight did not differ throughout the study, and none of the observed behaviors differed between groups at 24, 48, and 72 h after surgery. These results suggest that Bup-SR at 0.6 mg/kg provides adequate analgesia after laparotomy in mice and can be used as an alternative analgesic in this context. Furthermore, Bup-HCl at 0.1 mg/kg every 12 h may be inadequate in providing analgesia for abdominal procedures in mice. PMID:26817982

  2. Morphine intake and the effects of naltrexone and buprenorphine on the acquisition of methamphetamine intake.

    PubMed

    Eastwood, E C; Phillips, T J

    2014-02-01

    Some common genetic factors appear to influence risk for drug dependence across multiple drugs of abuse. In previous research, mice that were selectively bred for higher amounts of methamphetamine consumption, using a two-bottle choice methamphetamine drinking procedure, were found to be less sensitive to the locomotor stimulant effects of morphine and of the more selective μ-opioid receptor agonist fentanyl, compared to mice that were bred for low methamphetamine consumption. This suggested that μ-opioid receptor-mediated pathways may influence genetic risk for methamphetamine consumption. We hypothesized that these differences in opioid sensitivity would impact opioid intake in the methamphetamine drinking lines and that drugs with μ-opioid receptor activity would impact methamphetamine intake. Consumption of morphine was examined in 2, two-bottle choice studies, one that compared morphine to quinine consumption and another that used a saccharin fading procedure. Next, naltrexone (0, 0.5, 1, 2, 5, 10 and 20 mg/kg), a μ-opioid receptor antagonist, and buprenorphine (0, 1, 2 or 4 mg/kg), a μ-opioid receptor partial agonist, were each examined for their effects on the acquisition of methamphetamine consumption. Low methamphetamine drinking mice consumed more morphine compared to high methamphetamine drinking mice. Naltrexone did not alter methamphetamine consumption in either selected line; however, buprenorphine reduced methamphetamine intake in the high methamphetamine drinking line. These data show that greater sensitivity to opioids is associated with greater opioid intake and warrant further investigation of drugs with μ-opioid receptor-specific agonist activity in genetically determined differences in methamphetamine consumption.

  3. The Effects of Opioid Substitution Treatment and Highly Active Antiretroviral Therapy on the Cause-Specific Risk of Mortality Among HIV-Positive People Who Inject Drugs

    PubMed Central

    Nosyk, Bohdan; Min, Jeong E.; Evans, Elizabeth; Li, Libo; Liu, Lei; Lima, Viviane D.; Wood, Evan; Montaner, Julio S. G.

    2015-01-01

    Background. Prior studies indicated opioid substitution treatment (OST) reduces mortality risk and improves the odds of accessing highly active antiretroviral therapy (HAART); however, the relative effects of these treatments for human immunodeficiency virus (HIV)–positive people who inject drugs (PWID) are unclear. We determine the independent and joint effects of OST and HAART on mortality, by cause, within a population of HIV-positive PWID initiating HAART. Methods. Using a linked population-level database for British Columbia, Canada, we used time-to-event analytic methods, including competing risks models, proportional hazards models with time-varying covariates, and marginal structural models, to identify the independent and joint effects of OST and HAART on all-cause as well as drug- and HIV-related mortality, controlling for covariates. Results. Among 1727 HIV-positive PWID, 493 (28.5%) died during a median 5.1 years (interquartile range, 2.1–9.1) of follow-up: 18.7% due to drug-related causes, 55.8% due to HIV-related causes, and 25.6% due to other causes. Standardized mortality ratios were 12.2 (95% confidence interval [CI], 9.8, 15.0) during OST and 30.0 (27.1, 33.1) during periods out of OST. Both OST (adjusted hazard, 0.34; 95% CI, .23, .49) and HAART (0.39 [0.31, 0.48]) decreased the hazard of all-cause mortality; however, individuals were at lowest risk of death when these medications were used jointly (0.16 [0.10, 0.26]). Both OST and HAART independently protected against HIV-related death, drug-related death and death due to other causes. Conclusions. While both OST and HAART are life-saving treatments, joint administration is urgently needed to protect against both drug- and HIV-related mortality. PMID:26113656

  4. Determination of an optimal dose of medetomidine-ketamine-buprenorphine for anaesthesia in the Cape ground squirrel (Xerus inauris).

    PubMed

    Jouber, K E; Serfontein, T; Scantlebury, M; Manjerovice, M B; Bateman, P W; Bennett, N C; Waterman, J M

    2011-06-01

    The optimal dose of medetomidine-ketamine-buprenorphine was determined in 25 Cape ground squirrels (Xerus inauris) undergoing surgical implantation of a temperature logger into the abdominal cavity. At the end of anaesthesia, the squirrels were given atipamezole intramuscularly to reverse the effects of medetomidine. The mean dose of medetomidine was 67.6 +/- 9.2microg/kg, ketamine 13.6 +/- 1.9 mg/kg and buprenorphine 0.5 +/- 0.06 microg/kg. Induction time was 3.1 +/- 1.4 min. This produced surgical anaesthesia for 21 +/- 4.2 min. Atipamezole 232 +/- 92 microg/kg produced a rapid recovery. Squirrels were sternally recumbent in 3.5 +/- 2.2 min.

  5. 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

  6. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).

    PubMed

    Pergolizzi, Joseph; Böger, Rainer H; Budd, Keith; Dahan, Albert; Erdine, Serdar; Hans, Guy; Kress, Hans-Georg; Langford, Richard; Likar, Rudolf; Raffa, Robert B; Sacerdote, Paola

    2008-01-01

    SUMMARY OF CONSENSUS: 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities--including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia--and patient functional

  7. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).

    PubMed

    Pergolizzi, Joseph; Böger, Rainer H; Budd, Keith; Dahan, Albert; Erdine, Serdar; Hans, Guy; Kress, Hans-Georg; Langford, Richard; Likar, Rudolf; Raffa, Robert B; Sacerdote, Paola

    2008-01-01

    SUMMARY OF CONSENSUS: 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities--including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia--and patient functional

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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)

  15. Buprenorphine medication versus voucher contingencies in promoting abstinence from opioids and cocaine.

    PubMed

    Chopra, Mohit P; Landes, Reid D; Gatchalian, Kirstin M; Jackson, Lisa C; Buchhalter, August R; Stitzer, Maxine L; Marsch, Lisa A; Bickel, Warren K

    2009-08-01

    During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030), while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies.

  16. Buprenorphine medication versus voucher contingencies in promoting abstinence from opioids and cocaine.

    PubMed

    Chopra, Mohit P; Landes, Reid D; Gatchalian, Kirstin M; Jackson, Lisa C; Buchhalter, August R; Stitzer, Maxine L; Marsch, Lisa A; Bickel, Warren K

    2009-08-01

    During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030), while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies. PMID:19653788

  17. Heat treatment effects on structural and dielectric properties of Mn substituted CuFe2O4 and ZnFe2O4 nanoparticles

    NASA Astrophysics Data System (ADS)

    Ranjith Kumar, E.; Arunkumar, T.; Prakash, T.

    2015-09-01

    Manganese substituted copper and zinc ferrite nanoparticles were synthesized by an auto-combustion technique using metal nitrates and urea. The nanoparticles were characterized by XRD, SEM, EDX, and TEM techniques. The effect of annealing temperature on structural and dielectric properties of Mn substituted spinel ferrite nanoparticles was analyzed. The presenting elements in the prepared samples are recorded by EDX. TEM analysis clearly showed the particles are in the nanometer range. The dielectric loss and dielectric constant have been measured in the frequency range of 100 kHz-5 MHz. The variation in structural and dielectric properties of the prepared and annealed samples are discussed.

  18. A behavioral intervention for improving verbal behaviors of heroin addicts in a treatment clinic.

    PubMed

    Petry, N M; Bickel, W K; Tzanis, E; Taylor, R; Kubik, E; Foster, M; Hughes, M E

    1998-01-01

    Positively reinforcing appropriate behaviors improved verbal behaviors of opioid-dependent patients in a buprenorphine treatment clinic. During B phases of an ABAB design, clients received stickers for engaging in appropriate verbal or nonverbal behaviors. Each sticker provided a chance of winning $25. No reinforcement was provided during the A phases. Appropriate verbal behaviors increased during reinforcement periods, and inappropriate verbal behaviors decreased.

  19. 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

  20. Buprenorphine for postoperative analgesia: Axillary brachial plexus block versus intramuscular administration in a placebo-controlled trial

    PubMed Central

    Thakur, Deepali; Malde, Anila

    2015-01-01

    Background and Aims: Peripheral administration of opioids has been suggested for prolongation of regional analgesia. This prospective, randomized, double-blind placebo-controlled study was undertaken to compare the effect of regional (axillary brachial plexus block [ABPB]) versus intramuscular (IM) buprenorphine (2 μg/kg) in adults. Material and Methods: Seventy-five adults undergoing upper limb surgery received ABPB with local anaesthetic (15 ml 0.5% bupivacaine, 15 ml 2% lignocaine with adrenaline 1:200,000, 9 ml normal saline [NS]). In addition, regional group RB (n = 25) received buprenorphine 2 μg/kg in ABPB and 1 ml NS IM. Systemic Group SB (n = 25) received 1 ml NS in ABPB and buprenorphine 2 μg/kg IM. Group C (n = 25) received 1 ml NS in ABPB and IM. Onset, duration of sensory and motor block, hemodynamic parameters, sedation score, pain scores using visual analog scale, duration of postoperative analgesia, rescue analgesic (RA) requirement, adverse events, and patient satisfaction were noted. Results: Demographics, onset and duration of sensory, motor block were similar. RB group had longest duration of analgesia (20.61 ± 1.33 h) compared to SB (10.91 ± 0.90 h) and control group (5.86 ± 0.57 h) (P < 0.05 RB vs. SB/C and SB vs. C). RA requirement was highest in the control group and least in RB group (P = 0.000 RB vs. SB/C and SB vs. C). SB group had a maximum number of side effects (P = 0.041, SB vs. RB/C). Patient satisfaction was highest with group RB (P < 0.05 RB vs. SB/C, and P = 0.06 SB vs. C). Conclusion: Buprenorphine 2 μg/kg in axillary plexus block provides significantly prolonged analgesia with less RA requirement and greater patient satisfaction compared to IM administration. This is highly suggestive of action on peripheral opioid receptors. PMID:26330716

  1. 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…

  2. 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…

  3. 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 that psychological stressors can increase drug craving but not that stressors alter drug seeking. Objectives This clinical study tested whether yohimbine increases opioid seeking behavior. Methods Ten heroin-dependent, buprenorphine (8-mg/day) stabilized volunteers, sampled two doses of hydromorphone (12 and 24 mg IM in counterbalanced order, labeled Drug A [session 1] and Drug B [session 2]). During each of six later sessions (within-subject, double blind, randomized crossover design), volunteers could respond on a 12-trial choice progressive ratio task to earn units (1 or 2 mg) of the sampled hydromorphone dose (Drug A or B) vs. money ($2) following different oral yohimbine pretreatment doses (0, 16.2 and 32.4 mg). Results Behavioral economic demand intensity and peak responding (Omax) were significantly higher for hydromorphone 2-mg than 1-mg. Relative to placebo, yohimbine significantly increased hydromorphone demand inelasticity, more so for hydromorphone 1-mg units (Pmax = 909, 3647 and 3225 for placebo, 16.2 and 32.4 mg yohimbine doses, respectively) than hydromorphone 2-mg units (Pmax = 2656, 3193 and 3615, respectively). Yohimbine produced significant but clinically modest dose-dependent increases in blood pressure (systolic ≈15 and diastolic ≈10 mmHg) and opioid withdrawal symptoms, and decreased opioid agonist symptoms and elated mood. Conclusions These findings concur with preclinical data by demonstrating that yohimbine increases drug seeking; in this study, these effects occurred without clinically significant subjective distress or elevated craving, and partly depended on opioid unit dose. PMID:23161001

  4. Medically assisted recovery from opiate dependence within the context of the UK drug strategy: methadone and Suboxone (buprenorphine-naloxone) patients compared.

    PubMed

    McKeganey, Neil; Russell, Christopher; Cockayne, Lucinda

    2013-01-01

    The focus of drug policy in the UK has shifted markedly in the past 5 years to move beyond merely emphasising drug abstinence towards maximising individuals' opportunities for recovery. The UK government continues to recognise the prescribing of narcotic medications indicated for opiate dependence as a key element of these individuals' recovery journey. This article describes a small, naturalistic comparison of the efficacy of the two most commonly prescribed opiate substitute medications in the UK--methadone hydrochloride (methadone oral solution) and Suboxone (buprenorphine-naloxone sublingual tablets)--for reducing current heroin users' (n = 34) days of heroin use, and preventing short-term abstainers (n = 37) from relapsing to regular heroin use. All patients had been prescribed either methadone or Suboxone for maintenance for 6 months prior to intake. Results showed that when controlling for a number of patient-level covariates, both methadone and Suboxone significantly reduced current users' days of heroin use between the 90 days prior to intake and at the 8-month follow-up, with Suboxone yielding a significantly larger magnitude reduction in heroin use days than methadone. Methadone and Suboxone were highly and equally effective for preventing relapse to regular heroin use, with all but 3 of 37 (91.9%) patients who were abstinent at intake reporting past 90-day point prevalence heroin abstinence at the 8-month follow-up. Overall, prescribing methadone or Suboxone for eight continuous months was highly effective for initiating abstinence from heroin use, and for converting short-term abstinence to long-term abstinence. However, the study design, which was based on a relatively small sample size and was not able randomise patients to medication and so could not control for the effects of potential prognostic factors inherent within each patient group, means that these conclusions can only be made tentatively. These positive but preliminary indications of the

  5. Managing Substitute Teaching.

    ERIC Educational Resources Information Center

    Jones, Kevin R.

    1999-01-01

    This news brief presents information on managing substitute teaching. The information is based on issues discussed at a summit meeting which included public school administrators and personnel directors from around the nation. The main topics of concern focused around four core components related to the management of substitute teaching:…

  6. Population pharmacokinetics, brain distribution, and pharmacodynamics of 2nd generation dopamine transporter selective benztropine analogs developed as potential substitute therapeutics for treatment of cocaine abuse.

    PubMed

    Syed, Shariq A; Newman, Amy H; Othman, Ahmed A; Eddington, Natalie D

    2008-05-01

    A second generation of N-substituted 3alpha-[bis(4'-fluorophenyl)methoxy]-tropanes (GA 1-69, JHW 005 and JHW 013) binds with high affinity to the dopamine transporter (DAT) and are highly selective toward DAT compared to muscarinic receptor binding (M1). The objective of this study was to characterize brain distribution, pharmacokinetics, and pharmacodynamics [extracellular brain dopamine (DA) levels] of three novel N-substituted benztropine (BZT) analogs in male Sprague-Dawley rats. The BZT analogs displayed a higher distribution (Vd = 8.69-34.3 vs. 0.9 L/kg) along with longer elimination (t l/2: 4.1-5.4 vs. 0.5 h) than previously reported for cocaine. Brain-to-plasma partition coefficients were 1.3-2.5 vs. 2.1 for cocaine. The effect of the BZT analogs on extracellular brain (DA) levels ranged from minimal effects (GA 1-69) to several fold elevation (approximately 850% of basal DA for JHW 013) at the highest dose evaluated. PK/PD analysis of exposure-response data resulted in lower IC50 values for the BZT analogs compared to cocaine indicating their higher potency to inhibit DA reuptake (0.1-0.3 vs. 0.7 mg/L). These BZT analogs possess significantly different PK and PD profiles as compared to cocaine suggesting that further evaluation as cocaine abuse therapeutics is warranted.

  7. [Substitution therapy tested against amphetamine dependence].

    PubMed

    Bloniecki Kallio, Victor; Guterstam, Joar; Franck, Johan

    2016-01-01

    Amphetamine dependence is relatively common in Sweden and it is the most frequently used substance among patients with intravenous drug abuse. Current treatment options are limited but recently substitution therapy with psychostimulant medication has been evaluated in several clinical trials. Such treatment is controversial in Sweden, perhaps due to the failure of experimental prescription of psychostimulants in the 1960s. Recent clinical trials however indicate that structured treatment programs with psychostimulants might have positive effects, although the results are inconsistent and the evidence base is still limited. Future research is needed in order to determine the potential role of substitution therapy for amphetamine dependence in clinical practice. PMID:26756343

  8. Fabrication of an ultrasensitive impedimetric buprenorphine hydrochloride biosensor from computational and experimental angles.

    PubMed

    Gholivand, Mohammad-Bagher; Jalalvand, Ali R; Goicoechea, Hector C; Skov, Thomas

    2014-06-01

    For the first time, an ultrasensitive impedimetric buprenorphine hydrochloride (BN) biosensor based on immobilization of bovine serum albumin (BSA) onto multi-walled carbon nanotubes (MWCNTs)/glassy carbon electrode (BSA/MWCNTs/GCE) has been developed using initial characterization by computational methods and complementing them by experimental observations. Computational results showed that the BSA hydrophobically binds to MWCNTs which is energetically favorable and leads to spontaneous formation of the stable BSA/MWCNTs nanobiocomposite (bioconjugate). Computational results also showed that the interaction of BN with BSA is mainly driven by hydrophobic interactions. The interactions of BSA with MWCNTs and BN with BSA were also monitored by fluorescence and UV-vis spectroscopic techniques, and their results were consistent with the computational results. Morphology and electrochemical properties of the fabricated composite electrodes were examined by scanning electron microscopy (SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). Besides complementing the computational studies, experimental results showed that the addition of MWCNTs to the surface of the GCE greatly facilitated the electron transfer reactions, and also showed that the presence of BSA inhibits the interfacial electron transfer in some extent due to the non-conductive properties of BSA. On the other hand, the presence of BN may form an electroactive complex with BSA which accelerates the interfacial electron transfer and leads to obvious Faradaic impedance changes. The Faradaic impedance responses were linearly related to BN concentration between 5.0 nM and 72.0 nM and a limit of detection (LOD, 3S(b)/b) of 1.5 nM was achieved. Finally, the proposed biosensor was successfully applied to determination of BN in urine samples of both healthy and addict volunteers. The results were satisfactory and comparable to those obtained by applying the reference method based on high

  9. Gender and strain contributions to the variability of buprenorphine-related respiratory toxicity in mice.

    PubMed

    Alhaddad, Hisham; Cisternino, Salvatore; Saubamea, Bruno; Schlatter, Joel; Chiadmi, Fouad; Risède, Patricia; Smirnova, Maria; Cochois-Guégan, Véronique; Tournier, Nicolas; Baud, Frédéric J; Mégarbane, Bruno

    2013-03-01

    While most deaths from asphyxia related to buprenorphine (BUP) overdose have been reported in males, higher plasma concentrations of BUP and its toxic metabolite norbuprenorphine (NBUP) have been observed in females. We previously demonstrated that P-glycoprotein (P-gp) modulation at the blood-brain barrier (BBB) contributes highly to BUP-related respiratory toxicity, by limiting NBUP entrance into the brain. In this work, we sought to investigate the role of P-gp-mediated transport at the BBB in gender and strain-related variability of BUP and NBUP-induced respiratory effects in mice. Ventilation was studied using plethysmography, P-gp expression using western blot, and transport at the BBB using in situ cerebral perfusion. In male Fvb and Swiss mice, BUP was responsible for ceiling respiratory effects. NBUP-related reduction in minute volume was dose-dependent but more marked in Fvb (p<0.01 at 1mg/kg NBUP and p<0.001 at 3 and 9mg/kg NBUP) than in Swiss mice (p<0.001 at 9mg/kg NBUP). Female Fvb mice were more susceptible to BUP than males with significantly increased inspiratory time (p<0.05) and to NBUP with significantly increased expiratory time (p<0.01). Following BUP administration, plasma BUP concentrations were significantly higher (p<0.01) and plasma NBUP concentrations significantly lower (p<0.001) in Fvb mice compared to Swiss mice. Plasma BUP concentrations were significantly higher (p<0.05) and plasma NBUP concentrations significantly lower (p<0.01) in male compared to female Fvb mice. In contrast, following NBUP administration, comparable plasma NBUP concentrations were observed in both genders and strains. No differences in P-gp expression or BUP and NBUP transport across the BBB were observed between male and female Fvb mice as well as between Swiss and Fvb mice. Our results suggest that P-gp-mediated transport across the BBB does not play a key-role in gender and strain-related variability in BUP and NBUP-induced respiratory toxicity in mice. Both

  10. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  11. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  12. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  13. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  14. 40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject...

  15. Synthesis of substituted pyrazines

    DOEpatents

    Pagoria, Philip F.; Zhang, Mao Xi

    2016-10-04

    A method for synthesizing a pyrazine-containing material according to one embodiment includes contacting an iminodiacetonitrile derivative with a base and a reagent selected from a group consisting of hydroxylamine, a hydroxylamine salt, an aliphatic primary amine, a secondary amine, an aryl-substituted alkylamine a heteroaryl-substituted alkyl amine, an alcohol, an alkanolamine and an aryl alcoholamine. Additional methods and several reaction products are presented. ##STR00001##

  16. Simultaneous determination of opiates, methadone, buprenorphine and metabolites in human urine by superficially porous liquid chromatography tandem mass spectrometry.

    PubMed

    Lin, Huei-Ru; Chen, Chin-Lun; Huang, Chieh-Liang; Chen, Shao-Tsu; Lua, Ahai-Chuang

    2013-04-15

    For monitoring compliance of methadone or buprenorphine maintenance patient, a method for the simultaneous determination of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, opiates (morphine, codeine, 6-monoacetylmorphine) in urine by superficially porous liquid chromatography tandem mass spectrometry was developed and validated. After enzyme digestion and liquid-liquid extraction, reverse-phase separation was achieved in 5.2 min and quantification was performed by multiple reaction monitoring. Chromatographic separation was performed at 40 °C on a reversed phase Poroshell column with gradient elution. The mobile phase consisted of water and methanol, each containing 0.1% formic acid, at a flow rate of 0.32 mL/min. Intra-day and inter-day precision were less than 12.1% and accuracy was between -9.8% and 13.7%. Extraction efficiencies were more than 68%. Although ion suppression was detected, deuterated internal standards compensated for these effects. Carryover was minimal, less than 0.20%. All analytes were stable at room temperature for 16 h, 4 °C for 72 h, and after three freeze-thaw cycles. The assay also fulfilled compound identification criteria in accordance with the European Commission Decision 2002/657/EC. We analyzed 62 urine samples from patients received maintenance therapy and found that 54.8% of the patient samples tested were detected for morphine, codeine, or 6-monoacetylmorphine. This method provides a reliable and simultaneous quantification of opiates, maintenance drugs, and their metabolites in urine samples. It facilitates the routine monitoring in individuals prescribed the drug to ensure compliance and help therapeutic process. PMID:23507455

  17. Effect of oral OPC-28326, a selective femoral arterial vasodilator, on hindlimb subcutaneous tissue temperature in conscious dogs under buprenorphine sedation.

    PubMed

    Orito, Kensuke; Imaizumi, Takashi; Yoshida, Kenji; Kishi, Masami; Fujiki, Hiroyuki; Mori, Toyoki

    2002-01-01

    In dogs, rectal temperature was decreased to about 36 degrees C at 2 to 2.5 h after sedation with buprenorphine (0.3 mg/body, i.m.), and hindlimb subcutaneous tissue temperature (T(SC)) in the thigh decreased in a similar manner. T(SC) in the dorsum of the foot showed a greater decrease than that in the thigh. OPC-28326 (4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate) at doses of 0.3, 1.0 and 3.0 mg/kg, p.o. inhibited the buprenorphine-induced decrease in T(SC) in the dorsum dose-dependently, but had little effect on that in the thigh or rectal temperature. In conclusion, T(SC) in the extremities were more sensitive to core temperature and peripheral circulation.

  18. Opioid use in Albuquerque, New Mexico: a needs assessment of recent changes and treatment availability

    PubMed Central

    2014-01-01

    Background New Mexico has consistently high rates of drug-induced deaths, and opioid-related treatment admissions have been increasing over the last two decades. Youth in New Mexico are at particular risk: they report higher rates of nonmedical prescription opioid use than those over age 25, are more likely than their national counterparts to have tried heroin, and represent an increasing proportion of heroin overdoses. Methods Commissioned by the City of Albuquerque, semistructured interviews were conducted from April to June of 2011 with 24 substance use treatment agencies and eight key stakeholders in Albuquerque to identify recent changes in the treatment-seeking population and gaps in treatment availability. Themes were derived using template analysis and data were analyzed using NVivo 9 software. Results Respondents reported a noticeable increase in youth seeking treatment for opioid use and a general increase in nonmedical prescription opioid use. Most noted difficulties with finding buprenorphine providers and a lack of youth services. Additionally, stigma, limited interagency communication and referral, barriers to prescribing buprenorphine, and a lack of funding were noted as preventing opioid users from quickly accessing effective treatment. Conclusions Recommendations for addressing these issues include developing youth-specific treatment programs, raising awareness about opioid use among youth, increasing the availability of buprenorphine through provider incentives and education, developing a resource guide for individuals seeking treatment in Albuquerque, and prioritizing interagency communication and referrals. PMID:24942534

  19. Azole antifungal inhibition of buprenorphine, methadone and oxycodone in vitro metabolism.

    PubMed

    Moody, David E; Liu, Fenyun; Fang, Wenfang B

    2015-06-01

    Opioid-related mortality rates have escalated. Drug interactions may increase blood concentrations of the opioid. We therefore used human liver microsomes (HLMs) and cDNA-expressed human cytochrome P450s (rCYPs) to study in vitro inhibition of buprenorphine metabolism to norbuprenorphine (CYP3A4 and 2C8), oxycodone metabolism to noroxycodone (CYP3A4 and 2C18) and oxymorphone (CYP2D6), and methadone metabolism to R- and S-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP; CYP3A4 and 2B6). In this study, we have examined the inhibitory effect of 12 (mostly antifungal) azoles. These compounds have a wide range of solubility; to keep organic solvent ≤1%, there was an equally wide range of highest concentration tested (e.g., itraconazole 5 µM to fluconazole 1000 µM). Inhibitors were first incubated with HLMs at three concentrations with or without preincubation of inhibitor with reducing equivalents to also screen for time-dependent inhibition (TDI). Posaconazole displayed evidence of TDI; metronidazole and albendazole had no significant effect. Azoles were next screened at the highest achievable concentration for non-CYP3A4 pathways. IC50 values (µM) were determined for most CYP3A4 pathways (ranges) and other pathways as dictated by screen results: clotrimazole (0.30 - 0.35; others >30 µM); econazole (2.2 - 4.9; 2B6 R-EDDP - 9.5, S-EDDP - 6.8; 2C8 - 6.0; 2C18 - 1.0; 2D6 - 1.2); fluconazole (7.7 - 66; 2B6 - 313, 361; 2C8 - 1240; 2C18 - 17; 2D6 - 1000); itraconazole (2.5 to >5; others >5); ketoconazole (0.032 - 0.094; 2B6 - 12, 31; 2C8 - 78; 2C18 - 0.98; 2D6 - 182); miconazole (2.3 - 7.6; 2B6 - 2.8, 2.8; 2C8 - 5.3; 2C18 - 3.1; 2D6 - 5.9); posaconazole (3.4 - 20; 2C18 - 3.8; others >30); terconazole (0.48 to >10; 2C18 - 8.1; others >10) and voriconazole (0.40 - 15; 2B6 - 2.4, 2.5; 2C8 - 170; 2C18 - 13; 2D6 >300). Modeling based on estimated Ki values and plasma concentrations from the literature suggest that the orally administered azoles, particularly

  20. The substitutability of reinforcers.

    PubMed

    Green, Leonard; Freed, Debra E

    1993-07-01

    Substitutability is a construct borrowed from microeconomics that describes a continuum of possible interactions among the reinforcers in a given situation. Highly substitutable reinforcers, which occupy one end of the continuum, are readily traded for each other due to their functional similarity. Complementary reinforcers, at the other end of the continuum, tend to be consumed jointly in fairly rigid proportion, and therefore cannot be traded for one another except to achieve that proportion. At the center of the continuum are reinforcers that are independent with respect to each other; consumption of one has no influence on consumption of another. Psychological research and analyses in terms of substitutability employ standard operant conditioning paradigms in which humans and nonhumans choose between alternative reinforcers. The range of reinforcer interactions found in these studies is more readily accommodated and predicted when behavior-analytic models of choice consider issues of substitutability. New insights are gained into such areas as eating and drinking, electrical brain stimulation, temporal separation of choice alternatives, behavior therapy, drug use, and addictions. Moreover, the generalized matching law (Baum, 1974) gains greater explanatory power and comprehensiveness when measures of substitutability are included. PMID:16812696

  1. The substitutability of reinforcers

    PubMed Central

    Green, Leonard; Freed, Debra E.

    1993-01-01

    Substitutability is a construct borrowed from microeconomics that describes a continuum of possible interactions among the reinforcers in a given situation. Highly substitutable reinforcers, which occupy one end of the continuum, are readily traded for each other due to their functional similarity. Complementary reinforcers, at the other end of the continuum, tend to be consumed jointly in fairly rigid proportion, and therefore cannot be traded for one another except to achieve that proportion. At the center of the continuum are reinforcers that are independent with respect to each other; consumption of one has no influence on consumption of another. Psychological research and analyses in terms of substitutability employ standard operant conditioning paradigms in which humans and nonhumans choose between alternative reinforcers. The range of reinforcer interactions found in these studies is more readily accommodated and predicted when behavior-analytic models of choice consider issues of substitutability. New insights are gained into such areas as eating and drinking, electrical brain stimulation, temporal separation of choice alternatives, behavior therapy, drug use, and addictions. Moreover, the generalized matching law (Baum, 1974) gains greater explanatory power and comprehensiveness when measures of substitutability are included. PMID:16812696

  2. Evaluation of bone substitutes for treatment of peri-implant bone defects: biomechanical, histological, and immunohistochemical analyses in the rabbit tibia

    PubMed Central

    2016-01-01

    Purpose We sought to evaluate the effectiveness of bone substitutes in circumferential peri-implant defects created in the rabbit tibia. Methods Thirty rabbits received 45 implants in their left and right tibia. A circumferential bone defect (6.1 mm in diameter/4 mm depth) was created in each rabbit tibia using a trephine bur. A dental implant (4.1 mm × 8.5 mm) was installed after the creation of the defect, providing a 2-mm gap. The bone defect gaps between the implant and the bone were randomly filled according to the following groups: blood clot (CO), particulate Bio-Oss® (BI), and Bio-Oss® Collagen (BC). Ten animals were euthanized after periods of 15, 30, and 60 days. Biomechanical analysis by means of the removal torque of the implants, as well as histologic and immunohistochemical analyses for protein expression of osteocalcin (OC), Runx2, OPG, RANKL, and TRAP were evaluated. Results For biomechanics, BC showed a better biological response (61.00±15.28 Ncm) than CO (31.60±14.38 Ncm) at 30 days. Immunohistochemical analysis showed significantly different OC expression in CO and BC at 15 days, and also between the CO and BI groups, and between the CO and BC groups at 60 days. After 15 days, Runx2 expression was significantly different in the BI group compared to the CO and BC groups. RANKL expression was significantly different in the BI and CO groups and between the BI and BC groups at 15 days, and also between the BI and CO groups at 60 days. OPG expression was significantly higher at 60 days postoperatively in the BI group than the CO group. Conclusions Collectively, our data indicate that, compared to CO and BI, BC offered better bone healing, which was characterized by greater RUNX2, OC, and OPG immunolabeling, and required greater reversal torque for implant removal. Indeed, along with BI, BC presents promising biomechanical and biological properties supporting its possible use in osteoconductive grafts for filling peri-implant gaps. PMID:27382506

  3. Medication Assisted Treatment for Opioid Use Disorders. Final rule.

    PubMed

    2016-07-01

    This final rule increases access to medication-assisted treatment (MAT) with buprenorphine and the combination buprenorphine/naloxone (hereinafter referred to as buprenorphine) in the office-based setting as authorized under the United States Code. Section 303(g)(2) of the Controlled Substances Act (CSA) allows individual practitioners to dispense or prescribe Schedule III, IV, or V controlled substances that have been approved by the Food and Drug Administration (FDA). Section 303(g)(2)(B)(iii) of the CSA allows qualified practitioners who file an initial notification of intent (NOI) to treat a maximum of 30 patients at a time. After 1 year, the practitioner may file a second NOI indicating his/her intent to treat up to 100 patients at a time. This final rule will expand access to MAT by allowing eligible practitioners to request approval to treat up to 275 patients under section 303(g)(2) of the CSA. The final rule also includes requirements to ensure that patients receive the full array of services that comprise evidence-based MAT and minimize the risk that the medications provided for treatment are misused or diverted. PMID:27400463

  4. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato...

  5. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato...

  6. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato...

  7. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato...

  8. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato...

  9. The Age of Substitutability

    ERIC Educational Resources Information Center

    Goeller, H. E.; Weinberg, Alvin M.

    1976-01-01

    Dwindling mineral resources might cause a shift from nonrenewable resources to renewable resources and inexhaustible elements such as iron and aluminum. Alternative energy sources such as breeder, fusion, solar, and geothermal power must be developed for production and recycling of materials. Substitution and, hence, living standards ultimately…

  10. Performing Substitute Teaching

    ERIC Educational Resources Information Center

    Bletzer, Keith V.

    2010-01-01

    Formal education is both a right and an obligation bestowed on young people in most all nations of the world. Teachers (adults) and students (youth) form a co-present dyadic contract that must be maintained within the classroom. Substitute teachers fill a role in sustaining the integrity of this teacher-student link, whenever teachers are absent.…

  11. Screening Substitute Teachers.

    ERIC Educational Resources Information Center

    Kakkuri, Mark

    2000-01-01

    The screening process a school district uses in hiring substitute teachers is critical to striking a balance between required qualifications and immediate need. Typically, screening involves at least one of the following: pre-screening, paper and pencil screening, interviews, and background checks, each of which is used to different degrees…

  12. [Innovative wound therapy and skin substitutes for burns].

    PubMed

    Vogt, P M; Kolokythas, P; Niederbichler, A; Knobloch, K; Reimers, K; Choi, C Y

    2007-04-01

    The success of modern burn therapy is based mainly on special burn intensive care, topical treatment, early eschar excision, and wound closure by immediate skin grafting or skin substitutes. This paper describes the current state of wound care and skin substitutes in burn therapy.

  13. Evaluation of buprenorphine LUCIO immunoassay versus GC-MS using urines from a workplace drug testing program.

    PubMed

    Alves, Marcela Nogueira Rabelo; Piccinotti, Alberto; Tameni, Silvia; Polettini, Aldo

    2013-04-01

    The buprenorphine (BUP) LUCIO Nal Von Minden screening assay was evaluated. Urine samples from subjects enrolled in a workplace drug testing program were screened according to the manufacturer's instruction using a Roche COBAS Integra 800 analyser. For gas chromatography-mass spectrometry (GC-MS) confirmatory analysis, samples were submitted to enzymatic hydrolysis with β-glucuronidase and mixed-mode solid-phase extraction. Imprecision (coefficient of variation) for 3.0, 7.0, and 13.0 ng/mL calibrators varied within 2.8-8.7 intra-day (n = 20) and 7.7-8.6 inter-day (n = 19). Inaccuracy (bias) was between -5.6-30.5 intra-day and -13.2-4.2 inter-day. At the 5 ng/mL cut-off, the immunoassay showed 100% sensitivity and 88% specificity, with an overall agreement of 94% between immunoassay and GC-MS. Raising the cut-off to 10 ng/mL provided an identical overall agreement between immunoassay and GC-MS (94%), despite the decrease in sensitivity (90%) and the increase in specificity (100%). According to these results, the BUP LUCIO Nal Von Minden screening assay provides adequate sensitivity and specificity for BUP screening in urine samples using a cut-off concentration of 5 ng/mL.

  14. Endovascular Treatment of Infected Brachial Pseudoaneurysm in an Intravenous Drug Abuser: A Case Report.

    PubMed

    Boieru, Raluca; Georg, Yannick; Ramlugun, Dharmesh; Martinot, Martin; Camin, Amelie; Matysiak, Lucien; Kretz, Benjamin

    2015-10-01

    We report the case of a 36-year-old male, admitted in the emergency room with a nonruptured brachial pseudoaneurysm after buprenorphine injection, with no signs of distal acute ischemia. After endovascular treatment with a nitinol covered stent associated with adapted antibiotherapy and 35 days of hospitalizations, the patient was discharged with good short results but stent need to be removed at 6 months for thrombosis and partial exposure through the wound. PMID:26142880

  15. A behavioral intervention for improving verbal behaviors of heroin addicts in a treatment clinic.

    PubMed Central

    Petry, N M; Bickel, W K; Tzanis, E; Taylor, R; Kubik, E; Foster, M; Hughes, M E

    1998-01-01

    Positively reinforcing appropriate behaviors improved verbal behaviors of opioid-dependent patients in a buprenorphine treatment clinic. During B phases of an ABAB design, clients received stickers for engaging in appropriate verbal or nonverbal behaviors. Each sticker provided a chance of winning $25. No reinforcement was provided during the A phases. Appropriate verbal behaviors increased during reinforcement periods, and inappropriate verbal behaviors decreased. PMID:9652105

  16. Economic aspects of drug substitution

    PubMed Central

    Salehi, Hossein; Schweitzer, Stuart O.

    1985-01-01

    One of the major directions of health policy is the attempt to contain expenditures on pharmaceuticals by encouraging substitution of generic for brand name drug products. Yet, a major marketing survey of prescribing and dispensing patterns in California in 1977 found relatively little drug substitution occurring, and in fact substitution of more expensive products occurred more frequently than did substitution of less expensive products. This article tests alternative models of pharmacy dispensing behavior to better explain substitution patterns and it estimates price functions to measure the extent to which cost savings on generic products are passed on to consumers. PMID:10311162

  17. 40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic). 721.10214 Section 721.10214... Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle (generic... identified generically as poly(oxyalkylenediyl),.alpha.-substituted...

  18. SUBSTITUTION REACTIONS FOR THE DETOXIFICATION OF HAZARDOUS CHEMICALS

    EPA Science Inventory

    Chemical Treatment is one of several treatment techniques used for the remediation of toxic and hazardous chemicals. Chemical treatment in this report is defined as substitution of halogens by hydrogens for the conversion of halogenated organic toxicant into its native hydrocarb...

  19. Presence of illicit drugs and metabolites in influents and effluents of 25 sewage water treatment plants and map of drug consumption in France.

    PubMed

    Nefau, Thomas; Karolak, Sara; Castillo, Luis; Boireau, Véronique; Levi, Yves

    2013-09-01

    Consumption of illicit drugs is a new concern for water management that must be considered not only because of the social and public health aspects but also in an environmental context in relation with the contamination of surface waters. Indeed, sewage treatment plant (STP) effluents contain drug residues that have not been eliminated since STP treatments are not completely efficient in their removal. We developed and validated an HPLC-MS/MS analytical method to assess the concentrations of 17 illicit drugs and metabolites in raw urban wastewaters: cocaine and its metabolites, amphetamine and amphetamine-likes (methamphetamine, MDMA, MDEA, MDA), opiates and opiate substitutes (methadone and buprenorphine), and THC-COOH cannabis metabolite. This method has been applied to the analysis of influent and effluent samples from 25 STPs located in France all over the country. The results allowed evaluating the drug consumption in the areas connected to the STPs and the efficiency of the treatment technology implied. We selected STPs according to their volume capacity, their treatment technologies (biofilters, activated sludges, MBR) and their geographical location. In influents, the concentrations varied between 6 ng/L for EDDP (main metabolite of methadone) and 3050 ng/L for benzoylecgonine (cocaine metabolite). Consumption maps were drawn for cocaine, MDMA, opiates, cannabis and amphetamine-like compounds. Geographical significant differences were observed and highlighted the fact that drug consumption inside a country is not homogeneous. In parallel, comparisons between STP technology processes showed differences of efficiency. More, some compounds appear very resistant to STP processes leading to the contamination of receiving water. PMID:23770552

  20. Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry.

    PubMed

    Concheiro, Marta; Shakleya, Diaa M; Huestis, Marilyn A

    2011-04-01

    A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3'-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1-1,000 ng/patch, except EME 5-1,000 ng/patch. Intra-, inter-day and total imprecision were <10.1%CV, analytical recovery 87.2-107.7%, extraction efficiency 35.3-160.9%, and process efficiency 25.5-91.7%. Ion suppression was detected for EME (-63.3%) and EDDP (-60.4%), and enhancement for NBUP (42.6%). Deuterated internal standards compensated for these effects. No carryover was detected, and all analytes were stable for 24 h at 22 °C, 72 h at 4 °C, and after three freeze/thaw cycles. The method was applied to weekly sweat patches from an opioid-dependent BUP-maintained pregnant woman; 75.0% of sweat patches were positive for BUP, 93.8% for cocaine, 37.5% for opiates, 6.3% for methadone and all for tobacco biomarkers. This method permits a fast and simultaneous quantification of 14 drugs and metabolites in sweat patches, with good selectivity and sensitivity. PMID:21125263

  1. Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry

    PubMed Central

    Concheiro, Marta; Shakleya, Diaa M.

    2013-01-01

    A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3′-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1–1,000 ng/patch, except EME 5–1,000 ng/patch. Intra-, inter-day and total imprecision were <10.1%CV, analytical recovery 87.2–107.7%, extraction efficiency 35.3– 160.9%, and process efficiency 25.5–91.7%. Ion suppression was detected for EME (−63.3%) and EDDP (−60.4%), and enhancement for NBUP (42.6%). Deuterated internal standards compensated for these effects. No carryover was detected, and all analytes were stable for 24 h at 22 °C, 72 h at 4 °C, and after three freeze/thaw cycles. The method was applied to weekly sweat patches from an opioid-dependent BUP-maintained pregnant woman; 75.0% of sweat patches were positive for BUP, 93.8% for cocaine, 37.5% for opiates, 6.3% for methadone and all for tobacco biomarkers. This method permits a fast and simultaneous quantification of 14 drugs and metabolites in sweat patches, with good selectivity and sensitivity. PMID:21125263

  2. Explicit Substitutions and All That

    NASA Technical Reports Server (NTRS)

    Ayala-Rincon, Mauricio; Munoz, Cesar; Busnell, Dennis M. (Technical Monitor)

    2000-01-01

    Explicit substitution calculi are extensions of the Lambda-calculus where the substitution mechanism is internalized into the theory. This feature makes them suitable for implementation and theoretical study of logic-based tools such as strongly typed programming languages and proof assistant systems. In this paper we explore new developments on two of the most successful styles of explicit substitution calculi: the lambda(sigma)- and lambda(s(e))-calculi.

  3. Explicit Substitutions and All That

    NASA Technical Reports Server (NTRS)

    Ayala-Rincon, Mauricio; Munoz, Cesar

    2000-01-01

    Explicit substitution calculi are extensions of the lambda-calculus where the substitution mechanism is internalized into the theory. This feature makes them suitable for implementation and theoretical study of logic-based tools such as strongly typed programming languages and proof assistant systems. In this paper we explore new developments on two of the most successful styles of explicit substitution calculi: the lambda sigma- and lambda S(e)-calculi.

  4. Engagement and Substance Dependence in a Primary Care-Based Addiction Treatment Program for People Infected with HIV and People at High-Risk for HIV Infection.

    PubMed

    Walley, Alexander Y; Palmisano, Joseph; Sorensen-Alawad, Amy; Chaisson, Christine; Raj, Anita; Samet, Jeffrey H; Drainoni, Mari-Lynn

    2015-12-01

    To improve outcomes for people with substance dependence and HIV infection or at risk for HIV infection, patients were enrolled in a primary care-based addiction treatment program from 2008-2012 that included a comprehensive substance use assessment, individual and group counseling, addiction pharmacotherapy and case management. We examined whether predisposing characteristics (depression, housing status, polysubstance use) and an enabling resource (buprenorphine treatment) were associated with engagement in the program and persistent substance dependence at 6 months. At program enrollment 61% were HIV-infected, 53% reported heroin use, 46% reported alcohol use, 37% reported cocaine use, and 28% reported marijuana use in the past 30 days, 72% reported depression, 19% were homeless, and 53% had polysubstance use. Within 6-months 60% had been treated with buprenorphine. Engagement (defined as 2 visits in first 14 days and 2 additional visits in next 30 days) occurred in 64%; 49% had substance dependence at 6-months. Receipt of buprenorphine treatment was associated with engagement (Adjusted Odds Ratio (AOR) 8.32 95% CI: 4.13-16.77). Self-reported depression at baseline was associated with substance dependence at 6-months (AOR 3.30 95% CI: 1.65-6.61). Neither housing status nor polysubstance use was associated with engagement or substance dependence. The FAST PATH program successfully engaged and treated patients in a primary care-based addiction treatment program. Buprenorphine, a partial opioid agonist, was a major driver of addiction treatment engagement. Given depression's association with adverse outcomes in this clinical population, including mental health treatment as part of integrated care holds potential to improve addiction treatment outcomes. PMID:26298399

  5. Blockade of Toll-Like Receptors (TLR2, TLR4) Attenuates Pain and Potentiates Buprenorphine Analgesia in a Rat Neuropathic Pain Model

    PubMed Central

    Jurga, Agnieszka M.; Rojewska, Ewelina; Makuch, Wioletta; Pilat, Dominika; Przewlocka, Barbara

    2016-01-01

    Accumulating evidence indicates that microglial TLR2 and TLR4 play a significant role in nociception. Experiments were conducted to evaluate the contribution of TLR2 and TLR4 and their adaptor molecules to neuropathy and their ability to amplify opioid effectiveness. Behavioral tests (von Frey's and cold plate) and biochemical (Western blot and qRT-PCR) analysis of spinal cord and DRG tissue were conducted after chronic constriction injury (CCI) to the sciatic nerve. Repeated intrathecal administration of LPS-RS (TLR2 and TLR4 antagonist) and LPS-RS Ultrapure (TLR4 antagonist) attenuated allodynia and hyperalgesia. Biochemical analysis revealed time-dependent upregulation of mRNA and/or protein levels of TLR2 and TLR4 and MyD88 and TRIF adaptor molecules, which was paralleled by an increase in IBA-1/CD40-positive cells under neuropathy. LPS-RS and LPS-RS Ultrapure similarly influenced opioid analgesia by enhancing the effectiveness of buprenorphine but not morphine. Summing up, in light of their upregulation over the course of pain, both TLR2 and TLR4 may indeed play a significant role in neuropathy, which could be linked to the observed activation of IBA-1/CD40-positive cells. Blockade of TLR2 and TLR4 produced analgesia and enhanced buprenorphine's effectiveness, which suggests that they may be a putative target for future pharmacological pain relief tools, especially for opioid rotation, when the effect of morphine is tolerated. PMID:26962463

  6. [Substitution in psychogeriatrics. A comparative study in nursing homes and substitution projects in Drenthe].

    PubMed

    Schreurs, M

    1995-02-01

    Due to a strong increase of the ageing population in the Netherlands there is a growing need for care for psychogeriatric patients. The shortage of beds in psychogeriatric nursing homes has led to the development of substitute care in residential homes for the elderly and in community centers. If substitution is realized in these substitute care projects in the sense that alternative services are delivered for patients who would otherwise have been admitted to nursing homes, the level of impairment and disruptive behaviour should be of the same level in nursing homes and substitute care projects. Groups of patients of three nursing homes, three day-treatment facilities, eight day-care-projects in residential homes for the elderly and seven centers for day-care in the community were compared. Sociodemographic characteristics, behaviour and care-patterns of all 670 patients who were in care on the first of October of 1992 in these services were investigated. An assessment-scale for elderly patients, based on the Stockton Geriatric Rating Scale, was used to investigate behaviour. Substitute care appears to be possible for a limited and specific group of patients. Substitution for the severely disturbed patients (over 40% of the nursing home patients) does not seem to be possible. Due to the development of substitute care for psychogeriatric patients in residential homes for the elderly and centers for day-care in the community, services seem to develop towards more specific and specialized care. We recommend the foundation of a psychogeriatric case register, which allows the study of the transfer of patients across facilities.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Geographic variability in HIV and injection drug use in Ukraine: Implications for integration and expansion of drug treatment and HIV care

    PubMed Central

    Zaller, Nickolas; Mazhnaya, Alonya; Larney, Sarah; Islam, Zahed; Shost, Alyona; Prokhorova, Tatiana; Rybak, Natasha; Flanigan, Timothy

    2015-01-01

    Background Ukraine has the highest HIV burden of any European country with much of the current HIV epidemic concentrated among people who inject drugs (PWIDs) and their sexual partners. Opiate substitution therapy (OST) is limited in Ukraine and expansion of OST is urgently needed to help stem the tide of the HIV epidemic. Methods We accessed publicly available data in Ukraine in order to explore geographic variability with respect to prevalence of HIV, PWIDs and OST programmes. Results The regions of Ukraine with the largest number of opioid dependent persons (the south and eastern portions of the country) correspond to the regions with the highest HIV prevalence and HIV incidence. The number of opioid PWIDs per 100,000 population as well as the number of all OST treatment slots per 100,000 varied significantly across the three HIV prevalence categories. Overall, the proportion of individuals receiving either methadone maintenance therapy (MMT) or buprenorphine maintenance therapy (BMT) was quite low: average across categories: 7.3% and 0.4%, respectively. Additionally, less than half of OST patients receiving MMT or BMT were HIV positive patients. Conclusion There is significant geographic variability in both numbers of HIV positive individuals and numbers of PWIDs across Ukraine, however, there may be a more concentrated epidemic among PWIDs in many regions of the country. Scale up of addiction treatment for PWID, especially OST, can have a significant impact on preventing injection related morbidity, such as HIV and HCV infection. Ukraine can learn from the mistakes other nations have made in denying critical treatment opportunities to PWID. PMID:25304049

  8. Displacement, Substitution, Sublimation: A Bibliography.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, Bonnie C.

    Sigmund Freund worked with the mechanisms of displacement, substitution, and sublimation. These mechanisms have many similarities and have been studied diagnostically and therapeutically. Displacement and substitution seem to fit in well with phobias, hysterias, somatiyations, prejudices, and scapegoating. Phobias, prejudices, and scapegoating…

  9. How Do Substitute Teachers Substitute? An Empirical Study of Substitute-Teacher Labor Supply

    ERIC Educational Resources Information Center

    Gershenson, Seth

    2012-01-01

    This paper examines the daily labor supply of a potentially important, but often overlooked, source of instruction in U.S. public schools: substitute teachers. I estimate a sequential binary-choice model of substitute teachers' job-offer acceptance decisions using data on job offers made by a randomized automated calling system. Importantly, this…

  10. An intronic variant in OPRD1 predicts treatment outcome for opioid dependence in African-Americans.

    PubMed

    Crist, Richard C; Clarke, Toni-Kim; 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

    2013-09-01

    Although buprenorphine and methadone are both effective treatments for opioid dependence, their efficacy can vary significantly among patients. Genetic differences may explain some of the variability in treatment outcome. Understanding the interactions between genetic background and pharmacotherapy may result in more informed treatment decisions. This study is a pharmacogenetic analysis of the effects of genetic variants in OPRD1, the gene encoding the δ-opioid receptor, on the prevalence of opioid-positive urine tests in African-Americans (n=77) or European-Americans (n=566) undergoing treatment for opioid dependence. Patients were randomly assigned to treatment with either methadone or buprenorphine/naloxone (Suboxone) over a 24-week open-label clinical trial, in which illicit opioid use was measured by weekly urinalysis. In African-Americans, the intronic SNP rs678849 predicted treatment outcome for both medications. Methadone patients with the CC genotype were less likely to have opioid-positive urine tests than those in the combined CT and TT genotypes group (relative risk (RR)=0.52, 95% confidence interval (CI)=0.44-0.60, p=0.001). In the buprenorphine treatment group, however, individuals with the CC genotype were more likely to have positive opioid drug screens than individuals in the combined CT and TT genotypes group (RR=2.17, 95% CI=1.95-2.68, p=0.008). These findings indicate that the genotype at rs678849 predicts African-American patient response to two common treatments for opioid dependence, suggesting that matching patients to treatment type based on the genotype at this locus may improve overall treatment efficacy. This observation requires confirmation in an independent population. PMID:23612435

  11. An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans

    PubMed Central

    Crist, Richard C; Clarke, Toni-Kim; 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

    Although buprenorphine and methadone are both effective treatments for opioid dependence, their efficacy can vary significantly among patients. Genetic differences may explain some of the variability in treatment outcome. Understanding the interactions between genetic background and pharmacotherapy may result in more informed treatment decisions. This study is a pharmacogenetic analysis of the effects of genetic variants in OPRD1, the gene encoding the δ-opioid receptor, on the prevalence of opioid-positive urine tests in African-Americans (n=77) or European-Americans (n=566) undergoing treatment for opioid dependence. Patients were randomly assigned to treatment with either methadone or buprenorphine/naloxone (Suboxone) over a 24-week open-label clinical trial, in which illicit opioid use was measured by weekly urinalysis. In African-Americans, the intronic SNP rs678849 predicted treatment outcome for both medications. Methadone patients with the CC genotype were less likely to have opioid-positive urine tests than those in the combined CT and TT genotypes group (relative risk (RR)=0.52, 95% confidence interval (CI)=0.44–0.60, p=0.001). In the buprenorphine treatment group, however, individuals with the CC genotype were more likely to have positive opioid drug screens than individuals in the combined CT and TT genotypes group (RR=2.17, 95% CI=1.95–2.68, p=0.008). These findings indicate that the genotype at rs678849 predicts African-American patient response to two common treatments for opioid dependence, suggesting that matching patients to treatment type based on the genotype at this locus may improve overall treatment efficacy. This observation requires confirmation in an independent population. PMID:23612435

  12. Buprenorphine and norbuprenorphine quantification in human plasma by simple protein precipitation and ultra-high performance liquid chromatography tandem mass spectrometry.

    PubMed

    Lüthi, Guillaume; Blangy, Valeria; Eap, Chin B; Ansermot, Nicolas

    2013-04-15

    A highly sensitive ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed for the quantification of buprenorphine and its major metabolite norbuprenorphine in human plasma. In order to speed up the process and decrease costs, sample preparation was performed by simple protein precipitation with acetonitrile. To the best of our knowledge, this is the first application of this extraction technique for the quantification of buprenorphine in plasma. Matrix effects were strongly reduced and selectivity increased by using an efficient chromatographic separation on a sub-2 μm column (Acquity UPLC BEH C18 1.7 μm, 2.1×50 mm) in 5 min with a gradient of ammonium formate 20 mM pH 3.05 and acetonitrile as mobile phase at a flow rate of 0.4 ml/min. Detection was made using a tandem quadrupole mass spectrometer operating in positive electrospray ionization mode, using multiple reaction monitoring. The procedure was fully validated according to the latest Food and Drug Administration guidelines and the Société Française des Sciences et Techniques Pharmaceutiques. Very good results were obtained by using a stable isotope-labeled internal standard for each analyte, to compensate for the variability due to the extraction and ionization steps. The method was very sensitive with lower limits of quantification of 0.1 ng/ml for buprenorphine and 0.25 ng/ml for norbuprenorphine. The upper limit of quantification was 250 ng/ml for both drugs. Trueness (98.4-113.7%), repeatability (1.9-7.7%), intermediate precision (2.6-7.9%) and internal standard-normalized matrix effects (94-101%) were in accordance with international recommendations. The procedure was successfully used to quantify plasma samples from patients included in a clinical pharmacogenetic study and can be transferred for routine therapeutic drug monitoring in clinical laboratories without further development. PMID:23357637

  13. Vitreous substitutes: challenges and directions

    PubMed Central

    Gao, Qian-Ying; Fu, Yue; Hui, Yan-Nian

    2015-01-01

    The natural vitreous body has a fine structure and complex functions. The imitation of the natural vitreous body by vitreous substitutes is a challenging work for both researchers and ophthalmologists. Gases, silicone oil, heavy silicone oil and hydrogels, particularly the former two vitreous substitutes are clinically widely used with certain complications. Those, however, are not real artificial vitreous due to lack of structure and function like the natural vitreous body. This article reviews the situations, challenges, and future directions in the development of vitreous substitutes, particularly the experimental and clinical use of a new artificial foldable capsular vitreous body. PMID:26085987

  14. Substitution Rates under Stabilizing Selection

    PubMed Central

    Hastings, Alan

    1987-01-01

    Allelic substitutions under stabilizing phenotypic selection on quantitative traits are studied in Monte Carlo simulations of 8 and 16 loci. The results are compared and contrasted to analytical models based on work of M. Kimura for two and "infinite" loci. Selection strengths of S = 4Nes approximately four (which correspond to reasonable strengths of selection for quantitative characters) can retard substitution rates tenfold relative to rates under neutrality. An important finding is a strong dependence of per locus substitution rates on the number of loci. PMID:3609727

  15. Factor substitution in nursing homes.

    PubMed

    Cawley, John; Grabowski, David C; Hirth, Richard A

    2006-03-01

    This paper studies factor substitution in one important sector: the nursing home industry. Specifically, we measure the extent to which nursing homes substitute materials for labor when labor becomes relatively more expensive. From a policy perspective, factor substitution in this market is important because materials-intensive methods of care are associated with greater risks of morbidity and mortality among nursing home residents. Studying longitudinal data from 1991 to 2000 on nearly every nursing home in the United States, we use the method of instrumental variables (IV) to address measurement error in nursing home wages. The results from the IV models yield evidence of factor substitution: higher nursing home wages are associated with greater use of psychoactive drugs and lower quality.

  16. DESIGNING ENVIRONMENTALLY BENIGN SOLVENT SUBSTITUTES

    EPA Science Inventory

    Since the signing of 1987 Montreal Protocol, reducing and eliminating the use of harmful solvents has become an internationally imminent environmental protection mission. Solvent substitution is an effective way to achieve this goal. The Program for Assisting the Replacement of...

  17. Nucleophilic Substitution by Benzodithioate Anions.

    ERIC Educational Resources Information Center

    Bonnans-Plaisance, Chantal; Gressier, Jean-Claude

    1988-01-01

    Describes a two-session experiment designed to provide a good illustration of, and to improve student knowledge of, the Grignard reaction and nucleophilic substitution. Discusses the procedure, experimental considerations, and conclusion of this experiment. (CW)

  18. Blood substitutes based on nanobiotechnology.

    PubMed

    Chang, Thomas Ming Swi

    2006-08-01

    Stimulated by concerns of potential infective agents in donated blood, commercial enterprises have attempted to develop blood substitutes since the 1900s. After several years of development, a few of the many leads are showing promise. In this article, nanobiotechnological approaches that are now in phase III clinical trials are reviewed, followed by a discussion of how important basic knowledge gained is being used to develop new generations of blood substitutes based on nanobiotechnology.

  19. Electrophilic Substitution Reactions of Indoles

    NASA Astrophysics Data System (ADS)

    Sundberg, Richard J.

    The topic of this chapter is electrophilic substitution of indole and its derivatives. The indole ring is highly reactive at its 3-position toward protonation, halogenation, alkylation and acylation. Electrophilic substitution can be combined with inter- or intramolecular addition at C-2. Intramolecular alkylation by iminium ions (Pictet-Spengler reaction) is particularly useful. Enantioselectivity can be achieved in many conjugate addition reactions. These reactions have been applied to synthesis of both natural products and drugs.

  20. Nonallograft osteoconductive bone graft substitutes.

    PubMed

    Bucholz, Robert W

    2002-02-01

    An estimated 500,000 to 600,000 bone grafting procedures are done annually in the United States. Approximately (1/2) of these surgeries involve spinal arthrodesis whereas 35% to 40% are used for general orthopaedic applications. Synthetic bone graft substitutes currently represent only 10% of the bone graft market, but their share is increasing as experience and confidence in their use are accrued. Despite 15 to 20 years of clinical experience with various synthetic substitutes, there have been few welldesigned, controlled clinical trials of these implants. Synthetic bone graft substitutes consist of hydroxyapatite, tricalcium phosphate, calcium sulfate, or a combination of these minerals. Their fabrication technique, crystallinity, pore dimensions, mechanical properties, and resorption rate vary. All synthetic porous substitutes share numerous advantages over autografts and allografts including their unlimited supply, easy sterilization, and storage. However, the degree to which the substitute provides an osteoconductive structural framework or matrix for new bone ingrowth differs among implants. Disadvantages of ceramic implants include brittle handling properties, variable rates of resorption, poor performance in diaphyseal defects, and potentially adverse effects on normal bone remodeling. These inherent weaknesses have refocused their primary use to bone graft extenders and carriers for pharmaceuticals. The composition, histologic features, indications, and clinical experience of several of the synthetic bone graft substitutes approved for orthopaedic use in the United States are reviewed. PMID:11937865

  1. Substitutes for leadership: test of a construct.

    PubMed

    Howell, J P; Dorfman, P W

    1981-12-01

    The study reported here examined the impact of leadership substitutes on subordinate job satisfaction and organizational commitment. Leadership substitutes, as suggested by Kerr (1977), replace or "act in the place of" a specific leader behavior. Multiple regression was used to test the validity and strength of potential substitutes. Results indicated mixed support for the substitutes construct. PMID:10253689

  2. Visual evoked potential latencies of three-year-old children prenatally exposed to buprenorphine or methadone compared with non-opioid exposed children: The results of a longitudinal study.

    PubMed

    Whitham, Justine N; Spurrier, Nicola J; Baghurst, Peter A; Weston, Paul; Sawyer, Michael G

    2015-01-01

    This study compared the latency of pattern reversal visual evoked potentials (VEP) of 36-month old children exposed to opioid pharmacotherapy in utero to that of a group of non-exposed children. Pregnant women were enrolled as part of an open-label non-randomised flexible dosing longitudinal study. Participants were 21 children whose mothers were treated with buprenorphine- (n=11) or methadone-pharmacotherapy (n=10) during pregnancy, and 15 children not exposed to opioids in pregnancy. One-way between groups analyses of variance (ANOVA) were conducted to test the statistical significance of differences between the mean latencies of the peak response to two different sized checkerboard patterns (48' and 69' of retinal arc). Standard multiple regression analyses were conducted to determine whether there was a significant relationship between group status and VEP latencies after adjusting for the effect of covariates. VEP latencies ranged from 98 to 112 milliseconds (ms) for checks of 48' arc, and from 95 to 113ms for checks of 69' arc. Latencies were comparable across groups. After adjusting for covariates children prenatally exposed to methadone or buprenorphine did not differ significantly from non-opioid exposed children in their responses to either check size. Nor were there any significant differences in VEP latencies between children prenatally exposed to methadone and children prenatally exposed to buprenorphine. Head circumference (HC) was significantly associated with P100 latencies for both check sizes. Data from this controlled, non-randomised study suggest that neither buprenorphine nor methadone appear to have any long-term effects on visual maturity assessed at 36months of age.

  3. Point substitutions in Japanese alloalbumins.

    PubMed

    Arai, K; Madison, J; Huss, K; Ishioka, N; Satoh, C; Fujita, M; Neel, J V; Sakurabayashi, I; Putnam, F W

    1989-08-01

    We have completed the structural study of five rare types of inherited albumin variants (alloalbumins) discovered in the Biochemical Genetics Study of 15,581 unrelated children in Hiroshima and Nagasaki. We have also identified the structural change in five other alloalbumin specimens detected during clinical electrophoresis of sera from Japanese living near Tokyo. Each of the five albumin variants from Nagasaki and Hiroshima has a single amino acid substitution. All of these substitutions differ, and none has been reported in non-Japanese populations. No instances of proalbumin variants or of albumin B (the most frequent alloalbumins in Caucasians) were detected in the children in Hiroshima and Nagasaki. However, one instance of a variant proalbumin and two examples of albumin B occurred in Japanese from the vicinity of Tokyo. In addition a previously unreported point substitution was found in albumin Tochigi, which is present in two unrelated persons from Tochigi prefecture. Four of the point mutations in the Japanese alloalbumins are in close proximity in a short segment of the polypeptide chain (residues 354-382) in which three additional point substitutions have been reported in diverse populations. These results, combined with earlier data, suggest that point substitutions are grouped in certain segments of the albumin molecule.

  4. Safety of nonblood plasma substitutes: less frequently discussed issues.

    PubMed

    Boldt, Joachim

    2010-06-01

    A variety of different fluids are promoted to correct hypovolaemia. Apart from the crystalloid versus colloid debate, there exists also a colloid versus colloid discussion as different protein (albumin) and nonprotein colloids (dextrans, gelatins, hydroxyethyl starch preparations) are available for this purpose. The different plasma substitutes largely differ with regard to their composition and their physicochemical properties. All currently used strategies for correcting hypovolaemia have their pros and cons. At present, there is an ongoing interest in the major problems associated with the use of plasma substitutes such as their influence on coagulation and kidney function. There are, however, also some less often addressed questions concerning the use of plasma substitutes that need to be answered. Although nonblood plasma substitutes are often administered worldwide, there is still uncertainty with regard to using them in pregnancy, effects on cross-matching and blood typing, mixing with other drugs, dose limitations, the risk of calcium-containing and potassium-containing solutions, the risk of producing itching, the influence on blood sugar level or whether warming can be done safely. Unfortunately, data to answer these very practical questions are limited or are even lacking for some plasma substitutes. To further increase safety in the treatment of the hypovolaemic patient, all possible problems must be discussed and contraindications of nonblood plasma substitutes must be clearly defined.

  5. Unified optical symbolic substitution processor

    NASA Astrophysics Data System (ADS)

    Casasent, David P.

    1990-07-01

    Symbolic substitution operations can be realized optically on a correlator. This is a very attractive and efficient architecture for symbolic substitution. It allows parallel multichannel realization with a fixed set of filters (on film or easily realized on low space bandwidth product spatial light modulators) using space and frequency-multiplexing or sequential filters. All basic logic, numeric and morphological image processing functions can be achieved by symbolic substitution. Moreover, all operations are possible on one multifunctional optical processor. Morphological operations are felt to be essential for ATR and pattern recognition preprocessing in clutter. They greatly improve the role for optics by allowing the same optical architecture to be used for low, medium and high level vision.

  6. Substitution systems and nonextensive statistics

    NASA Astrophysics Data System (ADS)

    García-Morales, V.

    2015-12-01

    Substitution systems evolve in time by generating sequences of symbols from a finite alphabet: At a certain iteration step, the existing symbols are systematically replaced by blocks of Nk symbols also within the alphabet (with Nk, a natural number, being the length of the kth block of the substitution). The dynamics of these systems leads naturally to fractals and self-similarity. By using B-calculus (García-Morales, 2012) universal maps for deterministic substitution systems both of constant and non-constant length, are formulated in 1D. It is then shown how these systems can be put in direct correspondence with Tsallis entropy. A 'Second Law of Thermodynamics' is also proved for these systems in the asymptotic limit of large words.

  7. 40 CFR 721.2577 - Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Copper complex of (substituted... Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine salt... substances identified generically as copper complex of (substituted sulfonaphthyl azo substituted...

  8. 40 CFR 721.2577 - Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Copper complex of (substituted... Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine salt... substances identified generically as copper complex of (substituted sulfonaphthyl azo substituted...

  9. Production of zinc substituted hydroxyapatite using various precipitation routes.

    PubMed

    Shepherd, David; Best, Serena M

    2013-04-01

    Substituted hydroxyapatites have been investigated for use as bone grafts and have been investigated for many years. Zinc is of interest due to its potential to reduce bone resorption and antibacterial properties. However, it has proven problematic to substitute biologically significant levels of zinc into the crystal structure through wet chemical routes, whilst retaining the high temperature phase stability required for processing. The aim of this study is to investigate two different precipitation routes used to synthesize zinc substituted hydroxyapatite and to explore the effects of ammonia used in the reactions on the levels of zinc substituted into the crystal lattice. It was found that considerable amounts of ammonia are required to maintain a pH sufficiently high for the production of stoichiometric hydroxyapatite using a reaction between calcium nitrate, zinc nitrate and ammonium phosphate. X-ray fluorescence analysis showed that a significant proportion of the zinc added did not substitute into the hydroxyapatite lattice. Fourier transform infrared spectroscopy revealed the existence of a zinc-ammonia complex that, it is proposed, inhibits zinc substitution for calcium. It was found that by reacting orthophosphoric acid with calcium nitrate and zinc nitrate, the volume of ammonia required in the reaction was reduced and higher levels of zinc substitution were achieved, with up to 0.58 wt% incorporated into the hydroxyapatite lattice. The resulting products were found to be stoichiometric hydroxyapatite and did not appear to contain any extraneous calcium phosphate phases after heat treatment up to 1100 °C. X-ray diffraction and Rietveld analysis revealed that the effect of substituting zinc into the HA lattice was to decrease the a-lattice parameter whilst increasing the c-lattice. Transmission electron microscopy also showed that the incorporation of zinc reduced both the length and width of the precipitated crystals.

  10. Substituted decision making: elder guardianship.

    PubMed

    Leatherman, Martha E; Goethe, Katherine E

    2009-11-01

    The goal of this column is to help experienced clinicians navigate the judicial system when they are confronted with requests for capacity evaluations that involve guardianship (conservatorship). The interface between the growing elderly medical population and increasing requests for substituted decision making is becoming more complex. This column will help practicing psychiatrists understand the medical, legal, and societal factors involved in adult guardianship. Such understanding is necessary in order to effectively perform guardianship evaluations and adequately inform courts, patients, and families about the psychiatric diagnoses central to substituted decision making.

  11. Buprenorphine Transdermal Patch

    MedlinePlus

    ... Posted 08/31/2016]AUDIENCE: Pharmacy, Internal Medicine, Psychiatry, Neurology, Family PracticeISSUE: FDA review has found that ... opioid and benzodiazepine labeling, and new or revised patient Medication Guides. These changes include the new Boxed ...

  12. Buprenorphine Buccal (chronic pain)

    MedlinePlus

    ... Xtandi); human immunodeficiency virus (HIV) medications such as atazanavir (Reyataz, in Evotaz), delavirdine (Rescriptor), efavirenz (Sustiva, in ... it at room temperature and away from excess heat and moisture (not in the bathroom).Dispose of ...

  13. Treatment

    MedlinePlus

    ... Prevention Treatment 2003 U.S. Outbreak African Rodent Importation Ban For Clinicians Clinical Recognition Specimen Collection Treatment Smallpox ... Examining Animals with Suspected Monkeypox African Rodent Importation Ban Resources Related Links Poxvirus Molluscum Contagiosum Orf Virus ( ...

  14. 40 CFR 721.10214 - Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega.-substituted carbomonocycle...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Poly(oxyalkylenediyl),.alpha... Poly(oxyalkylenediyl),.alpha.-substituted carbomono