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1

A Urinalysis-based Comparative Study of Treatment Adherence on Buprenorphine and Buprenorphine/Naloxone Combination Used as Opioid Substitution Therapy  

PubMed Central

Objective: The objective of the current study was to explore the difference in treatment adherence to directly supervised buprenorphine and take-home buprenorphine/ naloxone combination for opioid substitution therapy. Urinalysis findings have been used to check treatment adherence on opioid substitution therapy agent. Additionally the study aimed to explore the misuse rate of buprenorphine/naloxone combination based on urinalysis findings. Design: Cross-sectional chart review Setting: Laboratory of a tertiary care drug dependence treatment center Participants: One-year laboratory urinalysis records of a tertiary care, drug-dependence treatment center in India were analyzed. All the urine samples of subjects on opioid substitution therapy with buprenorphine or buprenorphine/naloxone combination were included in the study. Measurements: Urinalysis using thin layer chromatography for buprenorphine and naloxone. In between group difference for treatment adherence on buprenorphine and buprenorphine/ naloxone combination was done using Mantel-Haenszel test. Results: A higher proportion of samples from subjects on buprenorphine/naloxone tested positive for buprenorphine as compared to subjects on buprenorphine. Twelve (7.6%) urine samples from patients on buprenorphine/naloxone tested positive for naloxone. Conclusions: The findings of the current study suggest that buprenorphine/naloxone combination has a higher adherence rate as compared to buprenorphine when used for opioid substitution therapy.

Jain, Raka

2012-01-01

2

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

Microsoft Academic Search

BACKGROUND: Both methadone- and buprenorphine-treated opioid-dependent patients frequently show cognitive deficits in attention, working memory, and verbal memory. However, no study has compared these patient groups with each other during early opioid substitution treatment (OST). Therefore, we investigated attention, working memory, and verbal memory of opioid-dependent patients within six weeks after the introduction of OST in a naturalistic setting and

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

2007-01-01

3

Buprenorphine in the Treatment of Opiate Dependence  

Microsoft Academic Search

Compelling clinical evidence establishes that buprenorphine is similar to methadone in efficacy for opiate detoxification and maintenance but safer than methadone in an overdose situation. The Drug Abuse Treatment Act of 2000 (DATA 2000) enabled US physicians with additional training to prescribe buprenorphine to a limited number of opiate-dependent patients. The sublingual tablets Subutex® (buprenorphine alone) and Suboxone® (a combination

Donald R. Wesson; David E. Smith

2010-01-01

4

Buprenorphine: An Alternative Treatment for Opioid Dependence.  

National Technical Information Service (NTIS)

The publication discusses the metabolism and kinetics, clinical efficacy and safety, behavioral pharmacology, and effects in animals and humans of buprenorphine, an alternative treatment for opioid dependence.

J. D. Blaine

1992-01-01

5

Determinants of buprenorphine treatment for opioid dependence.  

PubMed

This study assessed the social, demographic and clinical determinants of whether an opioid-dependent patient received buprenorphine versus an alternative therapy. A retrospective cohort analysis of opioid-dependent adults enrolled in Group Health Cooperative between January 1, 2006 and December 1, 2010 was performed. Increasing the number of physicians with DATA waivers in a region and living in a relatively-populated area increased the likelihood of being treated with buprenorphine, indicating that lack of access is a potential barrier. Comorbidity also appeared to be a factor in receipt of treatment, with the effect varying by diagnosis. Finally, patients with an insurance plan allowing health services to be sought from any provider, with increased cost sharing, were significantly more likely to receive buprenorphine, implying that patient demand is a factor. Programs integrating patient education, physician training, and support from addiction specialists would be likely facilitators of increasing access to this cost-effective treatment. PMID:24209382

Murphy, Sean M; Fishman, Paul A; McPherson, Sterling; Dyck, Dennis G; Roll, John R

2014-03-01

6

Smoking cessation treatment among office-based buprenorphine treatment patients.  

PubMed

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 43.9years; 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. PMID:24912863

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

2014-08-01

7

Medication-assisted treatment for opioid addiction: methadone and buprenorphine  

PubMed Central

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

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

2013-01-01

8

Urine naloxone concentration at different phases of buprenorphine maintenance treatment.  

PubMed

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

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

2014-03-01

9

Emerging adult age status predicts poor buprenorphine treatment retention.  

PubMed

Emerging adults (18-25years old) are often poorly retained in substance use disorder treatment. Office-based buprenorphine often enhances treatment retention among people with opioid dependence. In this study, we examined the records of a collaborative care buprenorphine treatment program to compare the treatment retention rates of emerging adults versus older adults. Subjects were 294 adults, 71 (24%) aged 18-25, followed in treatment with buprenorphine, nurse care management, and an intensive outpatient program followed by weekly psychosocial treatment. Compared to older adults, emerging adults remained in treatment at a significantly lower rate at 3months (56% versus 78%) and 12months (17% versus 45%), and were significantly more likely to test positive for illicit opioids, relapse, or drop out of treatment. Further research into factors associated with buprenorphine treatment retention among emerging adults is needed to improve treatment and long-term outcomes in this group. PMID:24953168

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

2014-09-01

10

Retention in methadone and buprenorphine treatment among African Americans.  

PubMed

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

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

2013-09-01

11

Buprenorphine  

PubMed Central

In the crystal structure of a semi-synthetic opioid drug buprenorphine, C29H41NO4 {systematic name: (2S)-2-[(5R,6R,7R,14S)-9?-cyclo­propyl­methyl-3-hy­droxy-6-meth­oxy-4,5-ep­oxy-6,14-ethano­morphinan-7-yl]-3,3-di­methyl­butan-2-ol}, the cyclo­propyl­methyl group is disordered over two sites with an occupancy factor of 0.611?(3) for the major component. One of the hy­droxy groups is involved in intra­molecular O—H?O hydrogen bond. The other hy­droxy group acts as a proton donor in an inter­molecular O—H?O inter­action that connects mol­ecules into a zigzag chain along the b axis.

Mazurek, Jaroslaw; Hoffmann, Marcel; Fernandez Casares, Anna; Cox, Phillip D.; Minardi, Mathew D.

2014-01-01

12

Buprenorphine.  

PubMed

In the crystal structure of a semi-synthetic opioid drug buprenorphine, C29H41NO4 {systematic name: (2S)-2-[(5R,6R,7R,14S)-9?-cyclo-propyl-methyl-3-hy-droxy-6-meth-oxy-4,5-ep-oxy-6,14-ethano-morphinan-7-yl]-3,3-di-methyl-butan-2-ol}, the cyclo-propyl-methyl group is disordered over two sites with an occupancy factor of 0.611?(3) for the major component. One of the hy-droxy groups is involved in intra-molecular O-H?O hydrogen bond. The other hy-droxy group acts as a proton donor in an inter-molecular O-H?O inter-action that connects mol-ecules into a zigzag chain along the b axis. PMID:24940223

Mazurek, Jaroslaw; Hoffmann, Marcel; Fernandez Casares, Anna; Cox, Phillip D; Minardi, Mathew D

2014-06-01

13

Hypogonadism in men receiving methadone and buprenorphine maintenance treatment.  

PubMed

The aim of this study was to determine the prevalence and investigate the aetiology of hypogonadism in men on methadone or buprenorphine maintenance treatment (MMT, BMT). 103 men (mean age 37.6 +/- 7.9) on MMT (n = 84) or BMT (n = 19) were evaluated using hormone assays, body mass index (BMI), serological, biochemical, demographic and substance use measures. Overall 54% of men (methadone 65%; buprenorphine 28%) had total testosterone (TT) <12.0 nm; 34% (methadone 39%; buprenorphine 11%) had TT <8.0 nm. Both methadone- and buprenorphine-treated men had lower free testosterone, luteinising hormone and estradiol than age-matched reference groups. Methadone-treated men had lower TT than buprenorphine-treated men and reference groups. Prolactin did not differ between methadone, buprenorphine groups, and reference groups. Primary testicular failure was an uncommon cause of hypogonadism. Yearly percentage fall in TT by age across the patient group was 2.3%, more than twice that expected normally. There were no associations between TT and opioid dose, cannabis, alcohol and tobacco consumption, or chronic hepatitis C viraemia. On multiple regression higher TT was associated with higher alanine aminotransferase and lower TT with higher BMI. Men on MMT have high prevalence of hypogonadotrophic hypogonadism. The extent of hormonal changes associated with buprenorphine needs to be explored further in larger studies. Men receiving long term opioid replacement treatment, especially methadone treatment, should be screened for hypogonadism. Wide interindividual differences in methadone metabolism and tolerance may in a cross-sectional study obscure a methadone dose relationship to testosterone in individuals. Future studies of hypogonadism in opioid-treated men should examine the potential benefits of dose reduction, choice of opioid medication, weight loss, and androgen replacement. PMID:17971165

Hallinan, R; Byrne, A; Agho, K; McMahon, C G; Tynan, P; Attia, J

2009-04-01

14

Buprenorphine diffusion: the attitudes of substance abuse treatment counselors  

Microsoft Academic Search

In October 2002, the Food and Drug Administration approved buprenorphine for use in the treatment of opioid dependence. Successful diffusion, adoption, and implementation of this medication within the treatment field depend in part on substance abuse counselors. Using questionnaire data obtained from 2,298 counselors in community-based treatment programs in the private and public sectors between June 2002 and July 2004,

Hannah K. Knudsen; Lori J. Ducharme; Paul M. Roman; Tanja Link

2005-01-01

15

Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse  

Microsoft Academic Search

BACKGROUND: Buprenorphine, a partial mu-agonist and kappa-antagonist, has been proposed as an alternative to methadone for maintenance treatment of opioid dependence, especially for patients with concurrent cocaine dependence or abuse. This study evaluated whether higher maintenance doses of buprenorphine and methadone are superior to lower doses for reducing illicit opioid use and whether buprenorphine is superior to methadone for reducing

Richard S. Schottenfeld; Juliana Pakes; Alison Oliveto; Douglas M. Ziedonis; Thomas R. Kosten

1997-01-01

16

Short-term buprenorphine maintenance: treatment outcome.  

PubMed

Fifty-two heroin addicts were inducted onto buprenorphine under the care of psychiatric residents in a setting modeled on office practice. Subjects were maintained on a protocol of six weeks of 16 mg daily dosing, then tapered to zero dose up to week 16, and maintained on placebo through week 18. Of 44 subjects who continued after the first induction dose, 11 terminated during maintenance, 17 during taper; and 16 while on zero dose. Twice weekly urine toxicologies showed significant successive declines in samples positive for heroin use across these three periods: 70%, 41%, and 20%, respectively. Among historical variables, only prior AA attendance distinguished subjects who achieved zero dose from those who did not. A comparison with recent studies suggests that relatively inexperienced office-based physicians can maintain patients on buprenorphine at a level comparable to that reported for research clinic settings, but with comparable rates of heroin abstinence. These findings are discussed in light of potential options for office-based opioid maintenance. PMID:14621343

Galanter, Marc; Dermatis, Helen; Resnick, Richard; Maslansky, Robert; Neumann, Erna

2003-01-01

17

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

PubMed Central

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.

2014-01-01

18

Early adoption of buprenorphine in substance abuse treatment centers: Data from the private and public sectors  

Microsoft Academic Search

The recent approval of buprenorphine for the treatment of opiate dependence offers an opportunity to analyze innovation adoption in community-based treatment. Using data collected from national samples of 299 privately funded and 277 publicly funded treatment centers, this research examines buprenorphine adoption using baseline data collected between 2002 and 2004 as well as follow-up data collected 12 months later. Private

Hannah K. Knudsen; Lori J. Ducharme; Paul M. Roman

2006-01-01

19

The Physician Clinical Support System-Buprenorphine (PCSS-B): a novel project to expand/improve buprenorphine treatment.  

PubMed

Opioid dependence is largely an undertreated medical condition in the United States. The introduction of buprenorphine has created the potential to expand access to and use of opioid agonist treatment in generalist settings. Physicians, however, often have limited training and experience providing this type of care. Some physicians believe having a mentoring relationship with an experienced provider during their initial introduction to the use of buprenorphine would ease implementation. Our goal was to describe the development, implementation, resources, and evaluation of the Physician Clinical Support System-Buprenorphine (PCSS-B), a federally funded program to improve access to and quality of treatment with buprenorphine. We provide a description of the PCSS-B, a national network of 88 trained physician mentors with expertise in buprenorphine treatment and skills in clinical education. We provide information regarding the use the PCSS-B core services including telephone, email and in-person support, a website, clinical guidances, a warmline and outreach to primary care and specialty organizations. Between July 2005 and July 2009, 67 mentors and 4 clinical experts reported providing mentoring services to 632 participants in 48 states, Washington DC and Puerto Rico. A total of 1,455 contacts were provided through email (45%), telephone (34%) and in-person visits (20%). Seventy-six percent of contacts addressed a clinical issue. Eighteen percent of contacts addressed a logistical issue. The number of contacts per participant ranged from 1-125. Between August 2005 and April 2009 there were 72,822 visits to the PCSS-B website with 179,678 pages viewed. Seven guidances were downloaded more than 1000 times. The warmline averaged more than 100 calls per month. The PCSS-B model provides support for a mentorship program to assist non-specialty physicians in the provision of buprenorphine and may serve as a model for dissemination of other types of care. PMID:20458550

Egan, James E; Casadonte, Paul; Gartenmann, Tracy; Martin, Judith; McCance-Katz, Elinore F; Netherland, Julie; Renner, John A; Weiss, Linda; Saxon, Andrew J; Fiellin, David A

2010-09-01

20

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

PubMed Central

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.

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

21

Using buprenorphine short-term taper to facilitate early treatment engagement  

Microsoft Academic Search

The U.S. Federal Food and Drug Administration approved buprenorphine for drug abuse treatment in 2002, and it became available for clinical use in early 2003. Maryhaven, a community treatment program, participated in a National Institute on Drug Abuse Clinical Trials Network trial evaluating buprenorphine–naloxone (BNX; Suboxone) short-term taper for medically managed opioid withdrawal and later adopted this treatment. In a

Gregory S. Brigham; Leslie Amass; Theresa Winhusen; Judy M. Harrer; Alvin Pelt

2007-01-01

22

Clinical efficacy of buprenorphine: comparisons to methadone and placebo  

Microsoft Academic Search

Buprenorphine has been studied extensively since 1978 when it was initially proposed as an alternative to methadone for treatment of opioid dependence. Early work by Jasinski, Mello, Mendelson and their colleagues demonstrated buprenorphine's low physical abuse potential and its ability to substitute for heroin and reduce heroin self-administration in opiate-dependent humans. The subsequent early clinical studies suggested that, in clinical

Walter Ling; Donald R Wesson

2003-01-01

23

Deaths involving buprenorphine: a compendium of French cases  

Microsoft Academic Search

Buprenorphine at high dosage became available in France in 1996, as a substitution treatment for heroin addicts. Since this date, numerous deaths were attributed to this drug. This paper reports two original series of 39 and 78 fatalities involving buprenorphine observed at the Institute of Legal Medicine of Strasbourg and at 13 other French forensic centers, respectively. The files were

P. Kintz

2001-01-01

24

Drug Treatment Outcomes among HIV-Infected Opioid Dependent Patients Receiving Buprenorphine/naloxone  

PubMed Central

Background Buprenorphine/naloxone allows the integration of opioid dependence and HIV treatment. Methods We conducted a prospective study in HIV-infected opioid dependent patients to investigate the impact of buprenorphine/naloxone treatment on drug use. Self-report and chart review assessments were conducted every 3 months (Quarters 1 through 4) for one year. Outcomes were buprenorphine/naloxone treatment retention, drug use, and addiction treatment processes. Results Among 303 patients enrolled between July 2005 and December 2007, retention in buprenorphine/naloxone treatment was 74%, 67%, 59% and 49% during Quarters 1,2 3, and 4, respectively. Past 30 day illicit opioid use decreased from 84% of patients at baseline to 42% in retained patients over the year. Patients were 52% less likely to use illicit opioids for each quarter in treatment (OR = .66; 95% CI 0.61–0.72). Buprenorphine/naloxone doses and office visits approximated guidelines published by the United States Department of Health and Human Services. Urine toxicology monitoring was less frequent than recommended. Conclusions Buprenorphine/naloxone provided in HIV treatment settings can decrease opioid use. Strategies are needed to improve retention and address ongoing drug use in this treatment population.

Fiellin, David A.; Weiss, Linda; Botsko, Michael; Egan, James E; Altice, Frederick L.; Bazerman, Lauri B.; Chaudhry, Amina; Cunningham, Chinazo O.; Gourevitch, Marc N.; Lum, Paula J.; Sullivan, Lynn E.; Schottenfeld, Richard S.; O'Connor, Patrick G.

2013-01-01

25

Methadone versus buprenorphine maintenance for the treatment of heroin-dependent outpatients  

Microsoft Academic Search

The aim of this study was to assess the efficacy of methadone compared with buprenorphine maintenance therapy in heroin-dependent patients over a treatment period of 18 weeks. Subjects were randomized to receive either methadone or buprenorphine in a comparative double-blind study and consisted of 164 heroin-dependent male patients who met the DSM-IV criteria for heroin dependence and were seeking treatment.

Jamshid Ahmadi

2003-01-01

26

Impact of research network participation on the adoption of buprenorphine for substance abuse treatment.  

PubMed

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 1203 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

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

2014-05-01

27

Urinary Excretion of Buprenorphine, Norbuprenorphine, Buprenorphine-Glucuronide, and Norbuprenorphine-Glucuronide in Pregnant Women Receiving Buprenorphine Maintenance Treatment  

PubMed Central

BACKGROUND Buprenorphine (BUP) is under investigation as a medication therapy for opioid-dependent pregnant women. We investigated BUP and metabolite disposition in urine from women maintained on BUP during the second and third trimesters of pregnancy and postpartum. METHODS We measured BUP, norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and NBUP-Gluc concentrations in 515 urine specimens collected thrice weekly from 9 women during pregnancy and postpartum. Specimens were analyzed using a fully validated liquid chromatography-mass spectrometry method with limits of quantification of 5 µg/L for BUP and BUP-Gluc and 25 µg/L for NBUP and its conjugated metabolite. We examined ratios of metabolites across trimesters and postpartum to identify possible changes in metabolism during pregnancy. RESULTS NBUP-Gluc was the primary metabolite identified in urine and exceeded BUP-Gluc concentrations in 99% of specimens. Whereas BUP-Gluc was identified in more specimens than NBUP, NBUP exceeded BUP-Gluc concentrations in 77.9% of specimens that contained both analytes. Among all participants, the mean BUP-Gluc:NBUP-Gluc ratio was significantly higher in the second trimester compared to the third trimester, and there were significant intrasubject differences between trimesters in 71% of participants. In 3 women, the percent daily dose excreted was higher during pregnancy than postpregnancy, consistent with other data indicating increased renal elimination of drugs during pregnancy. CONCLUSIONS These data are the first to evaluate urinary disposition of BUP and metabolites in a cohort of pregnant women. Variable BUP excretion during pregnancy may indicate metabolic changes requiring dose adjustment during later stages of gestation.

Kacinko, Sherri L.; Jones, Hendree E.; Johnson, Rolley E.; Choo, Robin E.; Concheiro-Guisan, Marta; Huestis, Marilyn A.

2011-01-01

28

Preference for buprenorphine\\/naloxone and buprenorphine among patients receiving buprenorphine maintenance therapy in France: A prospective, multicenter study  

Microsoft Academic Search

Maintenance treatment with buprenorphine tablets (Subutex) has been associated with reductions in heroin use; however, concerns for intravenous misuse exist. A buprenorphine\\/naloxone formulation (Suboxone) was designed to reduce this misuse risk while retaining buprenorphine's efficacy and safety. This prospective, open-label, multicenter trial compared preferences for buprenorphine and buprenorphine\\/naloxone in 53 opioid-dependent patients stabilized on buprenorphine. Buprenorphine was first administered at

Jean-Pierre Daulouède; Yves Caer; Pascal Galland; Pierre Villeger; Emmanuel Brunelle; Jérôme Bachellier; Jean-Michel Piquet; Jean Harbonnier; Yves Leglise; Pascal Courty

2010-01-01

29

Buprenorphine treatment outcome in dually diagnosed heroin dependent patients: A retrospective study  

Microsoft Academic Search

The present study compared retrospectively in a clinical non-experimental setting the efficacy of buprenorphine (BUP) in different subgroups of dually diagnosed and non-dually diagnosed opioid-dependent patients: all the subjects included in the study showed severe long-lasting heroin addiction and 68.4% were affected by psychiatric comorbidity. Participants (206) (mean age 32.2±8.9, 177 males–29 females) were applicants to a long-term buprenorphine treatment

Gilberto Gerra; Claudio Leonardi; Antonio D'Amore; Giovanni Strepparola; Roberto Fagetti; Cinzia Assi; Amir Zaimovic; Alfio Lucchini

2006-01-01

30

Factors associated with the prescribing of buprenorphine or methadone for treatment of opiate dependence.  

PubMed

The study investigates patient preferences and beliefs and treatment program factors related to the decision to prescribe either buprenorphine or methadone to opiate-dependent patients. The sample (N = 192) was recruited from 10 addiction treatment services in London. Data were collected by means of a single structured interview conducted with patients commencing a treatment episode at the participating agencies. Data on patient demographics, beliefs, attitudes, and preferences were collected using a structured interview. Data regarding treatment goals and prescribed medication were collected from interviews with clinical staff. Oral methadone had a higher preference rating than buprenorphine. Clinical prescribing practices were influenced by patient preferences (both positive and negative), by prior treatment experiences, and by current treatment goals. Patient preferences and beliefs about opioid agonist medications served as an important influence upon clinical prescribing practices. The odds of being prescribed buprenorphine were three times greater among those patients who reported a preference for buprenorphine. The odds of receiving a prescription for methadone were about twice as great among those for whom methadone was the more preferred medication. Preferences were related to previous treatment experiences with these opioid agonists, and for patients in both groups, personal experience was the most important source of information about the treatment options. Buprenorphine was more likely to be prescribed for short-term detoxification and methadone for maintenance treatment. PMID:19004598

Ridge, Gayle; Gossop, Michael; Lintzeris, Nicholas; Witton, John; Strang, John

2009-07-01

31

Counselor Attitudes toward the Use of Buprenorphine in Substance Abuse Treatment: A Multi-level Modeling Approach  

PubMed Central

In spite of evidence that buprenorphine is effective, safe, and offers greater access as compared with methadone, implementation for treatment of opiate dependence continues to be weak. Research indicates that legal and regulatory factors, state policies, and organizational and provider variables affect adoption of buprenorphine. This study uses hierarchical linear modeling (HLM) to examine National Treatment Center Study (NTCS) data to identify counselor characteristics (attitudes, training, beliefs) and organizational factors (accreditation, caseload, access to buprenorphine and other evidence-based practices) that influence implementation of buprenorphine for treatment of opiate dependence. Analyses showed that provider training about buprenorphine, higher prevalence of opiate dependent clients, and less treatment program emphasis on a 12-step model predicted greater counselor acceptance and perceived effectiveness of buprenorphine. Results also indicate that program use of buprenorphine for any treatment purpose (detoxification, maintenance, and/or pain management) and time (calendar year in data collection) were associated with increased diffusion of knowledge about buprenorphine among counselors and with more favorable counselor attitudes toward buprenorphine.

Kovas, Anne E.; McFarland, Bentson H.; Abraham, Amanda J.

2012-01-01

32

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

PubMed Central

Context The usual treatment for opioid-addicted youth is detoxification and counseling. Extended medication-assisted therapy may be more helpful. Objective To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth. Design, Setting, and Patients Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine-naloxone or a 14-day taper (detox). Interventions Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling. Main Outcome Measure Opioid-positive urine test result at weeks 4, 8, and 12. Results The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 ( ?22 = 4.93, P = .09). At week 4, 59 detox patients had positive results (61%; 95% confidence interval [CI] = 47%-75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI = 14%-38%). At week 8, 53 detox patients had positive results (54%; 95% CI = 38%-70%) vs 52 12-week buprenorphine-naloxone patients (23%; 95% CI = 11%-35%). At week 12, 53 detox patients had positive results (51%; 95% CI = 35%-67%) vs 49 12-week buprenorphine-naloxone patients (43%; 95% CI = 29%-57%). By week 12, 16 of 78 detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients (70%; ?12 = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine-naloxone group reported less opioid use ( ?12 = 18.45, P < .001), less injecting ( ?12 = 6.00, P = .01), and less nonstudy addiction treatment ( ?12 = 25.82, P < .001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12. Conclusions Continuing treatment with buprenorphine-naloxone improved outcome compared with short-term detoxification. Further research is necessary to assess the efficacy and safety of longer-term treatment with buprenorphine for young individuals with opioid dependence.

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

2008-01-01

33

State policy influence on the early diffusion of buprenorphine in community treatment programs  

PubMed Central

Background Buprenorphine was approved for use in the treatment of opioid dependence in 2002, but its diffusion into everyday clinical practice in community-based treatment programs has been slow. This study examines the net impact of efforts by state agencies, including provision of Medicaid coverage, on program-level adoption of buprenorphine as of 2006. Methods Interviews were conducted with key informants in 49 of the 50 state agencies with oversight responsibility for addiction treatment services. Information from these interviews was integrated with organizational data from the 2006 National Survey of Substance Abuse Treatment Services. A multivariate logistic regression model was estimated to identify the effects of state efforts to promote the use of this medication, net of a host of organizational characteristics. Results The availability of Medicaid coverage for buprenorphine was a significant predictor of its adoption by treatment organizations. Conclusion Inclusion of buprenorphine on state Medicaid formularies appears to be a key element in ensuring that patients have access to this state-of-the-art treatment option. Other potential barriers to the diffusion of buprenorphine require identification, and the value of additional state-level policies to promote its use should be evaluated.

Ducharme, Lori J; Abraham, Amanda J

2008-01-01

34

A multi-level analysis of counselor attitudes toward the use of buprenorphine in substance abuse treatment  

Microsoft Academic Search

Despite evidence that buprenorphine is effective and safe and offers greater access as compared with methadone, implementation for treatment of opiate dependence continues to be weak. Research indicates that legal and regulatory factors, state policies, and organizational and provider variables affect adoption of buprenorphine. This study uses hierarchical linear modeling to examine National Treatment Center Study data to identify counselor

Traci R. Rieckmann; Anne E. Kovas; Bentson H. McFarland; Amanda J. Abraham

2011-01-01

35

Improved Buprenorphine Immunoassay Performance After Urine Treatment with ?-Glucuronidase.  

PubMed

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 ?-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

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

2014-07-01

36

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

PubMed

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

Newman, Robert G; Gevertz, Susan G

2013-01-01

37

Cognitive functioning during methadone and buprenorphine treatment: results of a randomized clinical trial.  

PubMed

Cognitive impairment in drug-dependent patients receiving methadone (MMP) maintenance treatment has been reported previously. We assessed cognitive functioning after at least 14 days of stable substitution treatment with buprenorphine (BUP) or MMP and after 8 to 10 weeks. We performed a randomized, nonblinded clinical trial in 59 drug-dependent patients receiving either BUP or MMP maintenance treatment and healthy normal controls (n = 24) matched for sex, age, and educational level. Thirteen patients dropped out of the study before the second testing was performed (BUP, n = 22; MMP, n = 24). A neuropsychological test battery was used to measure selective attention, verbal memory, motor/cognitive speed, and cognitive flexibility. In addition, subjective perceived stress was assessed with a questionnaire. Patients in both treatment groups performed equally well in all of the cognitive domains tested. Both BUP and MMP patients showed significantly improved concentration and executive functions after 8 to 10 weeks of stable substitution treatment. The control group achieved better results than the BUP and MMP groups in most cognitive domains, indicating cognitive impairment in the patients. Perceived stress did not show any significant change after 8 to 10 weeks of treatment, and no major differences were detected between the 3 groups. No effects of perceived stress on cognitive function were found. Our results indicate a cognitive impairment in patients receiving maintenance treatment with BUP or MMP compared with healthy controls. Selective attention improved in both patient groups during treatment. We propose that the improvement of attention may facilitate rehabilitation of drug-dependent patients. PMID:19011441

Soyka, Michael; Lieb, Martin; Kagerer, Sabine; Zingg, Christina; Koller, Gabriele; Lehnert, Peter; Limmer, Claudia; Kuefner, Heinrich; Hennig-Fast, Kristina

2008-12-01

38

Developing and Implementing a New Prison-Based Buprenorphine Treatment Program  

ERIC Educational Resources Information Center

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…

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

2010-01-01

39

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

PubMed

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 ?= 10.55;?p?< .001). Neither demographics nor baseline ASI composite scores were predictive of relapse (p's > .05). Compliance with medication-assisted treatment supports abstinence, essential for patient recovery. Understanding the factors that drive treatment compliance and noncompliance may assist providers in supporting patient compliance and recovery.? PMID:22211347

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

2012-01-01

40

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

ERIC Educational Resources Information Center

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…

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

2004-01-01

41

Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers  

PubMed Central

BACKGROUND Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, crossover study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs). METHODS Intravenous heroin users (n=12) lived in the hospital for 8–9 weeks and were maintained on each of 3 different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin, and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the 3 buprenorphine maintenance dose conditions. RESULTS Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of “drug liking” and “desire to take the drug again” were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient. CONCLUSIONS These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, it is lower than for buprenorphine alone, particularly when participants received higher maintenance dosages and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment.

Comer, Sandra D.; Sullivan, Maria A.; Vosburg, Suzanne K.; Manubay, Jeanne; Amass, Leslie; Cooper, Ziva D.; Saccone, Phillip; Kleber, Herbert D.

2012-01-01

42

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

Microsoft Academic Search

To examine the influence of top managers’ characteristics on the adoption of buprenorphine for opioid dependence among U.S.\\u000a outpatient substance abuse treatment units, this investigation analyzed a cross-sectional national study of 547 such units\\u000a in the 2004–2005 wave of the Drug Abuse Treatment System Survey. Administrators reported their demographics, training, and\\u000a treatment orientation, as well as features of the unit

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

2010-01-01

43

Buprenorphine adoption in the National Drug Abuse Treatment Clinical Trials Network  

Microsoft Academic Search

The National Drug Abuse Treatment Clinical Trials Network (CTN), a collaborative federal research initiative that brings together universities and community-based treatment programs (CTPs), has conducted multiple clinical trials of buprenorphine for opioid dependence. Part of the CTN's mission is to promote the adoption of evidence-based treatment technologies. Drawing on a data collected during face-to-face interviews with administrators from a panel

Hannah K. Knudsen; Amanda J. Abraham; J. Aaron Johnson; Paul M. Roman

2009-01-01

44

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

PubMed

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. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24817054

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

2014-06-01

45

Criminal charges prior to and after initiation of office-based buprenorphine treatment  

PubMed Central

Background There is little data on the impact of office-based buprenorphine therapy on criminal activity. The goal of this study was to determine the impact of primary care clinic-based buprenorphine maintenance therapy on rates of criminal charges and the factors associated with criminal charges in the 2 years after initiation of treatment. Methods We collected demographic and outcome data on 252 patients who were given at least one prescription for buprenorphine. We searched a public database of criminal charges and recorded criminal charges prior to and after enrollment. We compared the total number of criminal cases and drug cases 2 years before versus 2 years after initiation of treatment. Results There was at least one criminal charge made against 38% of the subjects in the 2 years after initiation of treatment; these subjects were more likely to have used heroin, to have injected drugs, to have had any prior criminal charges, and recent criminal charges. There was no significant difference in the number of subjects with any criminal charge or a drug charge before and after initiation of treatment. Likewise, the mean number of all cases and drug cases was not significantly different between the two periods. However, among those who were opioid-negative for 6 or more months in the first year of treatment, there was a significant decline in criminal cases. On multivariable analysis, having recent criminal charges was significantly associated with criminal charges after initiation of treatment (adjusted odds ratio 3.92); subjects who were on opioid maintenance treatment prior to enrollment were significantly less likely to have subsequent criminal charges (adjusted odds ratio 0.52). Conclusions Among subjects with prior criminal charges, initiation of office-based buprenorphine treatment did not appear to have a significant impact on subsequent criminal charges.

2012-01-01

46

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

Microsoft Academic Search

The present study compared in a clinical non-experimental setting the efficacy of buprenorphine (BUP) and methadone (METH) in the treatment of opioid dependence: all the subjects included in the study showed severe long-lasting heroin addiction. Participants (154) were applicants to a 12 weeks treatment program, who were assigned to either METH (78) (mean doses 81.5±36.4mg) or BUP (76) (mean doses

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

2004-01-01

47

A randomized trial of intensive outpatient (IOP) vs. standard outpatient (OP) buprenorphine treatment for African Americans  

PubMed Central

BACKGROUND Buprenorphine is increasingly being used in community-based treatment programs, but little is known about the optimal level of psychosocial counseling in these settings. The aim of this study was to compare the effectiveness of OP and IOP level counseling when provided as part of buprenorphine treatment for opioid-dependent African Americans. METHODS Participants were African American men and women starting buprenorphine treatment at one of two community-based clinics (N=300). Participants were randomly assigned to OP or IOP. Measures at baseline, 3- and 6-months included the primary outcome of DSM-IV opioid and cocaine dependence criteria, as well as additional outcomes of illicit opioid and cocaine use (urine test and self-report), criminal activity, retention in treatment, Quality of Life, Addiction Severity Index composite scores, and HIV risk behaviors. RESULTS Participants assigned to OP received, on average, 3.67 (SD=1.30) hours of counseling per active week in treatment. IOP participants received an average of 5.23 (SD=1.68) hours of counseling per active week (less than the anticipated 9 hours per week of counseling). Both groups showed substantial improvement over a 6-month period on nearly all measures considered. There were no significant differences between groups in meeting diagnostic criteria for opioid (p=.67) or cocaine dependence (p=.63). There were no significant between group differences on any of the other outcomes. A secondary analysis restricting the sample to participants meeting DSM-IV criteria for baseline cocaine dependence also revealed no significant between-group differences (all ps>.05). CONCLUSIONS Buprenorphine patients receiving OP and IOP levels of care both show short-term improvements.

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

2012-01-01

48

Suboxone® (Buprenorphine\\/Naloxone) as an Agonist Opioid Treatment in Spain: A Budgetary Impact Analysis  

Microsoft Academic Search

Objective: To evaluate the economic impact of buprenorphine\\/naloxone (B\\/N) as an agonist opioid treatment for opiate dependence. Methods: A budgetary impact analysis model was designed to calculate the annual costs (drugs and associated costs) to the Spanish National Healthcare System of methadone versus B\\/N. Data for the model were obtained from official databases and expert panel opinion. Results: It was

José Martínez-Raga; Francisco González Saiz; César Pascual; Miguel A. Casado; Francisco J. Sabater Torres

2010-01-01

49

A placebo controlled clinical trial of buprenorphine as a treatment for opioid dependence  

Microsoft Academic Search

Large-scale placebo controlled clinical trials assessing the efficacy of medications for the treatment of drug dependence have generally been limited to alcohol, cocaine and nicotine dependent populations. The purpose of the present study was to assess the early (1–2 week) clinical effectiveness of buprenorphine versus placebo in an opioid dependent population. The study used a parallel-group design with a behavioral

Rolley E. Johnson; Thomas Eissenberg; Maxine L. Stitzer; Eric C. Strain; Ira A. Liebson; George E. Bigelow

1995-01-01

50

Reversal of Sleep Disturbances in Cocaine-and Heroin-Dependent Men During Chronic Buprenorphine Treatment  

Microsoft Academic Search

Changes in sleep architecture and continuity are frequent side effects of drugs of abuse, and complaints of poor sleep are often reported by recovering drug abusers. As part of a Phase 1 assessment of the safety and efficacy of 4 and 8 mg\\/day of buprenorphine treatment, the sleep patterns of 20 male opiate-and cocaine-dependent patients were quantified by using standard

Scott E. Lukas; Cynthia M. Dorsey; Nancy K. Mello; Jack H. Mendelson; Leslie H. Lundahl; Michelle Sholar; Steven L. Cunningham

1996-01-01

51

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

PubMed

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

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

2014-01-01

52

Effects of buprenorphine versus buprenorphine\\/naloxone tablets in non-dependent opioid abusers  

Microsoft Academic Search

Rationale: Buprenorphine is an opioid agonist-antagonist under development in the United States as a sublingual medication for treatment\\u000a of opioid dependence. Buprenorphine may be abused; therefore, tablets combining buprenorphine with naloxone have been developed\\u000a with the intent of reducing the abuse risk in people physically dependent upon opioids. The characteristics and abuse potential\\u000a of buprenorphine and buprenorphine\\/naloxone tablets in non-dependent

Eric C. Strain; Kenneth Stoller; Sharon L. Walsh; George E. Bigelow

2000-01-01

53

Heroin Dependence Treatment in Malaysia: A randomized, double-blind placebo-controlled comparison of buprenorphine and naltrexone maintenance treatment  

PubMed Central

Background Expanding access to effective treatments for heroin dependence is a global health priority that will also reduce HIV transmission. This study compares the efficacy for maintaining heroin abstinence, preventing relapse, and reducing HIV risk behaviors of three common treatments: detoxification followed by drug counseling only or drug counseling combined with opioid antagonist (naltrexone) or agonist (buprenorphine) maintenance treatment. Methods 126 detoxified heroin dependent patients in Malaysia were randomly assigned to 24 weeks of medication maintenance with naltrexone, buprenorphine, or placebo, provided double-blind and double-dummy. All patients received manual-guided drug counseling. Primary outcomes, assessed by three times per week urine testing, were days to first heroin use, days to heroin relapse (3 consecutive opioid-positive urine tests), maximum consecutive days heroin abstinence, and, assessed by self-report at baseline, 3- and 6-months, reductions in HIV risk behaviors. The study was terminated after 22 months of enrolment, based on findings of superior buprenorphine efficacy in an interim safety analysis and the recommendation of the Data and Safety Monitoring Board. This study is registered with ClinicalTrials.gov, with the number NCT00383045. Findings We observed consistent, significant linear contrasts in days to first heroin use (p<0.001), days to heroin relapse (p<0.001), maximum consecutive days heroin abstinence (p<0.01), and retention (p<0.001), with all results best for buprenorphine, intermediate for naltrexone, and worst for placebo. Buprenorphine was associated with significantly greater time to first heroin use and retention compared to naltrexone (p<0.01 for both measures) or placebo (p<0.001 for both measures) and also significantly greater time to heroin relapse (p<0.01) and maximum consecutive weeks abstinent (p<0.01) compared to placebo. There were no significant differences between naltrexone and placebo on these measures. HIV risk behaviors were significantly reduced from baseline across all 3 treatments (p<0.001), but the reductions did not differ significantly among the 3 treatments. Interpretation The effectiveness of buprenorphine for maintaining prolonged periods of abstinence, delaying the time to resumption of heroin use or relapse, and retaining patients in treatment supports widespread dissemination of opioid agonist maintenance treatment.

Schottenfeld, Richard S.; Chawarski, Marek C.; Mazlan, Mahmud

2011-01-01

54

Entry into primary care-based buprenorphine treatment is associated with identification and treatment of other chronic medical problems  

PubMed Central

Background Buprenorphine is an effective treatment for opioid dependence that can be provided in a primary care setting. Offering this treatment may also facilitate the identification and treatment of other chronic medical conditions. Methods We retrospectively reviewed the medical records of 168 patients who presented to a primary care clinic for treatment of opioid dependence and who received a prescription for sublingual buprenorphine within a month of their initial visit. Results Of the 168 new patients, 122 (73%) did not report having an established primary care provider at the time of the initial visit. One hundred and twenty-five patients (74%) reported at least one established chronic condition at the initial visit. Of the 215 established diagnoses documented on the initial visit, 146 (68%) were not being actively treated; treatment was initiated for 70 (48%) of these within one year. At least one new chronic medical condition was identified in 47 patients (28%) during the first four months of their care. Treatment was initiated for 39 of the 54 new diagnoses (72%) within the first year. Conclusions Offering treatment for opioid dependence with buprenorphine in a primary care practice is associated with the identification and treatment of other chronic medical conditions.

2012-01-01

55

[Buprenorphine transdermal patch (Norspan tape)].  

PubMed

Buprenorphine is a chemically synthesized opioid characterized as the partial mu agonist and kappa antagonist, and transdermal buprenorphine patch will be considered useful as a strong analgesic with fewer psychological side effects in the treatment of chronic non-cancer pain. Use of transdermal buprenorphine should be limited for pain relief of intractable muscle skeletal pain that cannot be alleviated with other analgesics. To avoid severe complication and drug abuse or addiction, assessment of pain and medical history including drug dependence by medical team are important before administration of transdermal buprenorphine. Moreover, side effects such as nausea, vomiting, constipation, erythema and itching, loss of appetite should be treated appropriately. When transdermal buprenorphine is administered to chronic pain patients, physicians must examine the condition of patients regularly at an outpatient clinic. Moreover, decreasing and discontinuation of opioid including transdermal buprenorphine should always be considered during the treatment. Most important objective of chronic pain treatment is to improve QOL and ADL of patients. PMID:23905402

Hamaguchi, Shinsuke; Ikeda, Tomohito

2013-07-01

56

The effects of buprenorphine in buprenorphine-maintained volunteers  

Microsoft Academic Search

Buprenorphine is a mu opioid partial agonist currently used as an analgesic, and being developed for the treatment of opioid\\u000a dependence. The purpose of this study was to determine the abuse liability of parenteral buprenorphine in volunteers maintained\\u000a on daily sublingual (SL) buprenorphine (8?mg). In a residential laboratory, eight volunteers underwent pharmacologic challenges\\u000a two times per week. Medication challenges were

Eric C. Strain; Sharon L. Walsh; Kenzie L. Preston; Ira A. Liebson; George E. Bigelow

1997-01-01

57

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

PubMed

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

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

2013-08-01

58

The effect of buprenorphine and benzodiazepines on respiration in the rat.  

PubMed

Methadone and buprenorphine are the two main opioid substitution treatments for heroin dependence currently offered in Australia. A number of publications have implicated buprenorphine as being potentially dangerous in combination with benzodiazepines but no comparison has been made to the relative dangers of benzodiazepines combined with buprenorphine or methadone. The effect of i.v. methadone and buprenorphine on respiration was investigated by evaluating arterial blood pCO2, pO2 and pH, and measuring respiratory rate in rats. Measurements were taken at 0, 15, 30, 60, 120, 180 and 240 min after i.v. administration of methadone or buprenorphine. Effects on respiration were greatest 15 min after i.v. drug administration. The effect of methadone and buprenorphine on respiration was compared with and without diazepam pretreatment (20 mg/kg). Buprenorphine alone exhibited a bell shaped dose response inhibition of respiration; however the plateau of the dose response inhibition on respiration was lost when administered in combination with diazepam. Methadone showed a dose-dependent inhibitory effect on respiration, which was potentiated with diazepam pretreatment. While the effect of diazepam pretreatment was the abolishment of the protective bell shaped dose response effect on respiration, the effect of buprenorphine and diazepam was not greater than methadone and diazepam. PMID:15943948

Nielsen, Suzanne; Taylor, David A

2005-07-01

59

Facts about Buprenorphine for Treatment of Opioid Addiction  

MedlinePLUS

... in treatment. Through counseling, you learn about the motivations and behaviors that led to your opioid addiction. ... Counseling can provide you with encouragement and with motivation to stick to treatment. It can help you ...

60

Similarities and Differences in Opiod Treatment Programs that Provide Methadone Maintenance or Buprenorphine Maintenance. The N-SSATS Report.  

National Technical Information Service (NTIS)

The National Survey of Substance Abuse Treatment Services (N-SSATS) asks OTPs about their services. This report includes information about OTPs that responded to N-SSATS; it does not include data from private physicians who prescribe buprenorphine. This r...

2010-01-01

61

Buprenorphine: how to use it right  

Microsoft Academic Search

The unique pharmacology of buprenorphine at the mu-opioid receptor (i.e. high affinity, low intrinsic activity and slow dissociation) results in buprenorphine having: (1) a good safety profile, (2) low physical dependence, and (3) flexibility in dose scheduling. Early studies assessed the effectiveness of buprenorphine for the treatment of opioid dependence using a sublingual solution formulation. More recently, a combination tablet

Rolley E. Johnson; Eric C. Strain; Leslie Amass

2003-01-01

62

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

Microsoft Academic Search

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

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

2006-01-01

63

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

PubMed

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

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

64

Timing of buprenorphine adoption by privately funded substance abuse treatment programs: The role of institutional and resource-based interorganizational linkages  

Microsoft Academic Search

Identifying facilitators of more rapid buprenorphine adoption may increase access to this effective treatment for opioid dependence. Using a diffusion of innovations theoretical framework, we examine the extent to which programs' interorganizational institutional and resource-based linkages predict the likelihood of being an earlier adopter, later adopter, or nonadopter of buprenorphine. Data were derived from face-to-face interviews with administrators of 345

Sarah A. Savage; Amanda J. Abraham; Hannah K. Knudsen; Tanja C. Rothrauff; Paul M. Roman

65

Opioid Addiction and Abuse in Primary Care Practice: A Comparison of Methadone and Buprenorphine as Treatment Options  

PubMed Central

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, 200 000 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.

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

2014-01-01

66

Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome  

Microsoft Academic Search

This study was designed to compare the neonatal abstinence syndrome (NAS) in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and to provide preliminary safety and efficacy data for a larger multi-center trial. This randomized, double-blind, double-dummy, flexible dosing, parallel-group controlled trial was conducted in a comprehensive drug-treatment facility that included residential and ambulatory care. Participants were opioid-dependent pregnant

E. Jonesa; Rolley E. Johnsona; Donald R. Jasinskib; Kevin E. O'Gradyc; Christian A. Chisholmd; Robin E. Choof; Michael Crocettie; Robert Dudase; Cheryl Harrowe; Marilyn A. Huestisf; Lauren M. Janssone; Michael Lantzd; Barry M. Lesterg; Lorraine Miliod

67

Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth?  

PubMed Central

Background In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment. Methods Opioid dependent adolescents and young adults (n=152), aged 15–21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression. Results In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition. Conclusions Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/ Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics.

Warden, Diane; Subramaniam, Geetha A.; Carmody, Thomas; Woody, George E.; Minhajuddin, Abu; Poole, Sabrina A.; Potter, Jennifer; Fishman, Marc; Bogenschutz, Michael; Patkar, Ashwin; Trivedi, Madhukar H.

2012-01-01

68

Transdermal buprenorphine in the treatment of cancer and non-cancer pain - the results of multicenter studies in Poland.  

PubMed

This was a multicenter, non-interventional, post-marketing study that aimed to evaluate the analgesic activity, safety of use, safety profile and adverse drug reactions of transdermal buprenorphine (Transtec 35, 52.5 and 70 ?g/h) during the treatment of moderate to severe chronic cancer and non-cancer pain. The study was performed in Poland by 339 doctors. The study involved 4,030 general practice outpatients (managed by primary care physicians), pain therapy center patients, specialist outpatient clinic patients as well as patients treated in inpatients units. The recruitment process began in September of 2007, and the study was completed in October of 2008. The study has been reported to the Central Register of Clinical Trials in Poland; it was also in accordance with the requirements of the Polish Pharmaceutical Law in force. The objective of the study was to evaluate the efficacy, safety of use and application of transdermal buprenorphine in patients with moderate to severe cancer pain and in patients with severe, non-malignant pain in the course of other diseases. Patients were enrolled if their pain was not well-controlled after using non-opioid analgesics. Another objective of the study was to monitor adverse drug reactions of transdermal buprenorphine reported by patients or noted by the doctors during the study visits. This first such multicenter study in Poland has confirmed high efficacy and good tolerability of buprenorphine and, therefore, confirmed its usefulness in the treatment of moderate to severe cancer pain as well as in the treatment of severe pain in patients with non-cancer pain that cannot be effectively treated with non-opioid analgesics. PMID:22001981

Przeklasa-Muszy?ska, Anna; Dobrogowski, Jan

2011-01-01

69

Patient Characteristics Associated with Buprenorphine/Naloxone Treatment Outcome for Prescription Opioid Dependence: Results from a Multisite Study  

PubMed Central

Background Prescription opioid dependence is a growing problem, but little research exists on its treatment, including patient characteristics that predict treatment outcome. Methods A secondary analysis of data from a large multisite, randomized clinical trial, the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study (POATS) was undertaken to examine baseline patient characteristics (N=360) associated with success during 12-week buprenorphine/naloxone treatment for prescription opioid dependence. Baseline predictor variables included self-reported demographic and opioid use history information, diagnoses assessed via the Composite International Diagnostic Interview, and historical opioid use and related information from the Pain And Opiate Analgesic Use History. Results In bivariate analyses, pre-treatment characteristics associated with successful opioid use outcome included older age, past-year or lifetime diagnosis of major depressive disorder, initially obtaining opioids with a medical prescription to relieve pain, having only used opioids by swallowing or sublingual administration, never having used heroin, using an opioid other than extended-release oxycodone most frequently, and no prior opioid dependence treatment. In multivariate analysis, age, lifetime major depressive disorder, having only used opioids by swallowing or sublingual administration, and receiving no prior opioid dependence treatment remained as significant predictors of successful outcome. Conclusions This is the first study to examine characteristics associated with treatment outcome in patients dependent exclusively on prescription opioids. Characteristics associated with successful outcome after 12 weeks of buprenorphine/naloxone treatment include some that have previously been found to predict heroin-dependent patients’ response to methadone treatment and some specific to prescription opioid-dependent patients receiving buprenorphine/naloxone.

Dreifuss, Jessica A.; Griffin, Margaret L.; Frost, Katherine; Fitzmaurice, Garrett M.; Potter, Jennifer Sharpe; Fiellin, David A.; Selzer, Jeffrey; Hatch-Maillette, Mary; Sonne, Susan C.; Weiss, Roger D.

2012-01-01

70

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

PubMed Central

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.

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

2010-01-01

71

Effects of buprenorphine and methadone in methadone-maintained subjects  

Microsoft Academic Search

Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of a program to develop procedures for transferring patients from methadone to buprenorphine treatment. This laboratory study

S. L. Walsh; H. L. June; K. J. Schuh; K. L. Preston; G. E. Bigelow; M. L. Stitzer

1995-01-01

72

Buprenorphine maintenance therapy hinders acute pain management in trauma.  

PubMed

Buprenorphine is a mixed opiate receptor agonist-antagonist growing in popularity as an office-based treatment for opioid-dependent patients. It has high affinity, but only partial agonism at the micro-opioid receptor resulting in a ceiling analgesic effect. At higher doses, buprenorphine potentiates antagonism at the kappa-opioid receptor. These properties make buprenorphine an effective maintenance treatment for opioid-dependent patients. These same properties, however, can interfere with the management of acute pain in patients on maintenance buprenorphine therapy. We present a case of a young multisystem trauma patient in whom adequate analgesia could not be achieved due to buprenorphine treatment before and through the early course of admission. Discontinuation of buprenorphine allowed for appropriate pain management and successful analgesia. Further education of acute care clinicians about buprenorphine pharmacology and careful selection of patients for buprenorphine maintenance therapy are needed to avoid delays of pain control in trauma patients. PMID:20420250

Harrington, Colin J; Zaydfudim, Victor

2010-04-01

73

Clinical and pharmacological evaluation of buprenorphine and naloxone combinations: why the 4:1 ratio for treatment?  

Microsoft Academic Search

Although only a partial ?-opiate agonist, buprenorphine can be abused and diverted from medical therapy to the illicit drug market. A combination of buprenorphine and naloxone for sublingual administration may discourage diversion and abuse by precipitating opiate withdrawal when taken parenterally. Because opiate-abusing populations are not homogeneous and have varying levels of opiate dependence, the efficacy of buprenorphine and naloxone

John Mendelson; Reese T. Jones

2003-01-01

74

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

PubMed Central

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

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

2011-01-01

75

Tetanus in an Injecting Buprenorphine Abuser  

Microsoft Academic Search

Introduction: Injecting drug abusers are vulnerable to many infectious complications. We describe a case of tetanus in a Singaporean who regularly abused buprenorphine. Clinical Picture: A 49-year-old male was hospitalised for progressive generalised spasms associated with dysarthria and opisthotonus. Tetanus was diagnosed clinically. Treatment: Supportive management was instituted in the intensive care unit (ICU). Toxicology samples tested positive for buprenorphine.

Felicia SW Teo; Yang Hsu; Khim Nian; Sin Fai Lam; A Johan

76

Timing of buprenorphine adoption by privately funded substance abuse treatment programs: The role of institutional and resource-based inter-organizational linkages  

PubMed Central

Identifying facilitators of more rapid buprenorphine adoption may increase access to this effective treatment for opioid dependence. Using a diffusion of innovations theoretical framework, we examine the extent to which programs’ inter-organizational institutional and resource-based linkages predict the likelihood of being an earlier, later, or non-adopter of buprenorphine. Data were derived from face-to-face interviews with administrators of 345 privately funded substance abuse treatment programs in 2007–2008. Results of multinomial logistic regression models show that inter-organizational and resource linkages were associated with timing of adoption. Programs reporting membership in provider associations were more likely to be earlier adopters of buprenorphine. Programs that relied more on resources linkages, such as the detailing activities by pharmaceutical companies and the NIDA website, were more likely to be earlier adopters of buprenorphine. These findings suggest that institutional and resource-based inter-organizational linkages may expose programs to effective treatments, thereby facilitating more rapid and sustained adoption of innovative treatment techniques.

Savage, Sarah A.; Abraham, Amanda J.; Knudsen, Hannah K.; Rothrauff, Tanja C.; Roman, Paul M.

2011-01-01

77

Gender Differences Among Prisoners With Pre-Incarceration Heroin Dependence Participating in a Randomized Clinical Trial of Buprenorphine Treatment  

PubMed Central

The primary focus of the current study is to examine whether gender and other baseline characteristics were significantly associated with more severe patterns of drug use. It involves data from 260 male and female pre-release prison inmates with pre-incarceration heroin dependence who enrolled in a randomized clinical trial of prison-initiated buprenorphine. Three outcomes are examined: 1) Lifetime Intravenous drug use; 2) Lifetime number of drugs used; and 3) Heroin use in prison. Regarding lifetime intravenous drug use; race (p = .0001), education (p = .009), age (p = .0001), and psychological treatment (p = .028) were significant. Concerning lifetime number of drugs used; race (p =.0001) and age of first crime (p = .001) were significant. Finally, gender (p = .004), was the only significant variable in terms of using heroin while in prison. All of these differences may have important clinical, treatment, and research implications, which are discussed.

Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Wilson, Monique E.; Schwartz, Robert P.; O'Grady, Kevin E.

2013-01-01

78

Bioavailability of Buprenorphine from Crushed and Whole Buprenorphine (Subutex) Tablets  

Microsoft Academic Search

Background: Buprenorphine (Subutex) is the most abused opioid in Finland. In order to curb the abuse potential of this drug, many treatment centers and prisons crush Subutex tablets before administering them to patients. To date, there are no published studies comparing the efficacy and bioavailability of crushed and whole Subutex tablets. Methods: A total of 16 opioid-dependent patients stabilized on

Kaarlo Simojoki; Pirjo Lillsunde; Nicholas Lintzeris; Hannu Alho

2010-01-01

79

Buprenorphine-Naloxone Maintenance Following Release from Jail  

Microsoft Academic Search

Primary care is understudied as a re-entry drug and alcohol treatment setting. This study compared treatment retention and opioid misuse among opioid dependent adults seeking buprenorphine\\/naloxone maintenance in an urban primary care clinic following release from jail vs. community referrals. Post-release patients were either; a) induced to buprenorphine in-jail as part of a clinical trial, or, b) seeking buprenorphine induction

Joshua D. Lee; Ellie Grossman; Andrea Truncali; John Rotrosen; Andrew Rosenblum; Steven Magura; Marc N. Gourevitch

2011-01-01

80

Buprenorphine use in pregnant opioid users: a critical review.  

PubMed

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

Soyka, Michael

2013-08-01

81

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

PubMed

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

2013-01-25

82

Emergency Department Visits Involving Buprenorphine.  

National Technical Information Service (NTIS)

Buprenorphine is a medication used to treat opioid addiction. A properly prescribed dose of buprenorphine can help opioid-addicted individuals to stop misusing opioids without experiencing withdrawal symptoms. Although buprenorphine is itself an opioid, a...

2013-01-01

83

Buprenorphine and naloxone interactions in opiate-dependent volunteers  

Microsoft Academic Search

Objective: Sublingual buprenorphine appears useful in the treatment of opiate dependence. A combination sublingual dose of buprenorphine and naloxone could have less potential for parenteral use by opiate-dependent individuals. To estimate the abuse potential of a combination formulation, we assessed the parenteral effects of a buprenorphine and naloxone combination in untreated heroin addicts.Methods: Eight healthy, opiate-dependent daily users of heroin

John Mendelson; Reese T. Jones; Isabella Fernandez; Susette Welm; Ann K. Melby; Matthew J. Baggott

1996-01-01

84

Comparative Effects of Vasectomy Surgery and Buprenorphine Treatment on Faecal Corticosterone Concentrations and Behaviour Assessed by Manual and Automated Analysis Methods in C57 and C3H Mice  

PubMed Central

Establishing effective cage-side pain assessment methods is essential if post-surgical pain is to be controlled effectively in laboratory animals. Changes to overall activity levels are the most common methods of assessment, but may not be the most appropriate for establishing the analgesic properties of drugs, especially in mice, due their high activity levels. Use of drugs that can affect activity (e.g. opioids) is also a problem. The relative merits of both manual and automated behaviour data collection methods was determined in two inbred mouse strains undergoing vasectomy following treatment with one of 2 buprenorphine dose rates. Body weights and the effects of surgery and buprenorphine on faecal corticosterone were also measured. Surgery caused abnormal behaviour and reduced activity levels, but high dose buprenorphine caused such large-scale increases in activity in controls that we could not establish analgesic effects in surgery groups. Only pain-specific behaviour scoring using the manual approach was effective in showing 0.05 mg/kg buprenorphine alleviated post-vasectomy pain. The C57 mice also responded better to buprenorphine than C3H mice, indicating they were either less painful, or more responsive to its analgesic effects. C3H mice were more susceptible to the confounding effects of buprenorphine irrespective of whether data were collected manually or via the automated approach. Faecal corticosterone levels, although variable, were higher in untreated surgery mice than in control groups, also indicating the presence of pain or distress. Pain-specific scoring was superior to activity monitoring for assessing the analgesic properties of buprenorphine in vasectomised mice. Buprenorphine (0.01 mg/kg), in these strains of male mice, for this procedure, provided inadequate analgesia and although 0.05 mg/kg was more effective, not completely so. The findings support the recommendation that analgesic dose rates should be adjusted in relation to the potential severity of the surgical procedure, the mouse strain, and the individual animals' response.

Wright-Williams, Sian; Flecknell, Paul A.; Roughan, Johnny V.

2013-01-01

85

Training HIV Physicians to Prescribe Buprenorphine for Opioid Dependence  

ERIC Educational Resources Information Center

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…

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

2006-01-01

86

Attitudes toward buprenorphine and methadone among opioid-dependent individuals  

PubMed Central

Attitudes and beliefs about drug abuse treatment have long been known to shape response to that treatment. Two major pharmacological alternatives are available for opioid dependence: methadone, which has been available for the past 40 years, and buprenorphine, a recently-introduced medication. This mixed methods study examined the attitudes of opioid-dependent individuals toward methadone and buprenorphine. A total of 195 participants (n = 140 who were enrolling in one of 6 Baltimore area methadone programs and n = 55 who were out-of-treatment) were administered the Attitudes toward Methadone and toward Buprenorphine Scales and a subset (n = 46) received an ethnographic interview. In-treatment group had significantly more positive attitudes toward methadone than did the out-of-treatment group (p < .001), while they did not differ in their attitudes toward buprenorphine. Both groups had significantly more positive attitudes toward buprenorphine than methadone. Addressing these attitudes may increase treatment entry and retention.

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

2009-01-01

87

Socio-demographic Profile and Help-seeking Behaviour of Buprenorphine Abusers in Singapore  

Microsoft Academic Search

Introduction: The US Food and Drug Administration (FDA) approved buprenorphine or Subutex for the treatment of opiate dependence in October 2002. Buprenorphine is a partial agonist of the mu-opioid receptor; although initial animal research suggested a low abuse potential for buprenorphine, it was subsequently shown to have an abuse potential similar to that of morphine or hydromorphone. The objectives of

Munidasa Winslow; Wei-Ling Ng; Subramaniam Mythily

88

Disaccharides in urine samples as markers of intravenous abuse of methadone and buprenorphine.  

PubMed

Methadone and buprenorphine are commonly used as oral substitutes in opiate maintenance programs to treat persons who are dependent on heroin. During these programs, patients are not allowed to continue using illicit drugs. Abstinence can easily be monitored by urine tests with immunochemical methods. It is well known that the intravenous abuse of heroin substitutes like methadone or buprenorphine has become common as well. The methadone-prescribing physician has no opportunity to check whether the opiate maintenance treatment patient takes his substitution medicines orally as intended or continues with his intravenous misuse now substituting the methadone instead of injecting heroin. In Germany, substitutes are available as liquids and tablets that contain carbohydrates as adjuvants. Sucrose is used to increase viscosity in liquids, while lactose is needed for pressing tablets (e.g., Methaddict® and Subutex®). In case of oral ingestion, disaccharides are broken down into monosaccharides by disaccharidases in the small intestine. These monosaccharides are absorbed into the blood stream by special monosaccharide transporters. Disaccharidases do not exist in blood, thus sucrose and lactose are not split if substitute medicines are injected intravenously. Our assumption, therefore, was that they are excreted unchanged in urine. We investigated a method for the detection of disaccharides in urine as markers of intravenous abuse of substitutes. Urine samples of 26 intravenous substitute abusers showed all positive results for lactose (76.9%) and/or sucrose (73.1%). The method is assumed to be useful to detect intravenous abuse of substitutes. PMID:24099717

Jungen, Hilke; Andresen-Streichert, Hilke; Müller, Alexander; Iwersen-Bergmann, Stefanie

2013-01-01

89

Rifampin, but not Rifabutin, May Produce Opiate Withdrawal in Buprenorphine-Maintained Patients*  

PubMed Central

Background This series of studies examines the pharmacokinetic/pharmacodynamic interactions between buprenorphine, an opioid partial agonist increasingly used in treatment of opioid dependence, and rifampin, a medication used as a first line treatment for tuberculosis; or rifabutin, an alternative antituberculosis medication. Methods Opioid-dependent individuals on stable doses of buprenorphine/naloxone underwent two, 24-hour blood sampling studies: 1. for buprenorphine pharmacokinetics and 2. following 15 days of rifampin 600 mg daily or rifabutin 300 mg daily for buprenorphine and rifampin or rifabutin pharmacokinetics. Results Rifampin administration produced significant reduction in plasma buprenorphine concentrations (70% reduction in mean area under the curve (AUC); p=<0·001) and onset of opiate withdrawal symptoms in 50% of participants (p=0·02). While rifabutin administration to buprenorphine-maintained subjects resulted in a significant decrease in buprenorphine plasma concentrations (35% decrease in AUC; p<0·001) no opiate withdrawal was seen. Compared with historical control data, buprenorphine had no significant effect on rifampin pharmacokinetics, but was associated with 22% lower rifabutin mean AUC (p=0·009), although rifabutin and its active metabolite concentrations remained in the therapeutic range. Conclusions Rifampin is a more potent inducer of buprenorphine metabolism than rifabutin with pharmacokinetic and pharmacodynamic adverse consequences. Those patients requiring rifampin treatment for tuberculosis and receiving buprenorphine therapy are likely to require an increase in buprenorphine dose to prevent withdrawal symptoms. Rifabutin administration was associated with decreases in buprenorphine plasma concentrations, but no clinically significant adverse events were observed.

McCance-Katz, Elinore F.; Moody, David E.; Prathikanti, Sudha; Friedland, Gerald; Rainey, Petrie M.

2011-01-01

90

Transdermal buprenorphine for the treatment of cancer pain: results from a multicenter, observational, post-marketing study in Spain (RELIEF study).  

PubMed

SUMMARY Aim:This study evaluated health outcomes in patients with cancer pain during treatment with transdermal buprenorphine, including quality of life, effectiveness, tolerability, and functional consequences for patients and their carers. Methods: In this 3-month, noncomparative, multicenter, observational study performed in a normal clinical practice setting in Spain, patients received transdermal buprenorphine 37, 52.5 or 70 µg/h, with patches changed every 96 h. The effect of transdermal buprenorphine on quality of life (primary study focus) was assessed using the Visual Analog Scale (VAS) component of the EuroQol 5 Dimensions™ (EQ-5D). In addition, pain (assessed using the Brief Pain Inventory - Short Form [BPI-SF] and VAS-pain), the impact of pain on patients and carers (assessed using the Beck Depression Inventory, sleep quality analysis, VAS-patient limitation, VAS-carer limitation and the Palliative Care Scale), patient's use of health resources, patient satisfaction, and tolerability, were evaluated. Results: Of 116 patients entering the study, 42 completed the 3-month study period. Five patients withdrew due to adverse events. The two main reasons for study discontinuation were nontreatment-related death (27.1%) and lost to follow-up (18.8%). The mean age was 62.9 years and the mean baseline duration of pain was 7.78 weeks. In the month prior to starting transdermal buprenorphine, 80% of patients had received at least one nonopioid analgesic medication; 21% had received an opioid analgesic (most commonly tramadol). The most common dose of transdermal buprenorphine used was 35 µg/h. The mean improvement from baseline in the EQ-5D VAS score among 65 patients with data was 15.20 ± 24.96 (p < 0.0001). EQ-5D descriptive parameters also improved during the study (not statistically significant). Mean improvements in BPI scores for worst pain (3.76) and average pain (3.03) were significant (p < 0.0001). The other measures of pain relief also supported transdermal buprenorphine as an effective analgesic. Sleep quality improved during the study. VAS scores (100 mm scale) for patient limitation and caregiver burden due to pain improved, with a significant mean change in VAS-carer limitation score (30.34; p < 0.0001). Adverse events were reported by ten (8.6%) patients, most commonly affecting the gastrointestinal system (vomiting [4.3% of patients], nausea [2.6%] and constipation [0.9%]). The majority of patients reported satisfaction with their analgesic treatment. Conclusions: In this observational study in normal clinical practice, transdermal buprenorphine provided effective pain relief and was generally well tolerated by patients with cancer pain. It also improved quality of life for patients and reduced caregiver burden. Considering the high number of study discontinuations (mainly due to nontreatment-related death and lost to follow-up), the results of this study need to be evaluated with caution. PMID:24645762

Camps, Carlos; Casinello, Javier; Virizuela, J Antonio; Escobar, Yolanda; Sanchez-Magro, Isabel; Stern, Andres

2011-11-01

91

Cost analysis of clinic and office-based treatment of opioid dependence: results with methadone and buprenorphine in clinically stable patients.  

PubMed

The cost of providing and receiving treatment for opioid dependence can determine its adoption. To compare the cost of clinic-based methadone (MC, n=23), office-based methadone (MO, n=21), and office-based buprenorphine (BO, n=34) we performed an analysis of treatment and patient costs over 6 months of maintenance in patients who had previously been stabilized for at least 1 year. We performed statistical comparisons using ANOVA and chi-square tests and performed a sensitivity analysis varying cost estimates and intensity of clinical contact. The cost of providing 1 month of treatment per patient was $147 (MC), $220 (MO) and $336 (BO) (p<0.001). Mean monthly medication cost was $93 (MC), $86 (MO) and $257 (BO) (p<0.001). The cost to patients was $92 (MC), $63 (MO) and $38 (BO) (p=0.102). Sensitivity analyses, varying cost estimates and clinical contact, result in total monthly costs of $117 to $183 (MC), $149 to $279 (MO), $292 to $499 (BO). Monthly patient costs were $84 to $133 (MC), $55 to $105 (MO) and $34 to $65 (BO). We conclude that providing clinic-based methadone is least expensive. The price of buprenorphine accounts for a major portion of the difference in costs. For patients, office-based treatment may be less expensive. PMID:18804923

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

2009-01-01

92

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

PubMed Central

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.

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

2012-01-01

93

A retrospective evaluation of patients switched from buprenorphine (subutex) to the buprenorphine/naloxone combination (suboxone)  

PubMed Central

Background In Finland, buprenorphine (Subutex) is the most abused opioid. In order to curb this problem, many treatment centres transferred ("forced transfer") their buprenorphine patients to the buprenorphine plus naloxone (Suboxone) combination product in late 2003. Methods Data from a retrospective study involving five different treatment centers, examining the effects of switching patients to Suboxone, were gathered from 64 opioid-dependent patients who had undergone the medication transfer. Results Most patients (90.6%) switched to Suboxone at the same dose of buprenorphine that they had been receiving as Subutex (average 22 mg). The majority of these patients (71.9%) were maintained at the same dose of Suboxone throughout the 4-week study period. During the first 4 weeks, 50% of the patients reported adverse events and at the four month time point, 26.6% reported adverse events. However, due to adverse events one patient only discontinued treatment with Suboxone during the 4-week study period, and five during the four month follow-up period. Of the 26 patients in the follow-up period, Suboxone was misused intravenously once each by 4 patients and twice by 1 patient. These 5 patients all reported that injecting Suboxone was like injecting "nothing" with any euphoria, or that it was a bad experience. Conclusion We conclude that when patients are transferred from high doses (> 22 mg) of buprenorphine to the combination product, dose adjustments may be necessary especially in the later phase of the treatment. We recommend that a transfer from Subutex to Suboxone should be carefully discussed and planned in advance with the patients and after the transfer adverse events should be regularly monitored. With regard of buprenorphine IV abuse, the combination product seems to have a less abuse potential than buprenorphine alone.

Simojoki, Kaarlo; Vorma, Helena; Alho, Hannu

2008-01-01

94

Home Buprenorphine/Naloxone Induction in Primary Care  

PubMed Central

ABSTRACT BACKGROUND Buprenorphine can be used for the treatment of opioid dependence in primary care settings. National guidelines recommend directly observed initial dosing followed by multiple in-clinic visits during the induction week. We offered buprenorphine treatment at a public hospital primary care clinic using a home, unobserved induction protocol. METHODS Participants were opioid-dependent adults eligible for office-based buprenorphine treatment. The initial physician visit included assessment, education, induction telephone support instructions, an illustrated home induction pamphlet, and a 1-week buprenorphine/naloxone prescription. Patients initiated dosing off-site at a later time. Follow-up with urine toxicology testing occurred at day 7 and thereafter at varying intervals. Primary outcomes were treatment status at week 1 and induction-related events: severe precipitated withdrawal, other buprenorphine-prompted withdrawal symptoms, prolonged unrelieved withdrawal, and serious adverse events (SAEs). RESULTS Patients (N?=?103) were predominantly heroin users (68%), but also prescription opioid misusers (18%) and methadone maintenance patients (14%). At the end of week 1, 73% were retained, 17% provided induction data but did not return to the clinic, and 11% were lost to follow-up with no induction data available. No cases of severe precipitated withdrawal and no SAEs were observed. Five cases (5%) of mild-to-moderate buprenorphine-prompted withdrawal and eight cases of prolonged unrelieved withdrawal symptoms (8% overall, 21% of methadone-to-buprenorphine inductions) were reported. Buprenorphine-prompted withdrawal and prolonged unrelieved withdrawal symptoms were not associated with treatment status at week 1. CONCLUSIONS Home buprenorphine induction was feasible and appeared safe. Induction complications occurred at expected rates and were not associated with short-term treatment drop-out. Electronic supplementary material The online version of this article (doi:10.1007/s11606-008-0866-8) contains supplementary material, which is available to authorized users.

Grossman, Ellie; DiRocco, Danae; Gourevitch, Marc N.

2008-01-01

95

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

PubMed

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

Canestrelli, Corinne; Marie, Nicolas; Noble, Florence

2014-09-01

96

From research to the real world: Buprenorphine in the decade of the Clinical Trials Network  

Microsoft Academic Search

The National Institute on Drug Abuse (NIDA) established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to bring researchers and treatment providers together to develop a clinically relevant research agenda. Initial CTN efforts addressed the use of buprenorphine, a mu-opioid partial agonist, as treatment for opioid dependence. Strong evidence of buprenorphine's therapeutic efficacy was demonstrated in clinical

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

2010-01-01

97

Buprenorphine and methadone maintenance in jail and post-release: a randomized clinical trial.  

PubMed

Buprenorphine has rarely been administered as an opioid agonist maintenance therapy in a correctional setting. This study introduced buprenorphine maintenance in a large urban jail, Rikers Island in New York City. Heroin-dependent men not enrolled in community methadone treatment and sentenced to 10-90 days in jail (N=116) were voluntarily randomly assigned either to buprenorphine or methadone maintenance, the latter being the standard of care for eligible inmates at Rikers. Buprenorphine and methadone maintenance completion rates in jail were equally high, but the buprenorphine group reported for their designated post-release treatment in the community significantly more often than did the methadone group (48% vs. 14%, p<.001). Consistent with this result, prior to release from Rikers, buprenorphine patients stated an intention to continue treatment after release more often than did methadone patients (93% vs. 44%, p<.001). Buprenorphine patients were also less likely than methadone patients to withdraw voluntarily from medication while in jail (3% vs. 16%, p<.05). There were no post-release differences between the buprenorphine and methadone groups in self-reported relapse to illicit opioid use, self-reported re-arrests, self-reported severity of crime or re-incarceration in jail. After initiating opioid agonist treatment in jail, continuing buprenorphine maintenance in the community appears to be more acceptable to offenders than continuing methadone maintenance. PMID:18930603

Magura, Stephen; Lee, Joshua D; Hershberger, Jason; Joseph, Herman; Marsch, Lisa; Shropshire, Carol; Rosenblum, Andrew

2009-01-01

98

Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine  

Microsoft Academic Search

Buprenorphine and naloxone sublingual (s.l.) dose formulations may decrease parenteral buprenorphine abuse. We evaluated pharmacologic interactions between 8 mg s.l. buprenorphine combined with 0, 4, or 8 mg of naloxone in nine opiate-dependent volunteers stabilized on 8 mg s.l. buprenorphine for 7 days. Combined naloxone and buprenorphine did not diminish buprenorphine's effects on opiate withdrawal nor alter buprenorphine bioavailability. Opiate

Debra S Harris; Reese T Jones; Susette Welm; Robert A Upton; Emil Lin; John Mendelson

2000-01-01

99

Models for Integrating Buprenorphine Therapy into the Primary HIV Care Setting  

Microsoft Academic Search

Opiate dependence among human immunodeficiency virus (HIV)-infected patients has been associated with negative clinical outcomes, yet few affected patients receive appropriate and coordinated treatment for both conditions. The introduction of buprenorphine maintenance therapy into HIV care settings provides an opportunity for providers to integrate treatment for opiate dependence into their practices. Buprenorphine maintenance therapy has been associated with reductions in

Sanjay Basu; R. Douglas Bruce; Frederick L. Altice

2006-01-01

100

Interactions Between Buprenorphine and the Protease Inhibitors Darunavir-Ritonavir and Fosamprenavir-Ritonavir  

PubMed Central

Background.?This study examined drug interactions between buprenorphine, a partial opioid agonist used for opioid dependence treatment and pain management, and the protease inhibitors (PIs) darunavir-ritonavir and fosamprenavir-ritonavir. Methods.?The pharmacokinetics of buprenorphine and its metabolites and symptoms of opioid withdrawal or excess were compared in opioid-dependent, buprenorphine-naloxone–maintained, human immunodeficiency virus (HIV)–negative volunteers (11 for darunavir-ritonavir and 10 for fosamprenavir-ritonavir) before and after 15 days of PI administration. PI pharmacokinetics and adverse effects were compared between the buprenorphine-maintained participants and an equal number of sex-, age-, race-, and weight-matched, healthy, non–opioid-dependent volunteers who received darunavir-ritonavir or fosamprenavir-ritonavir but not buprenorphine. Results.?There were no significant changes in buprenorphine or PI plasma levels and no significant changes in medication adverse effects or opioid withdrawal. Increased concentrations of the inactive metabolite buprenorphine-3-glucuronide suggested that darunavir-ritonavir and fosamprenavir-ritonavir induced glucuronidation of buprenorphine. Conclusions.?Dose adjustments are not likely to be necessary when buprenorphine and darunavir-ritonavir or fosamprenavir-ritonavir are coadministered for the treatment of opioid dependence and HIV disease.

Rainey, Petrie M.; Moody, David E.; Morse, Gene D.; Ma, Qing; Prathikanti, Sudha; Pade, Patricia A.; Alvanzo, Anika A. H.; McCance-Katz, Elinore F.

2012-01-01

101

A review of the studies using buprenorphine in cats.  

PubMed

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

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

2014-05-01

102

Managing Opioid Addiction with Buprenorphine  

Microsoft Academic Search

Legislation has enabled physicians to treat opioid-dependent patients with an office-based main- tenance program using buprenorphine, a partial mu-opioid receptor agonist. Clinical studies indicate buprenorphine effectively manages opioid addiction. Buprenorphine is more effective than placebo for managing opioid addiction but may not be superior to methadone if high doses are needed. It is comparable to lower doses of methadone, however.

PAUL A. DONAHER; CHRISTOPHER WELSH

103

Effectiveness of buprenorphine in double diagnosed patients. Buprenorphine as psychothropic drug  

Microsoft Academic Search

Summary Opiate drugs were first proposed for the treatment of dysphoric syndromes, depression and psychoses many years ago. Even so, the usefulness of these compounds in psychiatry is supported by only a small corpus of data. The reasons given for the restrictions placed on opiate use are based on prejudice rather than scientific evidence. Buprenorphine, with its unique pharmacological profile,

Icro Maremmani; Matteo Pacini; Pier Paolo Pani

104

Buprenorphine and Norbuprenorphine in Hair of Pregnant Women and Their Infants after Controlled Buprenorphine Administration  

Microsoft Academic Search

Background: Buprenorphine is under investigation as a pharmacotherapeutic agent for treating opioid depen- dence in pregnant women. We hypothesized that there would be a relationship between the cumulative mater- nal dose of buprenorphine during pregnancy and the concentration of buprenorphine and norbuprenorphine in maternal and infant hair. Methods: This study examined buprenorphine and nor- buprenorphine concentrations in hair obtained from

Robert S. Goodwin; Diana G. Wilkins; Olga Averin; Robin E. Choo; Jennifer R. Schroeder; Donald R. Jasinski; Rolley E. Johnson; Hendree E. Jones; Marilyn A. Huestis

2007-01-01

105

Substituted phenylindoles for the treatment of HIV  

US Patent & Trademark Office Database

This invention is in the area of phenylindoles that are useful for the treatment of HIV infection, and, in particular, phenylindoles that exhibit significant activity against resistant strains of HIV. The phenylindoles have at least two substituents other than hydrogen on the benzo ring of the indole function, preferably at the 4' and 5', 5' and 6' or the 5' and 7' positions, optionally in combination with disubstitution at positions 3'' and 5'' on the phenyl ring of the compound, and carboxamide containing moieties at position-2 on the indole group of the compound. Methyl is a preferred group for substitution on the phenyl ring. Preferred substituents for the benzo ring of the indole function include but are not limited to chlorine, fluorine, bromine, iodine, CF.sub.3, methoxy, CN, and NO.sub.2.

2008-04-29

106

From Research to the Real World: Buprenorphine in the Decade of the Clinical Trials Network  

PubMed Central

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

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

2010-01-01

107

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

PubMed

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

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

2012-07-01

108

Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. A Treatment Improvement Protocol TIP 40.  

National Technical Information Service (NTIS)

This Treatment Improvement Protocol (TIP) is composed of 6 chapters and 10 appendices, including a complete list of references (Appendix A, Bibliography). Chapter 1, Introduction, describes the basic facts regarding opioid addiction, the traditional appro...

2004-01-01

109

Buprenorphine-Naloxone Maintenance Following Release from Jail  

PubMed Central

Primary care is understudied as a re-entry drug and alcohol treatment setting. This study compared treatment retention and opioid misuse among opioid dependent adults seeking buprenorphine/naloxone maintenance in an urban primary care clinic following release from jail vs. community referrals. Post-release patients were either; a) induced to buprenorphine in-jail as part of a clinical trial, or, b) seeking buprenorphine induction post-release. From 2007–2008, N=142 patients were new to primary care buprenorphine: n=32 post-release; n=110 induced after community referral and without recent incarceration. Jail-released patients were more likely African American or Hispanic and uninsured. Treatment retention rates for post-release (37%) vs. community (30%) referrals were similar at 48 weeks. Rates of opioid positive urines and self-reported opioid misuse were also similar between groups. Post-release patients in primary care buprenorphine treatment had equal treatment retention and rates of opioid abstinence vs. community-referred patients.

Lee, Joshua D.; Grossman, Ellie; Truncali, Andrea; Rotrosen, John; Rosenblum, Andrew; Magura, Steven; Gourevitch, Marc N.

2012-01-01

110

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

PubMed Central

Background Having opioid dependence and HIV infection are associated with poor HIV-related treatment outcomes. Methods HIV-infected, opioid-dependent subjects (N = 295) recruited from 10 clinical sites initiated buprenorphine/naloxone (BUP/NX) and were assessed at baseline and quarterly for 12 months. Primary outcomes included receiving antiretroviral therapy (ART), HIV-1 RNA suppression, and mean changes in CD4 lymphocyte count. Analyses were stratified for the 119 subjects not on ART at baseline. Generalized estimating equations were deployed to examine time-dependent correlates for each outcome. Results At baseline, subjects on ART (N = 176) were more likely than those not on ART (N = 119) to be older, heterosexual, have lower alcohol addiction severity scores, and lower HIV-1 RNA levels; they were less likely to be homeless and report sexual risk behaviors. Subjects initiating BUP/NX (N = 295) were significantly more likely to initiate or remain on ART and improve CD4 counts over time compared with baseline; however, these improvements were not significantly improved by longer retention on BUP/NX. Retention on BUP/NX for three or more quarters was, however, significantly associated with increased likelihood of initiating ART (? = 1.34 [1.18, 1.53]) and achieve viral suppression (? = 1.25 [1.10, 1.42]) for the 64 of 119 (54%) subjects not on ART at baseline compared with the 55 subjects not retained on BUP/NX. In longitudinal analyses, being on ART was positively associated with increasing time of observation from baseline and higher mental health quality of life scores (? = 1.25 [1.06, 1.46]) and negatively associated with being homo- or bisexual (? = 0.55 [0.35, 0.97]), homeless (? = 0.58 [0.34, 0.98]), and increasing levels of alcohol addiction severity (? = 0.17 [0.03, 0.88]). The strongest correlate of achieving viral suppression was being on ART (? = 10.27 [5.79, 18.23]). Female gender (? = 1.91 [1.07, 3.41]), Hispanic ethnicity (? = 2.82 [1.44, 5.49]), and increased general health quality of life (? = 1.02 [1.00,1.04]) were also independently correlated with viral suppression. Improvements in CD4 lymphocyte count were significantly associated with being on ART and increased over time. Conclusions Initiating BUP/NX in HIV clinical care settings is feasible and correlated with initiation of ART and improved CD4 lymphocyte counts. Longer retention on BPN/NX was not associated with improved prescription of ART, viral suppression, or CD4 lymphocyte counts for the overall sample in which the majority was already prescribed ART at baseline. Among those retained on BUP/NX, HIV treatment outcomes did not worsen and were sustained. Increasing time on BUP/NX, however, was especially important for improving HIV treatment outcomes for those not on ART at baseline, the group at highest risk for clinical deterioration. Retaining subjects on BUP/NX is an important goal for sustaining HIV treatment outcomes for those on ART and improving them for those who are not. Comorbid substance use disorders (especially alcohol), mental health problems, and quality–of-life indicators independently contributed to HIV treatment outcomes among HIV-infected persons with opioid dependence, suggesting the need for multidisciplinary treatment strategies for this population.

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

2012-01-01

111

Network therapy: decreased secondary opioid use during buprenorphine maintenance.  

PubMed

Network therapy (NT) employs family members and/or friends to support compliance with an addiction treatment carried out in office practice. This study was designed to ascertain whether NT is a useful psychosocial adjunct, relative to a control treatment, for achieving diminished illicit heroin use for patients on buprenorphine maintenance. Patients agreeing to randomization to either NT (N = 33) or medication management (MM, N = 33) were inducted onto short-term buprenorphine maintenance and then tapered to zero dose. NT resulted in significantly more urine toxicologies negative for opioids than MM (65% vs. 45%) and more NT than MM patients (50% vs. 23%) experienced a positive outcome relative to secondary heroin use by the end of treatment. The use of NT in office practice may therefore improve the effectiveness of eliminating secondary heroin use during buprenorphine maintenance. It may also be useful in enhancing compliance with an addiction treatment regimen in other contexts. PMID:15182896

Galanter, Marc; Dermatis, Helen; Glickman, Linda; Maslansky, Robert; Sellers, M Brealyn; Neumann, Erna; Rahman-Dujarric, Claudia

2004-06-01

112

Buprenorphine and naloxone combinations: the effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers  

Microsoft Academic Search

Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for\\u000a parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The\\u000a effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms\\u000a were examined in 12 opiate-dependent subjects. Following stabilization

J. Mendelson; Reese T. Jones; Susette Welm; Matthew Baggott; Isabella Fernandez; Ann K. Melby; Rajneesh P. Nath

1999-01-01

113

A novel community-based buprenorphine program: client description and initial outcomes.  

PubMed

The aims of this retrospective, descriptive study were to describe clients served by a buprenorphine program in a community-based recovery center and to present initial treatment outcomes. A record review was conducted for clients treated from July 2010 to August 2011. Client demographic, health, substance use, and treatment history data were abstracted from the records of the first 78 clients served. Buprenorphine and opiate use data were collected via urine toxicology reports, collected weekly among clients who remained enrolled in treatment. The average percentages of weeks spent opiate free and buprenorphine compliant were 83% (SD = 26%) and 95% (SD = 13%), respectively. When positive heroin toxicology and negative buprenorphine toxicology were replaced for the missing/unknown data, the average percentages of opiate-abstinent weeks and buprenorphine compliance were 60% (SD = 34%) and 74% (SD = 28%), respectively. Roughly half of all clients (49%) were successfully transitioned to continue treatment with buprenorphine in a primary care setting. Findings from this study demonstrate that buprenorphine treatment for opiate dependence can be incorporated into a community-based recovery center with high rates of opiate abstinence and treatment adherence. PMID:24394496

Daniels, Amy M; Salisbury-Afshar, Elizabeth; Hoffberg, Adam; Agus, Deborah; Fingerhood, Michael I

2014-01-01

114

Network therapy: Decreased secondary opioid use during buprenorphine maintenance  

Microsoft Academic Search

Network therapy (NT) employs family members and\\/or friends to support compliance with an addiction treatment carried out in office practice. This study was designed to ascertain whether NT is a useful psychosocial adjunct, relative to a control treatment, for achieving diminished illicit heroin use for patients on buprenorphine maintenance. Patients agreeing to randomization to either NT (N = 33) or

Marc Galanter; Helen Dermatis; Linda Glickman; Robert Maslansky; M. Brealyn Sellers; Erna Neumann; Claudia Rahman-Dujarric

2004-01-01

115

The Implementation of Buprenorphine/Naloxone in College Health Practice  

ERIC Educational Resources Information Center

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…

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

2008-01-01

116

Sublingual versus subcutaneous buprenorphine in opiate abusers  

Microsoft Academic Search

To compare the pharmacologic profiles of sublingually and subcutaneously administered buprenorphine, 10 healthy male subjects with histories of opiate abuse were given sublingually administered buprenorphine (1, 2, and 4 mg), subcutaneously administered buprenorphine (1 and 2 mg), and placebo in a double-blind, double-dummy, placebo-controlled study. All active buprenorphine dosages produced a significant degree of miosis but no significant changes in

Donald R Jasinski; Paul J Fudala; Rolley E Johnson; R E Johnson NIDA

1989-01-01

117

Buprenorphine as a Pharmacotherapy for Cocaine Abuse  

Microsoft Academic Search

The partial µ-opiate agonist, buprenorphine, is the subject of recent evaluation as a potential pharmacotherapy for cocaine dependence. This paper reviews the extant preclinical and clinical evidence of buprenorphine effectiveness in treating cocaine abuse, including data from our large methadone comparison trial and a smaller buprenorphine dose ranging study. Although buprenorphine appears to reduce cocaine self-administration in studies of non-opiate

Peggy A. Compton; Walter Ling; V. Charles Charuvastra; Donald R. Wesson

1995-01-01

118

Evaluation on drug dependence of buprenorphine 1  

Microsoft Academic Search

AIM: To survey and assess the drug dependence and abuse potential liability of buprenorphine among opiate abusers. METHODS: Subjects of opiate dependence with history of buprenorphine use for 3 d at least were surveyed by interview. Physical dependence of buprenorphine was assessed using 30 items opiate withdrawal scale (OWS), which composed of 30 symptoms\\/signs. A 4-point scale was used to

LIU Zhi-Min; LÜ Xian-Xiang; LIAN Zhi; GUO Ping; AN Xin

119

Buprenorphine TDS: use in daily practice, benefits for patients.  

PubMed

In Germany and many other countries, buprenorphine has been used for a long time for the management of pain in both cancer and non-cancer patients. Although a transdermal delivery system for buprenorphine (Transtec) has recently been introduced, the clinical experience in daily practice with this drug, delivered in a matrix patch, is only now being evaluated. In preliminary data from a survey of 3,255 patients with chronic pain, 26% had cancer pain, while the most common diagnoses of the other respondents included back pain (33%), osteoarthritis (22%), osteoporosis (17%), and neuropathic pain (10%, multiple entries). Before being switched to the buprenorphine patch, most patients had been pretreated with World Health Organization (WHO) Step II opioids (47%) or WHO Step III opioids (18%), including tramadol (in 35% of patients) and a tilidin/naloxone combination (15%); 9% had not been prescribed any opioids in advance of receiving transdermal buprenorphine. Most patients (77%) in the survey had been started on the lowest dose of the buprenorphine patch (35 microg/h), and nearly half (49%) were placed on adjuvant analgesics, including tramadol or tilidin/naloxone. Pain relief was rated as good or very good by 81% of the respondents. Adverse effects were similar to those seen on other opioids, although their intensity was mild in most cases. Local side effects, including erythema (4% of cases) and pruritus (1%), were transitory. Based on the survey results, transdermal buprenorphine is considered an effective opioid treatment for patients with stable cancer and non-cancer pain; it may prove particularly useful in patients who have experienced side effects taking oral analgesic preparations, as well as in those who are taking extensive co-medications. PMID:12665120

Radbruch, Lukas

2003-02-01

120

Buprenorphine Suppresses Cocaine Self-Administration by Rhesus Monkeys  

Microsoft Academic Search

Cocaine abuse has reached epidemic proportions in the United States, and the search for an effective pharmacotherapy continues. Because primates self-administer most of the drugs abused by humans, they can be used to predict the abuse liability of new drugs and for preclinical evaluation of new pharmacotherapies for drug abuse treatment. Daily administration of buprenorphine (an opioid mixed agonist-antagonist) significantly

Nancy K. Mello; Jack H. Mendelson; Mark P. Bree; Scott E. Lukas

1989-01-01

121

Opioid Abstinence Reinforcement Delays Heroin Lapse during Buprenorphine Dose Tapering  

ERIC Educational Resources Information Center

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…

Greenwald, Mark K.

2008-01-01

122

Open-label trial of an injection depot formulation of buprenorphine in opioid detoxification  

Microsoft Academic Search

Buprenorphine, a partial mu-opioid agonist, has been shown effective for treatment of opioid dependence but also has some abuse potential. A novel formulation of buprenorphine, using a polymer microcapsule depot sustained-release technology, has been developed which may offer effective treatment of opioid dependence while also minimizing risks of patient noncompliance and illicit diversion. This open-label, first-in-human study evaluated the safety

Bai-Fang X. Sobel; Stacey C. Sigmon; Sharon L. Walsh; Rolley E. Johnson; Ira A. Liebson; Elie S. Nuwayser; James H. Kerrigan; George E. Bigelow

2004-01-01

123

Opioid Addiction and Pregnancy: Perinatal Exposure to Buprenorphine Affects Myelination in the Developing Brain  

PubMed Central

Buprenorphine is a ?-opioid receptor partial agonist and ?-opioid receptor antagonist currently on trials for the management of pregnant opioid-dependent addicts. However, little is known about the effects of buprenorphine on brain development. Oligodendrocytes express opioid receptors in a developmentally regulated manner and thus, it is logical to hypothesize that perinatal exposure to buprenorphine could affect myelination. To investigate this possibility, pregnant rats were implanted with minipumps to deliver buprenorphine at 0.3 or 1 mg/kg/day. Analysis of their pups at different postnatal ages indicated that exposure to 0.3 mg/kg/day buprenorphine caused an accelerated and significant increase in the brain expression of all myelin basic protein (MBP) splicing isoforms. In contrast, treatment with the higher dose caused a developmental delay in MBP expression. Examination of corpus callosum at 26-days of age indicated that both buprenorphine doses cause a significant increase in the caliber of the myelinated axons. Surprisingly, these axons have a disproportionately thinner myelin sheath, suggesting alterations at the level of axon-glial interactions. Analysis of myelin associated glycoprotein (MAG) expression and glycosylation indicated that this molecule may play a crucial role in mediating these effects. Co-immunoprecipitation studies also suggested a mechanism involving a MAG-dependent activation of the Src-family tyrosine kinase Fyn. These results support the idea that opioid signaling plays an important role in regulating myelination in vivo and stress the need for further studies investigating potential effects of perinatal buprenorphine exposure on brain development.

SANCHEZ, EMILSE S.; BIGBEE, JOHN W.; FOBBS, WAMBURA; ROBINSON, SUSAN E.; SATO-BIGBEE, CARMEN

2008-01-01

124

Urine specimen detection of concurrent nonprescribed medicinal and illicit drug use in patients prescribed buprenorphine.  

PubMed

Patients being treated with buprenorphine usually have a history of opioid dependence and may be predisposed to misuse of drugs. Concurrent drug misuse increases the risk of life-threatening drug interactions. This retrospective data analysis observed which nonprescribed and illicit drugs were most commonly detected in the urine of patients from pain management clinics taking buprenorphine with or without a prescription. GC, LC/MS and LC-MS-MS were used to quantify 20,929 urine specimens. The most prevalent illicit drug used in both the groups (prescribed and nonprescribed buprenorphine) was marijuana, followed by cocaine. The most prevalent nonprescribed medications abused by both the groups were benzodiazepines, followed by oxycodone and hydrocodone. The overall prevalence of illicit and nonprescribed drug use was significantly higher in subjects who used buprenorphine without a prescription versus prescribed use. Of the concurrent use of marijuana and cocaine with buprenorphine, cocaine is most concerning since it decreases exposure to buprenorphine (lower area under the concentration-time curve and maximum concentration). The concurrent use of nonprescribed benzodiazepines with buprenorphine can cause excess sedation leading to respiratory depression and even death. These findings highlight the importance of educating patients about these potential toxicities. Furthermore, pain providers should consider expanding the spectrum of drugs that they monitor in patients under treatment. PMID:24080973

Guo, Alexander Y; Ma, Joseph D; Best, Brookie M; Atayee, Rabia S

2013-01-01

125

Utilizing buprenorphine-naloxone to treat illicit and prescription-opioid dependence  

PubMed Central

Objectives To review current evidence on buprenorphine–naloxone (bup/nx) for the treatment of opioid-use disorders, with a focus on strategies for clinical management and office-based patient care. Quality of evidence Medline and the Cochrane Database of Systematic Reviews were searched. Consensus reports, guidelines published, and other authoritative sources were also included in this review. Apart from expert guidelines, data included in this review constitute level 1 evidence. Findings Bup/nx is a partial ?-opioid agonist combined with the opioid antagonist naloxone in a 4:1 ratio. It has a lower abuse potential, carries less stigma, and allows for more flexibility than methadone. Bup/nx is indicated for both inpatient and ambulatory medically assisted withdrawal (acute detoxification) and long-term substitution treatment (maintenance) of patients who have a mild-to-moderate physical dependence. A stepwise long-term substitution treatment with regular monitoring and follow-up assessment is usually preferred, as it has better outcomes in reducing illicit opioid use, minimizing concomitant risks such as human immunodeficiency virus and hepatitis C transmission, retaining patients in treatment and improving global functioning. Conclusion Bup/nx is safe and effective for opioid detoxification and substitution treatment. Its unique pharmaceutical properties make it particularly suitable for office-based maintenance treatment of opioid-use disorder.

Mauger, Sofie; Fraser, Ronald; Gill, Kathryn

2014-01-01

126

A randomized trial of buprenorphine maintenance for heroin dependence in a primary care clinic for substance users versus a methadone clinic  

Microsoft Academic Search

PURPOSE: Buprenorphine is an alternative to methadone for the maintenance treatment of heroine dependence and may be effective on a thrice weekly basis. Our objective was to evaluate the effect of thrice weekly buprenorphine maintenance for the treatment of heroin dependence in a primary care clinic on retention in treatment and illicit opioid use.SUBJECTS AND METHODS: Opioid-dependent patients were randomly

PatrickG O’Connor; AlisonH Oliveto; JuliaM Shi; ElisaG Triffleman; KathleenM Carroll; ThomasR Kosten; BruceJ Rounsaville; JulianaA Pakes; RichardS Schottenfeld

1998-01-01

127

Substitution treatment for opioid addicts in Germany  

Microsoft Academic Search

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

Ingo Ilja Michels; Heino Stöver; Ralf Gerlach

2007-01-01

128

The cost-effectiveness of buprenorphine maintenance therapy for opiate addiction in the United States  

Microsoft Academic Search

Aims. To determine the cost-effectiveness of buprenorphine maintenance therapy for opiate addiction in the United States, particularly its effect on the HIV epidemic. Design. We developed a dynamic model to capture the effects of adding buprenorphine maintenance to the current opiate dependence treatment system. We evaluated incremental costs, including all health-care costs, and incremental effectiveness, measured as quality-adjusted life years

Paul G. Barnett; Gregory S. Zaric; Margaret L. Brandeau

2001-01-01

129

Benzodiazepine use among opiate-dependent subjects in buprenorphine maintenance treatment: Correlates of use, abuse and dependence  

Microsoft Academic Search

BackgroundPrevious studies from North America, Europe and Australia have reported high levels of benzodiazepine use among opiate-dependent patients in opiate maintenance treatment. However, to date, there are no available data on patterns of abuse and dependence on benzodiazepines according to DSM criteria among these patients.

Estelle Lavie; Mélina Fatséas; Cécile Denis; Marc Auriacombe

2009-01-01

130

Short-Term Buprenorphine Maintenance  

Microsoft Academic Search

Fifty-two heroin addicts were inducted onto buprenorphine under the care of psychiatric residents in a setting modeled on office practice. Subjects were maintained on a protocol of six weeks of 16 mg daily dosing, then tapered to zero dose up to week 16, and maintained on placebo through week 18. Of 44 subjects who continued after the first induction dose,

Marc Galanter; Helen Dermatis; Richard Resnick; Robert Maslansky; Erna Neumann

2003-01-01

131

[Possibilities and limits of drug substitution treatment in ambulatory practice].  

PubMed

The controversial discussion about the use of methadone in the treatment of drug addicts has occupied specialists in West Germany for decades. Owing to the political pressure to find a solution to the drug problem, methadone has been an established place in the classical drug treatment system for a long time. Therefore, there has been a supplement (in 1991) to the guidelines of the N.U.B. that under special conditions, it is now possible, for a physician working in a practice or outpatient clinic to use methadone substitution as a routine procedure. The psychosocial care of the patient ist also very important in addition to the purely medical provision of a substitute drug which blocks the heroin hunger and helps prevent criminal activity. The profound dependence of a drug addict is not created primarily by the consumption of addictive substances but must be seen as the result of a severely disturbed personality development and treated accordingly. The individual context of the particular drug scene, scene behavior and jargon should also be taken into account. It is not sufficient to explain addiction and dependence by means of chemical formula or physiological processes. Thus, a substitution treatment always includes two crucial aspects: the soothing and protecting aspect of the medicine administered and the conflict and insight orientated aspect of the therapeutic commitment. The physician, the clinic employees and the social worker should be comprehensively and thoroughly qualified in order to deal with the equally wide-ranging demands of substitutions therapy. PMID:8928530

Siegel, I

1996-06-01

132

Electrically-assisted transdermal delivery of buprenorphine  

Microsoft Academic Search

The objective of this study was to explore the electrically assisted transdermal delivery of buprenorphine. Oral delivery of buprenorphine, a synthetic opiate analgesic, is less efficient due to low absorption and large first-pass metabolism. While transdermal delivery of buprenorphine is expected to avoid the first-pass effect and thereby be more bioavailable, use of electrical enhancement techniques (iontophoresis and\\/or electroporation) could

Sagarika Bose; William R. Ravis; Yuh-Jing Lin; Lei Zhang; Günter A. Hofmann; Ajay K. Banga

2001-01-01

133

The Wellbeing of Infants Exposed to Buprenorphine via Breast Milk at 4 Weeks of Age.  

PubMed

Background: Buprenorphine has been available in Australia since 2000 as an alternative pharmacotherapy to methadone for the treatment of opioid dependence. However, there is little information in the literature regarding the effect of buprenorphine on the wellbeing of infants exposed to buprenorphine via breast milk, following discharge from hospital. Objective: The aim of the present study was to examine the wellbeing of infants exposed to buprenorphine via breast milk up to 4 weeks postnatally. Methods: Approximately 4 weeks after birth, information on the feeding and sleeping patterns, skin color, infant elimination patterns and hydration, and Neonatal Abstinence Scores of infants (n = 7) exposed to buprenorphine via breast milk was collected via both observation and documentation. Results: Infants were progressing well, with normal sleep patterns and skin color, and 2 mothers had minor concerns regarding infant elimination patterns. Four infants were exclusively breastfed and 3 were receiving a supplement, with a range of 260 to 700 mL of formula over 24 hours. The sleep patterns following feeding ranged from 1.55 to 3.33 hours, with a median of 2.12 hours. Conclusion: No adverse effects were detected in infants exposed to buprenorphine via breast milk up to 4 weeks postnatally. Further research using larger samples to assess possible developmental effects over longer periods of time is required. PMID:24399105

Gower, Shelley; Bartu, Anne; Ilett, Kenneth F; Doherty, Dorota; McLaurin, Renate; Hamilton, Dale

2014-05-01

134

Randomized, placebo-controlled pilot trial of gabapentin during an outpatient, buprenorphine-assisted detoxification procedure.  

PubMed

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-week, 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 and 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 years) 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 × Time interaction, such that the probability of opioid-positive urines significantly decreased over time in the gabapentin versus placebo groups during Weeks 3 and 4 (OR = 0.73, p = .004). These results suggest that gabapentin reduces opioid use during a 10-day buprenorphine detoxification procedure. PMID:23855333

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

2013-08-01

135

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

PubMed

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

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

2010-03-20

136

Factors that Affect the Efficacy of Buprenorphine and Naloxone as a Replacement Medication in Treating Opioid Dependence in the Primary Care Setting in Mendocino County, California  

Microsoft Academic Search

Introduction: Opioid dependence is a serious and growing public health issue. Treatment options have expanded since buprenorphine was approved for use as a maintenance medication by primary care providers in outpatient settings, but use of this medication is sti11limited. The safety and efficacy of buprenorphine have been well established, but very little is understood about what contributes to the success

Kelli Cole

2005-01-01

137

12 CFR 3.36 - Guarantees and credit derivatives: substitution treatment.  

...2014-01-01 2014-01-01 false Guarantees and credit derivatives: substitution treatment. 3...Approach Risk-Weighted Assets for General Credit Risk § 3.36 Guarantees and credit derivatives: substitution treatment....

2014-01-01

138

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

...2014-01-01 2014-01-01 false Guarantees and credit derivatives: substitution treatment. 217...Approach Risk-Weighted Assets for General Credit Risk § 217.36 Guarantees and credit derivatives: substitution treatment....

2014-01-01

139

12 CFR 324.36 - Guarantees and credit derivatives: Substitution treatment.  

...2014-01-01 2014-01-01 false Guarantees and credit derivatives: Substitution treatment. 324...Approach Risk-Weighted Assets for General Credit Risk § 324.36 Guarantees and credit derivatives: Substitution treatment....

2014-01-01

140

Buprenorphine and methadone for opioid addiction during pregnancy.  

PubMed

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. PMID:24845488

Mozurkewich, Ellen L; Rayburn, William F

2014-06-01

141

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

PubMed Central

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 ?-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.

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

2011-01-01

142

Correlations of maternal buprenorphine dose, buprenorphine, and metabolite concentrations in meconium with neonatal outcomes.  

PubMed

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS. PMID:18701886

Kacinko, S L; Jones, H E; Johnson, R E; Choo, R E; Huestis, M A

2008-11-01

143

Abuse and diversion of buprenorphine sublingual tablets and film.  

PubMed

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

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

144

Preliminary Study of Buprenorphine and Bupropion for Opioid Dependent Smokers  

PubMed Central

In this double-blind, placebo-controlled trial, bupropion (BUPRO, 300 mg/day) was compared to placebo (PBO) for concurrent treatment of opioid and tobacco addiction in 40 opioid-dependent smokers stabilized on buprenorphine (BUPRE, 24 mg/day). Participants received contingent, monetary reinforcement for abstinence from smoking, illicit opioids, and cocaine. Significant differences in treatment retention were observed (BUPRE+BUPRO, 58%; BUPRE+PBO, 90%). BUPRO treatment was not more effective than placebo for abstinence from tobacco, opioids, or cocaine in BUPRE stabilized patients. These preliminary findings do not support the efficacy of BUPRO, in combination with BUPRE, for concurrent treatment of opioid and tobacco addiction.

Mooney, Marc E.; Poling, James; Gonzalez, Gerardo; Gonsai, Kishor; Kosten, Thomas; Sofuoglu, Mehmet

2008-01-01

145

A preliminary study comparing methadone and buprenorphine in patients with chronic pain and coexistent opioid addiction.  

PubMed

Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge. Fifty-four participants with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up examination, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043), and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term, low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction. PMID:23480249

Neumann, Anne M; Blondell, Richard D; Jaanimägi, Urmo; Giambrone, Amanda K; Homish, Gregory G; Lozano, Jacqueline R; Kowalik, Urszula; Azadfard, Mohammadreza

2013-01-01

146

Self-management of buprenorphine/naloxone among online discussion board users.  

PubMed

Background: Buprenorphine/naloxone is an effective medication used to treat opioid dependence. Patients in treatment and those using it illegally without prescriptions have discussed using buprenorphine/naloxone anonymously on Internet discussion boards. Their beliefs about self-treatment and efforts to self-treat are not well known. Objectives: To identify facilitators of self-treatment by online buprenorphine/naloxone users. Methods: A qualitative, retrospective study of discussion board postings from September 2010 to November 2012 analyzed 121 threads from 13 discussion boards using grounded theory. Results: Facilitators of self-management themes that emerged included: (1) a ready supply of buprenorphine/naloxone from a variety of sources; (2) distrust of buprenorphine prescribers and pharmaceutical companies; (3) the declaration that buprenorphine/naloxone is a "bad-tasting" medicine; (4) the desire to adopt a different delivery method other than sublingually; and (5) a desire to become completely "substance-free." The sublingual film formulation appears to be an important facilitator in self-treatment because it can more easily be apportioned to extend the medication because of limited supply, cost, or to taper. Conclusions/Importance: The findings indicate a range of self-management activities ranging from altering the amount taken to modifying the physical medication composition or changing the administration route; some of these behaviors constitute problematic extra-medical use. Contributors to discussion boards seem to trust each other more than they trust pharmacists and prescribing physicians. The shared knowledge and behaviors of this understudied online community are important to healthcare providers because of the previously unknown precautions and risks taken to self-treat. PMID:24779501

Brown, Shan-Estelle; Altice, Frederick L

2014-07-01

147

Assessment of differential doses of buprenorphine for long term pharmacotherapy among opiate dependent subjects.  

PubMed

The aim of the present study was to evaluate, two different doses of sublingual buprenorphine (2 mg and 4 mg) among patients on maintenance treatment and to assess the relationship of steady state plasma level with craving. Twenty three male opioid dependent (ICD-10 DCR) subjects, were assigned to double blind randomized controlled trial of 2 and 4 mg/day doses of buprenorphine in an inpatient setting. They were evaluated thrice (2nd, 7th and 14th day) in 2 weeks for withdrawal symptoms (acute and protracted), sedation, euphoria, craving, side effects, global rating of well being and for measurement of plasma levels of buprenorphine. The data showed that there were no significant difference in scores of euphoria and sedation, protracted withdrawal symptoms and side effects, craving and overall well being and plasma level of buprenorphine among the subjects. However, both the groups had significant difference in score on almost all the measurements on final observation in comparison to initial observation. Both 2 mg/day and 4 mg/day dose of buprenorphine were effective in long term pharmacotherapy of opioid dependence without significant difference as compared by different measures used in the study. PMID:18831352

De, Shantanu; Jain, Raka; Ray, Rajat; Dhawan, Anju; Varghese, Sunny T

2008-01-01

148

Respiratory Rates and Arterial Blood-Gas Tensions in Healthy Rabbits Given Buprenorphine, Butorphanol, Midazolam, or Their Combinations  

PubMed Central

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 pO2. No significant changes in pCO2 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.

Schroeder, Carrie A; Smith, Lesley J

2011-01-01

149

Buprenorphine/Naloxone Reduces the Reinforcing and Subjective Effects of Heroin in Heroin-Dependent Volunteers  

PubMed Central

Rationale Although buprenorphine is effective in treating opioid dependence, optimal maintenance doses of buprenorphine or the buprenorphine/naloxone combination have not yet been established. Objective The present study was designed to evaluate the effects of buprenorphine/naloxone maintenance (2/0.5, 8/2, 32/8 mg sublingual) on the reinforcing and subjective effects of heroin (0, 12.5, 25, 50, and 100 mg intranasal) in heroin-dependent individuals. Methods During test weeks, participants (N=7) first sampled a dose of heroin and $20. During subsequent choice sessions, participants could choose to self administer heroin and/or money. Participants responded under a modified progressive-ratio schedule (PR 50, …, 2800) during a 10-trial self-administration task. Results Heroin break point values and subjective responses were significantly lower under 8/2 and 32/8 mg buprenorphine/naloxone compared to 2/0.5 mg. The self-administration and subjective effects data for heroin in the presence of buprenorphine/naloxone were compared to a separate control group of recently detoxified participants (N=8) in order to obtain estimates for the apparent in vivo dissociation constant (KA), the efficacy estimate (tau), and the estimated fraction of receptors remaining after buprenorphine/naloxone treatment (q). The apparent in vivo dissociation constant for heroin ranged from 50–126 mg (KA) and the efficacy estimate ranged from 13–20 (tau). In addition, 2/0.5, 8/2 and 32/8 mg buprenorphine/naloxone dose-dependently reduced the receptor population by 74%, 83%, and 91%, respectively. Conclusions These data demonstrate that both 8/2 and 32/8 mg buprenorphine/naloxone were well tolerated and effective in reducing the reinforcing and subjective effects of heroin, relative to the 2/0.5 mg dose. The data also show for the first time in humans that it is possible to quantify the efficacy and affinity of heroin for mu opioid receptors and that 80–90% of mu receptors need to be inactivated in order to obtain significant reductions in heroin-induced effects. These results have important implications for future studies in which it will be possible to obtain estimates of relative affinity and efficacy of different agonists at mu opioid receptors.

Comer, Sandra D.; Walker, Ellen A.; Collins, Eric D.

2013-01-01

150

Major bone defect treatment with an osteoconductive bone substitute.  

PubMed

A bone defect can be provoked by several pathological conditions (e.g. bone tumours, infections, major trauma with bone stock loss) or by surgical procedures, required for the appropriate treatment. Surgical techniques currently used for treating bone defects may count on different alternatives, including autologous vascularized bone grafts, homologous bone graft provided by musculoskeletal tissue bank, heterologous bone graft (xenograft), or prostheses, each one of them dealing with both specific advantages and complications and drawbacks. The main concerns related to these techniques respectively are: donor site morbidity and limited available amount; possible immune response and viral transmission; possible animal-derived pathogen transmission and risk of immunogenic rejection; high invasiveness and surgery-related systemic risks, long post-operative. physical recovery and prostheses revision need. Nowadays, an ideal alternative is the use of osteoconductive synthetic bone substitutes. Many synthetic substitutes are available, used either alone or in combination with other bone graft. Synthetic bone graft materials available as alternatives to autogeneous bone include calcium sulphates, special glass ceramics (bioactive glasses) and calcium phosphates (calcium hydroxyapatite, HA; tricalcium phosphate, TCP; and biphasic calcium phosphate, BCP). These materials differ in composition and physical properties fro each other and from bone (De Groot in Bioceramics of calcium phosphate, pp 100-114, 1983; Hench in J Am Ceram Soc 74:1487-1510, 1994; Jarcho in Clin Orthop 157:259-278, 1981; Daculsi et al. in Int Rev Cytol 172:129-191, 1996). Both stoichiometric and non-stoichiometric HA-based substitutes represent the current first choice in orthopedic surgery, in that they provide an osteoconductive scaffold to which chemotactic, circulating proteins and cells (e.g. mesenchymal stem cells, osteoinductive growth factors) can migrate and adhere, and within which progenitor cells can differentiate into functioning osteoblasts (Szpalski and Gunzburg in Orthopedics 25S:601-609, 2002). Indeed, HA may be extemporarily combined either with whole autologous bone marrow or PRP (platelet rich plasma) gel inside surgical theatre in order to favour and accelerate bone regeneration. A case of bifocal ulnar bone defect treated with stoichiometric HA-based bone substitute combined with PRP is reported in here, with a 12-month-radiographic follow-up. PMID:19711008

Paderni, Stefania; Terzi, S; Amendola, L

2009-09-01

151

Transdermal buprenorphine - a critical appraisal of its role in pain management  

PubMed Central

This paper reviews the current clinical data for the role of transdermal buprenorphine (BUP TDS) in the treatment of diverse acute and chronic pain syndromes. Literature searches were carried out using PubMed (1988 to June 2009). The published findings seem to support hypotheses regarding the rather unique analgesic mechanisms of buprenorphine as compared with pure ?-opioids like morphine and fentanyl. However, the exact mechanism of this analgesic efficacy still remains largely unknown despite recent advances in preclinical pharmacological studies. Such assessments have demonstrated the sustained antihyperalgesic effect of buprenorphine in diverse animal pain models. These findings are supported in a growing number of clinical studies of oral, intrathecal, intravenous, and Bup TDS. This review paper focuses almost entirely on the clinical experience concerning the transdermal administration of buprenorphine, although preclinical aspects are also addressed in order to provide a complete picture of the unique pharmacological properties of this analgesic drug. Mounting evidence indicates the appropriateness of Bup TDS in the treatment of diverse acute and chronic pain syndromes which have been less or not responsive to other opioids. Additionally, BUP TDS seems to hold great promise for other difficult-to-treat (pain) conditions, such as patients in the intensive care setting. However, its use is somewhat tempered by the occurrence of local skin reactions which have been shown to be often therapy resistant. Further studies are certainly warranted to identify even more precisely the clinical syndromes that are most sensitive to buprenorphine treatment, and to compare buprenorphine to other opioids in head-to-head trials of acute and chronic pain conditions.

Hans, Guy; Robert, Dominique

2009-01-01

152

[Opioid addiction: P300 assessment in treatment by methadone substitution].  

PubMed

The aim of this study was to assess cognitive functions in two clinical conditions, namely during heroin detoxification and during substitution treatment by methadone. Two groups of chronic heroin user inpatients, meeting DSM-III-R criteria for concurrent opiate dependence, were tested using an auditory oddball paradigm of P300. The first group (four women and six men) were drug-free and the second (five women, ten men) received methadone treatment. Patients were also compared to a control group of non-dependent healthy subjects (five women, nine men). The patients were recorded 6-10 days after the beginning of either detoxification or methadone treatment. There were significant P300 alterations in the two patient groups, with amplitude decrease and latency increase, at a time when self-reported signs of withdrawal were absent or minimal. Paradoxically, the reaction time was accelerated in the two groups of patients, who also showed increased discrimination errors. These abnormalities were found with a lesser degree in the methadone-treated group than in detoxification patients. PMID:11488228

Attou, A; Figiel, C; Timsit-Berthier, M

2001-06-01

153

The impact of cocaine use on outcomes in HIV-infected patients receiving buprenorphine/naloxone  

PubMed Central

BACKGROUND Cocaine use is common in opioid dependent HIV-infected patients but its impact on treatment outcomes in these patients receiving buprenorphine/naloxone is not known. METHODS We conducted a prospective study in 299 patients receiving buprenorphine/naloxone who provided baseline cocaine data and a subset of 266 patients who remained in treatment for greater than or equal to one quarter. Assessments were conducted at baseline and quarterly for one year. We evaluated the association between baseline and in-treatment cocaine use on buprenorphine/naloxone retention, illicit opioid use, antiretroviral adherence, CD4 counts, HIV RNA, and risk behaviors. RESULTS Sixty-six percent (197/299) of patients reported baseline cocaine use and 65% (173/266) of patients with follow-up data reported in-treatment cocaine use. Baseline and in-treatment cocaine use did not impact buprenorphine/naloxone retention, antiretroviral adherence, CD4 lymphocytes, or HIV risk behaviors. However, baseline cocaine use was associated with a 14.8 (95% CI=9.0–24.2) times greater likelihood of subsequent cocaine use (95% CI=9.0 – 24.2), a 1.4 (95% CI=1.02 – 2.00) times greater likelihood of subsequent opioid use, and higher Log10 HIV RNA (p? .016) over time. In-treatment cocaine use was associated with a 1.4 (95% CI=1.01–2.00) times greater likelihood of concurrent opioid use. CONCLUSIONS Given cocaine use negatively impacts opioid and HIV treatment outcomes, interventions to address cocaine use in HIV-infected patients receiving buprenorphine/naloxone treatment are warranted.

Sullivan, Lynn E.; Botsko, Michael; Cunningham, Chinazo; O'Connor, Patrick G.; Hersh, David; Mitty, Jennifer; Lum, Paula J.; Schottenfeld, Richard S.; Fiellin, David A.

2011-01-01

154

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

PubMed

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

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

2014-07-01

155

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

PubMed

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 ?g/l NX) was presumed to consist of injecting or snorting BNX abusers and the "Parenteral BPN" group (>50 ?g/l BPN, 0 ?g/l NX) of injecting or snorting BPN abusers, while the "Other BNX or BPN" group (?100 ?g/l NX, or ?50 ?g/l BPN combined with 0 ?g/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 ?g/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

Häkkinen, Margareeta; Heikman, Pertti; Ojanperä, Ilkka

2013-10-10

156

Buprenorphine and the transdermal system: the ideal match in pain management.  

PubMed

A system for the transdermal administration of the opioid drug buprenorphine has recently been introduced. Buprenorphine has physico-chemical properties, including a low molecular weight and high analgesic potency, that make it an excellent compound for transdermal drug delivery. The new technology (buprenorphine TDS, Transtec) is an advanced system that contains the active drug incorporated into a polymer matrix, which is at the same time the adhesive layer. The patch precisely controls the rate of drug delivery and produces stable plasma concentrations. It is available in three doses (release rates of 35, 52.5 and 70 microg/h), and the suggested duration of use per patch is three days. Buprenorphine TDS was developed for the treatment of moderate to severe cancer pain and severe pain which does not respond to non-opioid analgesics. Not only does this transdermal system provide excellent analgesia and a low incidence of adverse events, but its ease of use results in greater compliance. The patch provides excellent adhesion and has a low susceptibility to damage that might lead to toxicity or opioid abuse. PMID:12665118

Budd, Keith

2003-02-01

157

Principles and practices for treatment of cutaneous wounds with cultured skin substitutes  

Microsoft Academic Search

Background: Skin substitutes prepared from cultured skin cells and biopolymers may reduce requirements for donor skin autograft, and have been shown to be effective in treatment of excised burns, burn scars, and congenital skin lesions.Data Sources: Cultured skin substitutes (CSS) generate skin phenotypes (epidermal barrier, basement membrane) in the laboratory, and restore tissue function and systemic homeostasis. Healed skin is

Steven T Boyce; Glenn D Warden

2002-01-01

158

The use of skin substitutes in the treatment of the hand and upper extremity.  

PubMed

The introduction of skin substitutes in the last decade has dramatically changed how we think about the concept of "non-healing" wounds. Their use has improved prognosis and reduced morbidity in the treatment of open wounds. This article aims to summarize the development of tissue-engineered skin substitutes, discuss their use, and highlight some specific applications in different clinical settings. PMID:24839416

Capo, John T; Kokko, Kyle P; Rizzo, Marco; Adams, Julie E; Shamian, Ben; Abernathie, Brenon; Melamed, Eitan

2014-06-01

159

A Preliminary Study Comparing Methadone and Buprenorphine in Patients with Chronic Pain and Co-existent Opioid Addiction  

PubMed Central

Patients with opioid addiction who receive prescription opioids for treatment of chronic non-malignant pain present a therapeutic challenge. Fifty-four patients with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043) and compared to 5 in the buprenorphine group, none in the methadone group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term low-dose methadone or buprenorphine/naloxone treatment produced analgesia in patients with chronic pain and opioid addiction.

Neumann, Anne M.; Blondell, Richard D.; Jaanimagi, Urmo; Giambrone, Amanda K.; Homish, Gregory G.; Lozano, Jacqueline R.; Kowalik, Urszula; Azadfard, Mohammadreza

2013-01-01

160

Prenatal buprenorphine exposure decreases neurogenesis in rats.  

PubMed

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. PMID:24321744

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

161

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

PubMed Central

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

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

2013-01-01

162

Hemofiltration as a Substitute for Hemodialysis in the Treatment of End-Stage Renal Disease (ESRD).  

National Technical Information Service (NTIS)

Hemofiltration, as a substitute for hemodialysis for the treatment of patients with renal failure, is a technique by which an ultrafiltrate of plasma is obtained as a result of the hydrostatic pressure gradient exerted across a semipermeable membrane. In ...

H. Handelsman E. Carter

1986-01-01

163

Transdermal buprenorphine in clinical practice: a multicenter, noninterventional postmarketing study in the Czech Republic.  

PubMed

SUMMARY Aim: To evaluate the use of transdermal buprenorphine patches (Transtec®) in routine clinical practice. Patients & methods: A prospective, noninterventional, postmarketing study performed in the Czech Republic by 71 investigators in various clinical practice settings. Patients with chronic moderate-to-severe cancer pain, or chronic severe noncancer pain insufficiently controlled by nonopioids, were prescribed buprenorphine transdermal patch 35, 52.5 or 70 µg/h, and evaluated for 3 months. Additional analgesia and adjuvant/supportive treatments were allowed (physician discretion). Results: Data were evaluated for 630 patients (54% female, mean age 64 years). Most (>60%) patients had cancer-related pain. Noncancer pain was musculoskeletal (66.4%), neuropathic (25.9%) or nociceptive (6.0%). The mean dose of transdermal buprenorphine at study initiation was 40.6 µg/h. Compared with baseline (numerical rating scale [NRS]: 6.9), mean pain intensity (0-10 NRS) decreased significantly (p < 0.01) at 1 month (NRS: 2.9) and study end (NRS: 2.2). Most (>90%) patients rated pain relief as 'very good' or 'good', >97% of evaluable patients reported improvements in sleep quality and 87% of all evaluated patients were willing to continue transdermal buprenorphine after study completion. During the study, supplemental analgesic use remained unchanged; laxative/antiemetic use reduced (30.9% of patients [baseline] vs 23.3% [study end]). Twenty four nonserious adverse drug reactions (mainly local skin reactions) occurred in 19 (3%) patients. Conclusion: In routine clinical practice in the Czech Republic, transdermal buprenorphine was efficacious and well tolerated in patients with chronic moderate-to-severe cancer pain or chronic severe noncancer pain insufficiently controlled by nonopioids. PMID:24645818

Vondrá?ková, Dana

2012-03-01

164

The emerging buprenorphine epidemic in the United States.  

PubMed

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

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

2012-01-01

165

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

PubMed

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

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

2014-07-01

166

Comparison of Buprenorphine and Butorphanol Analgesia in the Eastern Red-Spotted Newt (Notophthalmus viridescens)  

PubMed Central

The experimental use of amphibian models in biomedical research increases yearly, but there is a paucity of reports concerning analgesic use in many of these species. In this study, buprenorphine given by intracoelomic injection and butorphanol added to the tank water were compared for analgesic effect in the eastern red-spotted newt after bilateral forelimb amputations. Newts undergoing anesthesia but not surgery and newts having surgery but not given analgesia postoperatively were used as control groups. Animals were tested for food consumption, spontaneous movement, response to tapping on the tank, response to being touched, and body posture. Both buprenorphine by intracoelomic injection and butorphanol in tank water significantly promoted resumption of normal behavior after bilateral surgical amputation of the forelimbs. The difference between analgesic treatment and no analgesic treatment was maintained until 72 h after surgery.

2009-01-01

167

Drug interactions associated with methadone, buprenorphine, cocaine, and HIV medications: Implications for pregnant women  

Microsoft Academic Search

Pregnancy in substance-abusing women with HIV\\/AIDS presents a complex clinical challenge. Opioid-dependent women need treatment with opioid therapy during pregnancy to protect the health of mother and developing fetus. However, opioid therapies, methadone and buprenorphine, may have drug interactions with some HIV medications that can have adverse effects leading to suboptimal clinical outcomes. Further, many opioid-dependent individuals have problems with

Elinore F. McCance-Katz

2011-01-01

168

Desipramine in Opioid-Dependent Cocaine Abusers Maintained on Buprenorphine vs Methadone  

Microsoft Academic Search

Background: Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and ef- fective pharmacotherapies are needed for this com- bined dependence. Methods: This 13-week, randomized, double-blind, pla- cebo-controlled trial evaluated the efficacy of desipra- mine hydrochloride (0 or 150 mg\\/d) plus buprenorphine hydrochloride (12 mg\\/d) or methadone hydrochloride (65 mg\\/d) in 180 opioid-dependent cocaine abusers (124

Alison H. Oliveto; Alan Feingold; Richard Schottenfeld; Peter Jatlow; Thomas R. Kosten

1999-01-01

169

Clinical pharmacology of buprenorphine: Ceiling effects at high doses  

Microsoft Academic Search

Objective: The purpose of this study was to characterize the acute effects of buprenorphine, an opioid partial (?-agonist, across a wide range of doses in comparison to methadone.Method: Healthy adult male volunteers, who had experience with but were not physically dependent on opioids, participated while residing on a closed research unit. Four subjects received buprenorphine (0, 1, 2, 4, 8,

Sharon L Walsh; Kenzie L Preston; Maxine L Stitzer; Edward J Cone; George E Bigelow

1994-01-01

170

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

PubMed Central

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.

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

171

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

PubMed Central

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.

2011-01-01

172

Change in symptoms of erectile dysfunction in depressed men initiating buprenorphine therapy?  

PubMed Central

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

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

2014-01-01

173

Cocaine Use Reduction with Buprenorphine (CURB): Rationale, design, and methodology?  

PubMed Central

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

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

2013-01-01

174

Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain.  

PubMed

Buprenorphine is an opioid that has a complex and unique pharmacology which provides some advantages over other potent mu agonists. We review 12 reasons for considering buprenorphine as a frontline analgesic for moderate to severe pain: (1) Buprenorphine is effective in cancer pain; (2) buprenorphine is effective in treating neuropathic pain; (3) buprenorphine treats a broader array of pain phenotypes than do certain potent mu agonists, is associated with less analgesic tolerance, and can be combined with other mu agonists; (4) buprenorphine produces less constipation than do certain other potent mu agonists, and does not adversely affect the sphincter of Oddi; (5) buprenorphine has a ceiling effect on respiratory depression but not analgesia; (6) buprenorphine causes less cognitive impairment than do certain other opioids; (7) buprenorphine is not immunosuppressive like morphine and fentanyl; (8) buprenorphine does not adversely affect the hypothalamic-pituitary-adrenal axis or cause hypogonadism; (9) buprenorphine does not significantly prolong the QTc interval, and is associated with less sudden death than is methadone; (10) buprenorphine is a safe and effective analgesic for the elderly; (11) buprenorphine is one of the safest opioids to use in patients in renal failure and those on dialysis; and (12) withdrawal symptoms are milder and drug dependence is less with buprenorphine. In light of evidence for efficacy, safety, versatility, and cost, buprenorphine should be considered as a first-line analgesic. PMID:22809652

Davis, Mellar P

2012-01-01

175

Results of a Pilot Randomized Controlled Trial of Buprenorphine For Opioid Dependent Women in the Criminal Justice System  

PubMed Central

Aims Recent studies have demonstrated the efficacy of both methadone and buprenorphine when used with opioid dependent men transitioning from prison to the community, but no studies have been conducted with women in the criminal justice (CJ) system. The aim of this study was to determine the efficacy of buprenorphine for relapse prevention among opioid dependent women in the CJ system transitioning back to the community. Methods 36 women under CJ supervision were recruited from an inpatient drug treatment facility that treats CJ individuals returning back to the community. Nine were enrolled in an open label buprenorphine arm then 27 were randomized to buprenorphine (n=15) or placebo (n=12; double-blind). All women completed baseline measures and started study medication prior to release. Participants were followed weekly, provided urine drug screens (UDS), received study medication for 12 weeks, and returned for a 3 month follow-up. Intent-to-treat analyses were performed for all time points through end-of-treatment (EOT). Results The majority of participants were Caucasian (88.9%), young (M±SD=31.8±8.4 years), divorced/separated (59.2%) women with at least a high school/GED education (M±SD =12±1.7 years). GEE analyses showed that buprenorphine was efficacious in maintaining abstinence across time compared to placebo. At End of Treatment, 92% of placebo and 33% of active medication participants were positive for opiates on urine drug screen (Chi-Square = 10.9, df=1; p<0.001). However, by the three month follow-up point, no differences were found between the two groups, with 83% of participants at follow-up positive for opiates. Conclusions Women in the CJ system who received buprenorphine prior to release from a treatment facility had fewer opiate positive UDS through the 12-weeks of treatment compared to women receiving placebo. Initiating buprenorphine in a controlled environment prior to release appears to be a viable strategy to reduce opiate use when transitioning back to the community.

Cropsey, Karen L.; Lane, Peter S.; Hale, Galen J.; Jackson, Dorothy O.; Clark, C. Brendan; Ingersoll, Karen S.; Islam, M. Aminul; Stitzer, Maxine L.

2011-01-01

176

Behavioral treatment of voyeurism and possible symptom substitution  

Microsoft Academic Search

Presents a case study that describes the relatively successful treatment of voyeuristic behaviors using behavioral techniques. A 44-yr-old black male had been a peeping tom since the age of 13. He was of borderline mental retardation with an IQ of 77. He and his wife were asked to keep a record of his peeping urges and fantasies and from this

John Stoudenmire

1973-01-01

177

Opioid rotation from high-dose morphine to transdermal buprenorphine (Transtec) in chronic pain patients.  

PubMed

Opioid rotation is increasingly becoming an option to improve pain management especially in long-term treatment. Because of insufficient analgesia and intolerable side effects, a total of 42 patients (23 male, 19 female; mean age 64.1 years) suffering from severe musculoskeletal (64%), cancer (21%) or neuropathic (19%) pain were converted from high-dose morphine (120 to >240 mg/day) to transdermal buprenorphine. The dose of buprenorphine necessary for conversion (at least 52.5 microg/h) was titrated individually by the treating physician. No conversion recommendations were given and the treating physician used his or her own judgment for dose adjustment. Pain relief, overall satisfaction and quality of sleep (very good, good, satisfactory, poor, or very poor), and the incidence and severity of adverse drug reactions over a period of at least 10 weeks and up to 1 year was assessed. Following rotation, patients experiencing good/very good pain relief increased from 5% to 76% (P < 0.001). Only 5% reported insufficient relief. Relief was achieved with buprenorphine alone in 77.4%, while 17% needed an additional opioid for breakthrough pain. Sleep quality (good/very good) increased from 14% to 74% (P < 0.005). Adverse effects were reported in 11.9%, mostly because of local irritation, did not result in termination of therapy. Neither tolerance nor refractory effect following rotation from morphine to buprenorphine was noted. Conversion tables with a fixed conversion ratio are of limited value in patients treated with high-dose morphine. PMID:17559481

Freye, Enno; Anderson-Hillemacher, Astrid; Ritzdorf, Ingrid; Levy, Joseph Victor

2007-06-01

178

2-(substituted piperazinylalkyl).beta.-carbolines useful in treatment of psychological disorders  

US Patent & Trademark Office Database

The .beta.-carbolines N-substituted in 2-position with a piperidinyl alkyl group are antipsychotic agents and anxiolytic agents with minimal extrapyramidal side effects, useful in the treatment of psychological disorders such as paranoia and schizophrania as well as general states of anxiety.

1987-05-05

179

Effects of Buprenorphine, Meloxicam, and Flunixin Meglumine as Postoperative Analgesia in Mice  

PubMed Central

C57BL/6NCrl male mice (n = 60; age, 6 to 7 wk) underwent partial hepatectomy or no surgery and were given 1 of 3 analgesics pre- and postoperatively. Food and water consumption, body weight, running wheel activity, locomotor activity, and serum corticosterone concentrations were measured before and after surgery. Mice that were surgically manipulated weighed significantly less on days 1 through 3 after surgery than did mice not manipulated surgically. On the day of surgery, the surgery groups consumed significantly less feed (–1.5 ± 0.35 g) than did nonsurgery groups. There were no differences in water consumption on any day between surgery and nonsurgery groups or among the 3 analgesic groups. For running wheel activity, significant decreases in the surgery groups were seen at day 1 after surgery compared with baseline. Surgery groups that received buprenorphine and meloxicam returned to baseline activity levels on day 2 after surgery. Open-field testing revealed no significant differences in locomotor activity in any groups; however, posttreatment locomotor activity in the buprenorphine nonsurgery group was increased compared with baseline, and posttreatment locomotor activity in the flunixin meglumine surgery group was decreased compared with baseline. Serum corticosterone concentrations were within normal limits regardless of treatment in all groups. Comparison of the overall results indicated that meloxicam and buprenorphine, at the dose given, appear to be suitable postoperative analgesics for partial hepatectomy in mice. Flunixin meglumine at the given dosage (2.5 mg/kg) may not provide adequate analgesia for partial hepatectomy.

Tubbs, Jacquelyn T; Kissling, Grace E; Travlos, Greg S; Goulding, David R; Clark, James A; King-Herbert, Angela P; Blankenship-Paris, Terry L

2011-01-01

180

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

PubMed

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

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

2013-08-01

181

Anaphylaxis after the injection of buprenorphine.  

PubMed

Cause of death rulings in cases when the concentration of a drug or drugs is higher than observed following therapeutic use are generally straightforward "drug deaths." However, when toxicology testing identifies drug concentrations consistent with therapeutic use or detects no drugs at all, then the cause of death determination is more complicated. Given the rapidity and protean manifestations of anaphylaxis, it should be considered in deaths where no other cause of death is apparent in a suspected drug death. This article reports two cases where an anaphylactic reaction was observed following either the actual or alleged use of therapeutic formulations of buprenorphine intravenously. PMID:23550514

Boggs, Cassie L; Ripple, Mary G; Ali, Zabiullah; Brassell, Melissa; Levine, Barry; Jufer-Phipps, Rebecca; Doyon, Suzanne; Fowler, David R

2013-09-01

182

Buprenorphine Prescribing Practices and Exposures Reported to a Poison Center: Utah, 2002-2011. Morbidity and Mortality Weekly Report Volume 61, No. 49.  

National Technical Information Service (NTIS)

Buprenorphine is an effective medication for the treatment of opioid dependence. Its use has increased in the United States as a result of the Drug Addiction Treatment Act of 2000, which allowed physicians to prescribe certain medications as part of offic...

2012-01-01

183

Consumer Attitudes about Opioid Addiction Treatment: A focus group study in New York City  

PubMed Central

Objective To develop effective programs for people who are opioid-dependent and to impact the opioid epidemic in New York City, it is crucial that we monitor attitudes about opioid addiction treatments among opioid users who have experienced barriers to engagement and retention in addiction treatment. Design We conducted a qualitative study using focus groups. Methods We conducted six focus groups in three needle exchanges in New York City, which were audio recorded, transcribed, and systematically coded. We report on the main themes related to the study objectives. Participants Participants of each needle exchange who were opioid-dependent and had some knowledge of both methadone and buprenorphine were eligible. Results There were four main findings. Participants felt: (1) buprenorphine is an appropriate option only for those heroin users who are motivated to stop using; (2) they have less control over their addiction treatment with methadone than they would have with buprenorphine; (3) buprenorphine treatment is not accessible to many New York City residents who would benefit from this treatment; and (4) lack of access to buprenorphine treatment is the cause of treatment-related diversion. Conclusions Both methadone maintenance and buprenorphine treatment opportunities are necessary to address the diverse treatment needs of opioid-dependent people in New York City. However, the current medical model of buprenorphine treatment may be too restrictive for some opioid-dependent people, and may be contributing to the use of illicit buprenorphine. New models to deliver buprenorphine treatment may address these problems.

Weiss, Linda; Egan, James E.; Lopez, Carolina; Favaro, Jamie; Cordero, Robert; Cunningham, Chinazo

2014-01-01

184

A Comparison of Cigarette Smoking Profiles in Opioid-Dependent Pregnant Patients Receiving Methadone or Buprenorphine  

PubMed Central

Introduction: Little is known about the relationship between cigarette smoking and agonist treatment in opioid-dependent pregnant patients. The objective of this study is to examine the extent to which cigarette smoking profiles differentially changed during the course of pregnancy in opioid-dependent patients receiving either double-blind methadone or buprenorphine. Patients were participants in the international, randomized controlled Maternal Opioid Treatment: Human Experimental Research (MOTHER) study. Methods: A sample of opioid-maintained pregnant patients (18–41 years old) with available smoking data who completed a multisite, double-blind, double-dummy, randomized controlled trial of methadone (n = 67) and buprenorphine (n = 57) between 2005 and 2008. Participants were compared on smoking variables based on opioid agonist treatment condition. Results: Overall, 95% of the sample reported cigarette smoking at treatment entry. Participants in the two medication conditions were similar on pretreatment characteristics including smoking rates and daily cigarette amounts. Over the course of the pregnancy, no meaningful changes in cigarette smoking were observed for either medication condition. The fitted difference in change in adjusted cigarettes per day between the two conditions was small and nonsignificant (? = ?0.08, SE = 0.05, p = .132). Conclusions: Results support high rates of smoking with little change during pregnancy among opioid-dependent patients, regardless of the type of agonist medication received. These findings are consistent with evidence that suggests nicotine effects, and interactions may be similar for buprenorphine compared with methadone. The outcomes further highlight that aggressive efforts are needed to reduce/eliminate smoking in opioid-dependent pregnant women.

2013-01-01

185

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

PubMed Central

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

Freitas, Gabrielle C.; Carregaro, Adriano B.; Gehrcke, Martielo I.; De La Corte, Flavio D.; Lara, Valeria M.; Pozzobon, Ricardo; Brass, Karin E.

2011-01-01

186

Comparison of oral and subcutaneous administration of buprenorphine and meloxicam for preemptive analgesia in cats undergoing ovariohysterectomy  

Microsoft Academic Search

Objective - To compare the effectiveness of preoperative PO and SC administration of buprenorphine and meloxicam for prevention of postoperative pain-associated behaviors in cats undergoing ovariohysterectomy. Design - Randomized controlled study. Animals - 51 female cats (4 to 60 months old; weight range, 1.41 to 4.73 kg [3.1 to 10.4 lb]). Procedure - Cats received 1 of 5 treatments at

Adam D. Gassel; Karen M. Tobias; Christine M. Egger; Rohrbach Barton W

2005-01-01

187

Effects of buprenorphine and an alternative nondrug reinforcer, alone and in combination on smoked cocaine self-administration in monkeys  

Microsoft Academic Search

The abuse of smoked cocaine base, also known as ‘crack’, continues to be a major public health problem and to date the success of pharmacological or behavioral interventions has been limited. The purpose of this study was to evaluate the efficacy of a behavioral (alternative reinforcer-saccharin) and pharmacological (0.01 mg\\/kg buprenorphine) treatment alone and in combination. Five adult male rhesus

Joshua S. Rodefer; Adande J. Mattox; Sherry S. Thompson; Marilyn E. Carroll

1997-01-01

188

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

PubMed

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. PMID:23952506

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

2013-08-01

189

Treatment of chronic sternal fistulae following cardiac surgery with a bone substitute.  

PubMed

Chronic sternal infection is a relatively rare complication following cardiac surgery that can cause high morbidity and mortality and can require repeated surgical procedures, including sternal resection, to resolve. However, preserving sternal integrity is essential, particularly in children. A variety of conservative treatments for this complication of cardiac surgery have been reported. Here, we report three cases of children in whom a bone substitute containing tricalcium phosphate and hydroxyapatite was used to fill sternal defects. After extensive surgical debridement, this method yielded primary wound closure with good resolution, preventing the recurrence of sternal infection. PMID:24049817

Lamas, M J; Centella, T

2013-06-01

190

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

PubMed Central

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.

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

191

Buprenorphine TDS: the clinical development rationale and results.  

PubMed

Buprenorphine, a powerful opioid, is newly available for delivery in a transdermal formulation. The transdermal system's matrix patch provides rate-controlled administration of the drug. Three double-blind, placebo-controlled trials were conducted to evaluate efficacy and tolerability of the buprenorphine transdermal system (buprenorphine TDS, Transtec). A total of 445 patients were enrolled in the studies. All suffered from moderate to severe and very severe pain, both cancer- or non-cancer-related. The percentage of responders increased as the rate of buprenorphine delivered by the transdermal system rose, ranging from a 29% (cancer) and 36% (non-cancer) response rate associated with the lowest dose (35 microg/h), to 40% (cancer) and 46% (non-cancer) with the highest dose (70 microg/h). Patients receiving buprenorphine TDS slept longer, uninterrupted by pain, than patients from the placebo group. Systemic adverse effects reported in the drug cohorts included nausea, vomiting and dizziness, and were typical of those reported in other studies of opioids; local adverse events, most commonly erythema and pruritus, were transient and mild to moderate. In an open-label, follow-up trial, in which 239 patients from the original clinical studies participated, 90% of patients reported that their analgesia was satisfactory or even better over a mean duration of 4.7 months; nearly 95% of patients found the patch to be user-friendly. The new buprenorphine TDS appears to be an important new modality for administering analgesia in patients with non-acute pain. PMID:12665119

Radbruch, Lukas; Vielvoye-Kerkmeer, Ans

2003-02-01

192

Acute effects of intramuscular and sublingual buprenorphine and buprenorphine\\/naloxone in non-dependent opioid abusers  

Microsoft Academic Search

Rationale  Buprenorphine is a partial mu opioid receptor agonist with clinical efficacy as a pharmacotherapy for opioid dependence. A\\u000a sublingual combination formulation was developed containing buprenorphine and naloxone with the intent of decreasing abuse\\u000a liability in opioid-dependent individuals. However, the addition of naloxone may not limit abuse potential of this medication\\u000a when taken by individuals without opioid physical dependence.\\u000a \\u000a \\u000a \\u000a \\u000a Objectives  The present

Angela N. Duke; Christopher J. Correia; Sharon L. Walsh; George E. Bigelow; Eric C. Strain

2010-01-01

193

Buprenorphine Outpatient Outcomes Project: can Suboxone be a viable outpatient option for heroin addiction?  

PubMed Central

Background Opioid dependence treatment traditionally involves methadone clinics, for which dispensing schedules can be cumbersome. Buprenorphine, a partial agonist of the mu receptor and antagonist of the kappa receptor, is a potential outpatient alternative to methadone. Funded by a grant from the State of Maryland's Community Health Resources Commission (CHRC), the Buprenorphine Outpatient Outcomes Project (BOOP) evaluates the outcome of Suboxone (buprenorphine/naloxone) treatment on abstinence from heroin use, rates of emergency room visits and hospitalizations, legal issues, and quality of life. Methods Active heroin users were recruited between June 2007 and June 2010 and induction therapy with Suboxone was instituted during hospitalization. Once discharged, patients were followed as outpatients for maintenance treatment and counseling. Data were collected from electronic medical records, Maryland state legal records, and SF-36® Health Surveys regarding several parameters and patients were categorized according to duration of treatment with Suboxone into one of three groups: <1 month, 1–3 months, and >3 months. Results A total of 220 participants were included in the study. The age range of participants was 18–67 years with most being African American males. Eighty-three (38%) remained in the study for at least 1 month, with 37 of the 83 (45%) remaining in treatment for >3 months. Ten of the 37 (27%) never relapsed after their longest period of abstinence from heroin. During the first year after initiating treatment with Suboxone, hospitalization and emergency room visit rates for all 220 participants decreased by 45 and 23%, respectively, as compared to the year prior to starting treatment. The number of legal charges for drug possession decreased from 70 to 62. Anecdotally, the quality of life seemed to improve in those who were treated with Suboxone for longer periods of time and received regular counseling. Conclusion Overall, Suboxone is an effective treatment method for heroin addiction and is a viable outpatient therapy option. Individualized treatment plans and counseling must be implemented for maximum benefits to be seen. Retention of patients for a long duration of therapy was difficult, but for those who did remain, benefits were seen in overall health, abstinence from heroin use, cognition, and quality of life.

Sittambalam, Charmian D.; Vij, Radhika; Ferguson, Robert P.

2014-01-01

194

Mental Health Treatment Program Locator  

MedlinePLUS

... Treatment Facility Locator Buprenorphine Physician Locator Find a Facility in Your State To locate the mental health ... Service . Privacy Policy . Home | About the Locator | Find Facilities Near You | Find Facilities by City, County, State ...

195

Psychomotor effects of ketorolac in comparison with buprenorphine and diclofenac.  

PubMed Central

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.

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

1989-01-01

196

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

PubMed Central

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

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

2011-01-01

197

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

PubMed Central

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.

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

198

Cationized IVIg as a potential substitute to IVIg for the treatment of experimental immune thrombocytopenia.  

PubMed

In this study, we evaluated the possibility of using cationized IVIg (cIVIg) instead of IVIg as a more effective therapy for the treatment of experimental immune thrombocytopenia in mice. The pharmacokinetics (PK) and biodistribution of cIVIg and IVIg in mice were compared. cIVIg displayed a shorter plasma half-life and an increased organ uptake in both the spleen and liver compared to IVIg, suggesting that cIVIg could be more potent than IVIg to prevent platelet clearance in a mouse model of thrombocytopenia. However, although the biodistribution of cIVIg in the spleen and liver was improved, its ability to prevent platelet clearance in mice remained similar to that of IVIg. Altogether, our data demonstrate the possibility of using chemical cationization of IVIg preparations to increase organ uptake, and also highlight the challenges of developing effective substitutes to IVIg. PMID:23665226

Trépanier, Patrick; St-Amour, Isabelle; Bazin, Renée

2013-08-01

199

Psychiatric and medical comorbidities, associated pain, and health care utilization of patients prescribed buprenorphine.  

PubMed

This study describes the comorbidities and health care utilization of individuals treated with buprenorphine using the 2007-2009 MarketScan Research Databases. Buprenorphine recipients had a high prevalence of comorbidities associated with chronic pain, including back problems (42%), connective tissue disease (24-27%), and nontraumatic joint disorders (20-23%). Approximately 69% of recipients filled prescriptions for opioid agonist medications in the 6 months before buprenorphine initiation. Buprenorphine recipients were frequently diagnosed with anxiety (23-42%) and mood disorders (39-51%) and filled prescriptions for antidepressants (47-56%) and benzodiazepines (47-56%) at high rates. Surprisingly, only 53-54% of patients filling a prescription for buprenorphine had a coded opioid abuse/dependence diagnosis. Research is needed to better understand buprenorphine's effectiveness in the context of prescription drug abuse and the best way to coordinate services to address the patient's comorbid addiction, pain, and psychiatric illnesses. PMID:23265445

Mark, Tami L; Dilonardo, Joan; Vandivort, Rita; Miller, Kay

2013-01-01

200

Pharmacokinetics of 2 Formulations of Buprenorphine in Macaques (Macaca mulatta and Macaca fascicularis)  

PubMed Central

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.

Nunamaker, Elizabeth A; Halliday, Lisa C; Moody, David E; Fang, Wenfang B; Lindeblad, Matthew; Fortman, Jeffrey D

2013-01-01

201

Reassessment of buprenorphine in conditioned place preference: temporal and pharmacological considerations  

Microsoft Academic Search

Rationale Buprenorphine is widely used as an analgesic drug and it is also increasingly considered for maintenance and detoxification of heroin addicts. It is a potent µ-receptor partial agonist with a long duration of action. An inverted U-shaped dose-effect curve for buprenorphine conditioned place preference (CPP) has been shown previously. Objectives We re-evaluated the CPP effects of buprenorphine by taking

Thomas M. Tzschentke

2004-01-01

202

Motivational properties of buprenorphine as assessed by place and taste conditioning in rats  

Microsoft Academic Search

Buprenorphine, a mixed agonist-antagonist opioid with considerable analgesic activity, is currently indicated as a therapeutic\\u000a agent with low abuse potential. Nevertheless, buprenorphine abuse has been recently reported from some countries. Thus the\\u000a present experiments were performed to characterize further the motivational properties of buprenorphine in rats. Rewarding\\u000a and aversive effects were assessed by place preference and taste aversion conditioning, respectively.

M. Gaiardi; M. Bartoletti; A. Bacchi; C. Gubellini; M. Babbini

1997-01-01

203

A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network  

Microsoft Academic Search

AIMS: The clinical effectiveness of buprenorphine-naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network.\\u000aDESIGN: Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2 : 1 ratio favoring bup-nx,

Walter Ling; Leslie Amass; Steve Shoptaw; Jeffrey J. Annon; Maureen Hillhouse; Dean Babcock; Greg Brigham; Judy Harrer; Malcolm S. Reid; Joan A. Muir; Betty J. Buchan; Debbie Orr; George Woody; Jonathan Krejci; Douglas M. Ziedonis

2005-01-01

204

Evaluation of an improved sustained-release buprenorphine formulation for use in mice.  

PubMed

Objective-To evaluate analgesic effects of an improved sustained-release buprenorphine (BUP-SR) formulation administered to mice. Animals-36 male Swiss-Webster mice. Procedures-Mice were assigned to each of 3 treatment groups (n = 12 mice/group). Treatments were administered SC (vehicle [control treatment], 1.5 mg of buprenorphine hydrochloride [BUP-HCl]/kg, and 1.5 mg of BUP-SR/kg). Mice were evaluated (total activity, gastrointestinal tract motility, respiratory rate, cataleptic behavior, and tall-flick and hot plate nociception tests) to determine behavioral and physiologic responses at 4, 24, and 48 hours after treatment administration. Body weight and respiratory rate were measured before and at each time point after treatment administration. Results-SC administration of BUP-SR resulted in significant antinociception effects for 48 hours for the hot plate and tall-flick nociception tests without substantial adverse effects. Gastrointestinal tract motility and total activity were higher at 4 hours for mice receiving BUP-SR than for mice receiving the vehicle, but values were the same between these groups at 24 and 48 hours. The BUP-SR group had a lower respiratory rate than did the control group at all times after treatment administration. Mice treated with BUP-SR had no significant changes in body weight during the study, whereas mice treated with BUP-HCl had a significant decrease in body weight at 24 and 48 hours. Conclusions and Clinical Relevance-BUP-SR administration resulted in antinociception effects for 48 hours. Results of this study indicated that the improved BUP-SR formulation could be safely administered SC and conferred superior analgesia, compared with that for BUP-HCl, in mice. PMID:24959727

Healy, Jason R; Tonkin, Jennifer L; Kamarec, Stacey R; Saludes, Mitchell A; Ibrahim, Sherif Y; Matsumoto, Rae R; Wimsatt, Jeffrey H

2014-07-01

205

Suprathel-an innovative, resorbable skin substitute for the treatment of burn victims.  

PubMed

Autologous split skin grafts are the most reliable method for closing third degree burns. Under this scheme, donor sites as well as second degree burns under conservative treatment, however, would benefit from rapid wound closure. For this treatment, biological as well as synthetic materials are available. For the improvement of these materials, primary goals are pain reduction and easy handling in the absence of biological risk. From a synthetic copolymer mainly based on DL-lactic acid a new skin substitute was developed, marketed as Suprathel. Within the scope of a bicentric study Suprathel was compared versus paraffin gauze intraindividually applied on split skin donor sites. Wound pain was measured on the Visual Pain Analog Scale over a period of 10 days as the critical criterion. Accordingly Suprathel versus Omiderm were compared on second degree burns (degree 2a, partial thickness burns). In both study parts, Suprathel significantly reduced pain. Its easy handling was superior compared to other materials. The Suprathel membrane adhered rapidly to the wound thus protecting against infections and promoting wound healing. No allergic reactions were observed. The ability of the material to resorb ensured pain-free removal after complete healing of the wound. PMID:17084030

Uhlig, C; Rapp, M; Hartmann, B; Hierlemann, H; Planck, H; Dittel, K-K

2007-03-01

206

Buprenorphine: dose-related effects on cocaine and opioid use in cocaine-abusing opioid-dependent humans  

Microsoft Academic Search

Fifteen subjects dependent on both opioids and cocaine completed an ascending and tapering schedule of buprenorphine dosing, with maintenance for 21 days at each dose of buprenorphine (4, 8, 12, 16 mg sublingual daily) during both ascending and tapering phases. Higher doses of buprenorphine led to greater reductions in opioid use: 64.7% of subjects were opioid abstinent for 3 weeks

Richard S. Schottenfeld; Juliana Pakes; Douglas M. Ziedonis; Thomas R. Kosten

1993-01-01

207

Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine.  

PubMed

Buprenorphine was not used widely in clinical practice over many years, mainly due to analgesic potency and clinical safety concerns based on misinterpreted animal data. Contrary to previous concerns, however, no analgesic ceiling effect and no antagonism of combined pure mu-opioid receptor agonists is seen within the therapeutic dose range. In recent studies, buprenorphine could be effectively and safely combined with full mu-agonists, and switching between buprenorphine and another opioid provided comparable pain relief based on equianalgesic doses. Moreover, buprenorphine exerts an antihyperalgesic effect, which is due -- at least in part -- to antagonistic activity at kappa-opioid receptors. Buprenorphine pharmacokinetics are not altered by advanced age or renal dysfunction. In addition, the risk of respiratory depression is lower than with other opioids including morphine, hydromorphone, methadone and fentanyl. Unlike morphine and fentanyl, there is no immunosuppressive activity with buprenorphine at therapeutic analgesic doses. Transdermal buprenorphine has significantly improved the clinical use of the drug, providing continuous buprenorphine release for up to 96 h. In clinical trials, patients receiving transdermal buprenorphine experienced significantly greater pain relief, better sleep, and a reduced need for rescue therapy, compared to placebo. Large-scale post-marketing studies have confirmed the effectiveness of transdermal buprenorphine in treating moderate-to-severe cancer and non-cancer pain including neuropathic syndromes. Finally, the comparably low incidence of CNS adverse events and constipation, and the possibility of use in severe renal dysfunction without a need for dose adjustment make buprenorphine well suited for chronic pain management in at-risk patients, such as diabetics, elderly or renally impaired individuals including those requiring haemodialysis. PMID:18567516

Kress, Hans G

2009-03-01

208

Buprenorphine and norbuprenorphine findings in hair during constant maintenance dosage  

Microsoft Academic Search

It is still a matter of debate whether a positive correlation between the dose and the amount of drug in the hair exists.\\u000a Drugs such as buprenorphine (BUP) used under controlled conditions present an opportunity to prove a possible relationship.\\u000a Due to discrepant findings of BUP\\/norbuprenorphine (NBUP) ratios in hair, in vitro degradation of both analytes in diluted\\u000a acid was

Gisela Skopp; Anja Kniest; Joerg Haisser; Karl Mann; Derik Hermann

2011-01-01

209

C10-substituted camphors and fenchones by electrophilic treatment of 2-methylenenorbornan-1-ols: enantiospecificity, scope, and limitations.  

PubMed

Valuable chiral sources of C(10)-substituted camphors and C(10)-substituted fenchones can be straightforwardly obtained by treatment of an appropriate, easily obtainable, camphor- or fenchone-derived 2-methylenenorbornan-1-ol with an electrophilic reagent. The process takes place via a tandem regioselective carbon-carbon double-bond addition/stereocontrolled Wagner-Meerwein rearrangement. A complete study of the enantiospecificity, scope, and limitations of this process, as well as about the role played by the hydroxyl group attached at the C(1) bridgehead position of the starting 2-methylenenorbornan-1-ols, has been realized. The feasibility of the described methodology has been exemplified by the highly efficient enantiospecific preparation of several interesting C(10)-halogen-, C(10)-O-, C(10)-S-, C(10)-Se-, or C(10)-C-substituted camphors and fenchones. PMID:12585887

de la Moya Cerero, Santiago; García Martínez, Antonio; Teso Vilar, Enrique; García Fraile, Amelia; Lora Maroto, Beatriz

2003-02-21

210

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

PubMed

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. PMID:23471956

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

2013-05-01

211

Short communication Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users  

Microsoft Academic Search

Buprenorphine (Subutex®) is widely abused in Finland. A combination of buprenorphine plus naloxone (Suboxone®) has been available since late 2004, permitting a comparison of the abuse of the two products among untreated intravenous (IV) users. A survey was distributed to attendees at a Helsinki needle exchange program over 2-weeks in April, 2005, At least 30% were returned anonymously. Survey variables

Hannu Alho; David Sinclair; Erkki Vuori; Antti Holopainen

212

Abuse liability of buprenorphine–naloxone tablets in untreated IV drug users  

Microsoft Academic Search

Buprenorphine (Subutex®) is widely abused in Finland. A combination of buprenorphine plus naloxone (Suboxone®) has been available since late 2004, permitting a comparison of the abuse of the two products among untreated intravenous (IV) users. A survey was distributed to attendees at a Helsinki needle exchange program over 2-weeks in April, 2005, At least 30% were returned anonymously. Survey variables

Hannu Alho; David Sinclair; Erkki Vuori; Antti Holopainen

2007-01-01

213

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

ERIC Educational Resources Information Center

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

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

2006-01-01

214

Illicit Use of Buprenorphine in a Community Sample of Young Adult Non-Medical Users of Pharmaceutical Opioids  

PubMed Central

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.

Daniulaityte, Raminta; Falck, Russel; Carlson, Robert G.

2011-01-01

215

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

PubMed Central

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

Springer, Sandra A.; Bruce, Robert D.

2008-01-01

216

Evaluation of the physical properties of water treatment residue for use as a soil substitute compared with decomposed granite soil  

Microsoft Academic Search

To evaluate water treatment residue (WTR) as a soil substitute material, its physical properties were investigated and compared with decomposed granite soil (DGS). For comparison purposes, relative gas diffusivity (D\\/D0), saturated hydraulic conductivity (Ks), water retention curve, porosity and readily available water were measured for both the WTR and the DGS. The measured D\\/D0, Ks, water retention ability and porosity

Seok-Gon Park; Mizue Ohashi; Kiyoshi Kurosawa; Young-Jin Kim; Hisashi Yahata

2010-01-01

217

Transdermal buprenorphine in clinical practice: a multicenter, postmarketing study in the Czech Republic, with a focus on neuropathic pain components.  

PubMed

SUMMARY Aim: A 3-month evaluation of transdermal buprenorphine (Transtec®) in routine clinical practice in the Czech Republic. Patients & methods: A prospective, noninterventional, postmarketing study performed in 45 clinical practices (82 investigators). Buprenorphine transdermal patches 35, 52.5 or 70 µg/h were prescribed to patients with chronic moderate-to-severe cancer pain or chronic severe noncancer pain insufficiently controlled by nonopioids. Additional analgesia and adjuvant/supportive treatment was allowed at the discretion of the physician. Results: Data were evaluated for 617 patients (59% female, mean age 65 years). 55% of patients had cancer-related pain; 33% of all patients had neuropathic pain components. At month 3 (study end), mean pain intensity was reduced significantly from baseline (p < 0.01). Similar effectiveness outcomes were observed in patients (n = 203) with neuropathic pain components. Most patients rated pain relief as 'very good' (47.7%) or 'good' (45.7%) and >98% of evaluable patients reported improvements in sleep quality. During the study, supplemental analgesic use remained unchanged; laxative/antiemetic use was reduced (25.1% of patients [baseline] vs 17.7% [study end]). A total of 22 nonserious adverse drug reactions (mainly local skin reactions) occurred in 14 (2.3%) patients; no previously unknown adverse drug reactions occurred. Conclusion: In routine clinical practice, transdermal buprenorphine provided efficacious analgesia and was well-tolerated in patients with chronic moderate-to-severe cancer pain or chronic severe nonmalignant pain insufficiently controlled by nonopioids, including pain with neuropathic components. PMID:24645819

Hakl, Marek

2012-03-01

218

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

PubMed Central

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 ?-opiod agonist and a ?-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.

2012-01-01

219

Comparison of Intravenous Buprenorphine and Methadone Self-administration by Recently Detoxified Heroin Abusers  

PubMed Central

Although buprenorphine is used worldwide as a safe and effective maintenance medication for opioid dependence, some countries have reported a growing incidence of abuse of this medication. Buprenorphine is considered to have lower abuse potential because of its partial agonist profile, but no studies have directly compared the reinforcing effects of buprenorphine with those of full mu opioid agonists in humans. The present double-blind, placebo-controlled, inpatient study compared the reinforcing and subjective effects of intravenously administered buprenorphine (0.5, 2 and 8 mg) and methadone (5, 10, and 20 mg). Participants (N=6) were detoxified from heroin during the first 1-2 weeks after admission. During subsequent weeks, participants received a sample drug dose and $20 on Monday, and they could self-administer either the sampled dose or $20 during one choice session per day on Thursday and Friday. Participants responded under a modified progressive ratio schedule during each choice session. All active doses maintained higher progressive ratio break points (largest completed ratio) than placebo. There were no significant differences in break point values between buprenorphine and methadone or among the different doses of drug. However, several subjective ratings, including “Good Drug Effect,” “High,” and “Liking” dose-dependently increased after administration of buprenorphine and methadone. The peak ratings for these effects did not significantly differ for the two drugs. These results demonstrate that under these experimental conditions, buprenorphine and methadone were equally effective in producing reinforcing and subjective effects.

Comer, Sandra D.; Sullivan, Maria A.; Walker, Ellen A.

2013-01-01

220

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

PubMed

Objective-To determine the pharmacokinetics of buprenorphine hydrochloride after IM and IV administration to American kestrels (Falco sparverius). Animals-13 healthy 3-year-old captive-bred American kestrels. Procedures-Buprenorphine hydrochloride (0.6 mg/kg) was administered IM to all birds. Blood samples were collected at 9 times, ranging from 5 minutes to 9 hours after drug administration. Plasma buprenorphine concentrations were measured by use of tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined by use of least squares linear regression and noncompartmental analysis of naïve pooled data. After a washout period of 2 weeks, the same dose of buprenorphine was administered IV to all birds and blood samples were collected at the same times after drug administration. Results-Maximum plasma buprenorphine concentration was achieved within 5 minutes after IM administration. For IM administration, bioavailability was 94.8% and elimination half-life was 92.1 minutes. For IV administration, steady-state volume of distribution was 4,023.8 mL/kg, plasma clearance was 49.2 mL/min/kg, and elimination half-life was 105.5 minutes. 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. PMID:25061701

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

2014-08-01

221

Buprenorphine as a safe alternative to methadone in a patient with acquired long QT syndrome: a case report.  

PubMed

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

de Jong, I M; de Ruiter, G S

2013-05-01

222

[Modern surgical treatment of aneurysmal bone cyst using a synthetic bone substitute (Ceraform, a calcium phosphate ceramic)].  

PubMed

Aneurysmal bone cyst is a benign pseudotumoral dystrophy of bone, presenting expansive, destructive, nonresolutive features and often recurrence. A "stand-by" therapeutically attitude, in a survey manner, based on some spontaneous regression of certain areas of the aneurysmal cyst, due to thrombosis and fibrosis, is rarely advocated. When tumoral lesions are located in long bones and the bone length must be preserved, the bioptic curettage, followed or not by auto-grafting or cortical/cancellous allografting to bridge defect, represents the treatment of choice. The inconveniences encountered in using auto- or allografts have raised a growing interest towards synthetic bone substitutes. The most used of them are phosphocalcic ceramics due to their basic properties regarding interaction between bone and the substitution material, especially macroporosity Lately, we started to use (as clinical application) a bone substitute based on synthetic biphasic macroporous ceramic (CERAFORM), covering a wide range of procedures: benign tumors and dystrophies, spinal or joint arthrodesis, periprosthetic fractures, revisions following failures of primary total hip replacements. We obtained promising results, suggesting that in a situation with limited bone defects, as in clinical case presentation, if there exist a good contact and strong mechanical fixation, CERAFORM represents a reliable option comparing to allograft. PMID:14756045

Botez, P

2003-01-01

223

Methadone- and buprenorphine-related ambulance attendances: a population-based indicator of adverse events.  

PubMed

This study examined the nature and extent of methadone- and buprenorphine-related morbidity through a retrospective analysis of ambulance service records (N = 243) in Melbourne, Australia. Cases in which methadone and buprenorphine were implicated are examined. Demographic and presenting characteristics, transport outcomes, and other substance use were explored. There were 84 buprenorphine-related attendances and 159 methadone-related attendances recorded on the database over the 4-year period. Presenting signs (respiratory rate and Glasgow Coma Scale score) were lower in the methadone-related attendances. Most of the attendances resulted in transport to hospital. Most presentations did not involve traditional signs of opioid overdose, a finding that warrants further investigation. This is the first article to describe characteristics of methadone- and buprenorphine-related ambulance attendances, with results suggesting this may be a useful way to monitor harms associated with these medications in the future. PMID:18295435

Nielsen, Suzanne; Dietze, Paul; Cantwell, Kate; Lee, Nicole; Taylor, David

2008-12-01

224

Evaluation of the perioperative analgesic efficacy of buprenorphine, compared with butorphanol, in cats.  

PubMed

Objective-To compare the analgesic effects of buprenorphine and butorphanol in domestic cats. Design-2-phase positive-controlled randomized masked clinical trial. Animals-39 healthy female cats (10 in phase 1 and 29 in phase 2). Procedures-Cats admitted for ovariohysterectomy received buprenorphine (4 in phase 1; 14 in phase 2) or butorphanol (6 in phase 1; 15 in phase 2). In phase 1, cats were premedicated with buprenorphine (0.02 mg/kg [0.009 mg/lb], IM) or butorphanol (0.4 mg/kg [0.18 mg/lb], IM), in combination with medetomidine. Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. After extubation, medetomidine was antagonized with atipamezole. A validated multidimensional composite scale was used to assess signs of pain after surgery starting 20 minutes after extubation and continuing for up to 360 minutes, and pain score comparisons were made between the 2 groups. Phase 2 proceeded similar to phase 1 with the following addition: during wound closure, cats from the butorphanol and buprenorphine groups received butorphanol (0.4 mg/kg, IM) or buprenorphine (0.02 mg/kg, IM), respectively. Results-Phase 1 of the study was stopped after 10 cats were ovariohysterectomized because 9 of 10 cats required rescue analgesia at the first evaluation. In phase 2, at the first pain evaluation, pain scores from the buprenorphine group were lower, and all cats from the butorphanol group required rescue analgesia. None of the cats from the buprenorphine group required rescue analgesia at any time. Conclusions and Clinical Relevance-Buprenorphine (0.02 mg/kg, IM) given before surgery and during wound closure provided adequate analgesia for 6 hours following ovariohysterectomy in cats, whereas butorphanol did not. PMID:24984130

Warne, Leon N; Beths, Thierry; Holm, Merete; Carter, Jennifer E; Bauquier, Sébastien H

2014-07-15

225

Successful transition to buprenorphine in a patient with methadone-induced torsades de pointes.  

PubMed

A 56-year-old-man presented with syncope and torsades de pointes secondary to methadone-induced QT prolongation. After transition from methadone to buprenorphine, a partial mu-opiate-receptor agonist and a kappa-opiate-receptor antagonist, the QT normalized and ventricular arrhythmias resolved. Buprenorphine should be used for opiate dependence and chronic pain in patients with methadone-induced QT prolongation and as first line therapy in patients with risk factors for torsades de pointes. PMID:18686025

Esses, Jason Levi; Rosman, Jonathan; Do, Lien Thanh; Schweitzer, Paul; Hanon, Sam

2008-11-01

226

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

PubMed Central

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.

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

2011-01-01

227

Analysis of buprenorphine in whole blood using liquid chromatography-tandem mass spectrometry.  

PubMed

With buprenorphine use on the rise it has become more important than ever for the forensic laboratory to be capable of analyzing for it. Described is the approach used by the Georgia Bureau of Investigation for the screening and confirmation of buprenorphine in whole blood by liquid chromatography-tandem mass spectrometry (LC-MS-MS), along with case reviews for the first 2 months of method implementation. Screening by LC-MS-MS is capable of identifying buprenorphine cases at concentrations as low as 1-2 µg/L. Confirmatory testing is performed on both indicatively screened samples and cases where buprenorphine is specifically requested. Confirmatory analysis by LC-MS-MS has a limit of detection and limit of quantitation of 0.75 µg/L with estimated uncertainties of 7.2% at 1 µg/L, 3.5% at 10 µg/L and 4.8% at 20 µg/L based on a 95% confidence interval, with the highest percent coefficient of variation being 3.7% for the 1 µg/L level. Since its implementation, the laboratory has reported out nine cases for buprenorphine. Seven of those cases were detected by the initial screen and two were identified by a specific request for buprenorphine. The cases' average concentration was 4.25 µg/L with a mode of 3.1 µg/L. PMID:23983012

Stephenson, Jon B

2013-10-01

228

Tolerance to the mydriatic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine in mice.  

PubMed

An increase in the use of opioid derivatives in the treatment of pain syndrome in clinical practice, and especially in the treatment of cancer, has added impetus to the search for an agent which does not induce tolerance and cross-tolerance to other opiodis. The mydriatic effect of opioids in mice, the correlation between analgesia and mydriasis, and tolerance to the analgesic effect of morphine in mice were evaluated previously. In the present work, tolerance to the mydriatic effect of four agonist-antagonists and cross-tolerance to morphine were examined. Measurement of the pupillary diameter was performed using a binocular operating microscope. Tolerance and cross-tolerance to morphine were developed following a chronic use of buprenorphine, nalbuphine, and cyclorphan. After chronic injection of butorphanol, no tolerance or cross-tolerance to morphine was observed. PMID:23568116

Kaadan, M; Stav, A; Rabinowitz, R; Shavit, S; Korczyn, A D

1994-09-01

229

Barriers and facilitators for assessment and treatment of hepatitis C virus infection in the opioid substitution treatment setting: insights from the ETHOS study.  

PubMed

Provision of hepatitis C virus (HCV) assessment and treatment via opioid substitution treatment (OST) clinics has been posed as an effective means of engaging populations with high HCV prevalence. This study explores OST client and health professional reports concerning barriers and facilitators affecting the delivery and uptake of HCV care and treatment within OST settings. In-depth interviews were conducted with 57 clients, 16 staff from four NSW clinics participating in the Australian ETHOS study and three peer workers. Client participants included those who had not had HCV assessment; those who had HCV assessment only; and those who were awaiting or undertaking HCV treatment. A clear difference in decisions about HCV treatment emerged between participant groups. For those who have not been assessed, barriers to engaging with HCV care included the perception that they were physically well, were not experiencing HCV symptoms, had other life priorities and were concerned about the side effects and tolerability of treatment. Those who had engaged with care expressed motivations stemming from seeing friends becoming unwell, wanting to live longer and hearing positive stories of treatment. For those interested in HCV treatment, issues related to both provider and setting were important, such as presence of an engaged clinician, an accessible treatment pathway and availability of support. In this integrated care model, some barriers to HCV care and treatment (particularly those relating to health provider and the system) are minimized. In this setting, HCV treatment remained an unattractive option for a significant number of clients. Providing ways for those without HCV symptoms to be assessed for liver damage may be important to open up alternative conversations about HCV care. Further, the importance of a changing discourse of treatment is apparent from these data and could be enhanced by peer communication that provides information about successful treatment experiences. PMID:24299222

Treloar, C; Rance, J; Dore, G J; Grebely, J

2014-08-01

230

Improving Adherence to HIV Quality of Care Indicators in Persons With Opioid Dependence: The Role of Buprenorphine  

PubMed Central

Background Opioid-dependent HIV-infected patients are less likely to receive HIV quality of care indicators (QIs) compared with nondependent patients. Buprenorphine/naloxone maintenance therapy (bup/nx) could affect the quality of HIV care for opioid-dependent patients. Methods We abstracted 16 QIs from medical records at nine HIV clinics 12 months before and after initiation of bup/nx versus other treatment for opioid dependence. Summary quality scores (number of QIs received/number eligible × 100) were calculated. We compared change in QIs and summary quality scores in patients receiving bup/nx versus other participants. Results One hundred ninety-four of 268 participants (72%) received bup/nx and 74 (28%) received other treatment. Mean summary quality scores increased over 12 months for participants receiving bup/nx (45.6% to 51.6%, P < 0.001) but not other treatment (48.6% to 47.8%, P = 0.788). Bup/nx participants experienced improvements in six of 16 HIV QIs versus three of 16 QIs in other participants. Improvements were mostly in preventive and monitoring care domains. In multivariable analysis, bup/nx was associated with improved summary quality score (? 8.55; 95% confidence interval, 2.06–15.0). Conclusions In this observational cohort study, HIV-infected patients with opioid dependence received approximately half of HIV QIs at baseline. Buprenorphine treatment was associated with improvement in HIV QIs at 12 months. Integration of bup/nx into HIV clinics may increase receipt of high-quality HIV care. Further research is required to assess the effect of improved quality of HIV care on clinical outcomes.

Korthuis, P. Todd; Fiellin, David A.; Fu, Rongwei; Lum, Paula J.; Altice, Frederick L.; Sohler, Nancy; Tozzi, Mary J.; Asch, Steven M.; Botsko, Michael; Fishl, Margaret; Flanigan, Timothy P.; Boverman, Joshua; McCarty, Dennis

2011-01-01

231

A Clinical Trial Comparing Tapering Doses of Buprenorphine with Steady Doses for Chronic Pain and Co-existent Opioid Addiction  

PubMed Central

Objectives Effective strategies are needed to manage individuals with chronic non-cancer pain and coexistent opioid addiction. This study compared opioid discontinuation and opioid replacement protocols. Methods We planned to enroll 60 individuals into an open-label trial who had been treated with opioids for chronic non-cancer pain, and who also had opioid addiction. Participants were randomly assigned to one of two 6-month treatment protocols of buprenorphine/naloxone sublingual tablets: 1) tapering doses for opioid weaning or “detoxification” (active comparator group) or 2) steady doses for opioid replacement (experimental group). They were followed monthly for the study outcomes: completion of the 6-month treatment protocol and self-reported pain control, physical functioning, alcohol consumption and illicit drug use. Results Enrollment was terminated after enrolling 12 participants because none of the 6 assigned to receive tapering doses could successfully complete the protocol (5 were given steady doses and 1 was admitted to an inpatient chemical dependency treatment program); whereas, of the 6 assigned to receive steady doses, 5 completed the protocol (1 withdrew). This difference between the 2 treatment conditions was significant (P = 0.015). Of the 10 participants who completed the 6 month follow-up, 8 reported improved pain control and physical functioning and 5 used alcohol and/or illicit drugs. Conclusions We conclude that over 6 months, these participants with chronic pain and co-existent opioid addiction were more likely to adhere to an opioid replacement protocol than an opioid weaning protocol and that opioid replacement therapy with steady doses of buprenorphine/naloxone is associated with improved pain control and physical functioning.

Blondell, Richard D.; Ashrafioun, Lisham; Dambra, Christina M.; Foschio, Elisa M.; Zielinski, Amy L.; Salcedo, Daniel M.

2009-01-01

232

On drug treatment and social control: Russian narcology's great leap backwards  

PubMed Central

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 totally unsupported by scientific evidence and inquiry, officials in Russia have rendered narcology ( and medical practice) insensitive to the alarming rates and continued spread of HIV, with its dire morbidity and mortality rates in the Russian Federation, turning their backs on all the other health problems posed by opiate use and dependence itself.

Elovich, Richard; Drucker, Ernest

2008-01-01

233

Patterns of free (unconjugated) buprenorphine, norbuprenorphine, and their glucuronides in urine using liquid chromatography-tandem mass spectrometry.  

PubMed

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

McMillin, Gwendolyn A; Davis, Rebecka; Carlisle, Heidi; Clark, Chantry; Marin, Stephanie J; Moody, David E

2012-03-01

234

Production and validation of model iron-tannate dyed textiles for use as historic textile substitutes in stabilisation treatment studies  

PubMed Central

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.

2012-01-01

235

Buprenorphine/Naloxone and Methadone Effects on Laboratory Indices of Liver Health: a Randomized Trial  

PubMed Central

BACKGROUND Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants. METHODS This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met “evaluable” criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified. RESULTS Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants. CONCLUSIONS This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury.

Saxon, Andrew J.; Ling, Walter; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Ang, Alfonso; Doraimani, Geetha; Tasissa, Gudaye; Lokhnygina, Yuliya; Leimberger, Jeff; Bruce, R. Douglas; McCarthy, John; Wiest, Katharina; McLaughlin, Paul; Bilangi, Richard; Cohen, Allan; Woody, George; Jacobs, Petra

2012-01-01

236

A dose–effect study of repeated administration of buprenorphine\\/naloxone on performance in opioid-dependent volunteers  

Microsoft Academic Search

Based on its unique pharmacological profile, buprenorphine may produce less impairment in psychomotor and cognitive performance than methadone. However, the few studies that have investigated the performance effects of buprenorphine in opioid-abusing volunteers examined effects of single acute doses rather than effects of repeated dosing and included a very limited range of measures. The present inpatient study evaluated dose-related effects

Miriam Z. Mintzer; Christopher J. Correia; Eric C. Strain

2004-01-01

237

Drug interactions associated with methadone, buprenorphine, cocaine, and HIV medications: implications for pregnant women  

PubMed Central

Pregnancy in substance-abusing women with HIV/AIDS presents a complex clinical challenge. Opioid-dependent women need treatment with opioid therapy during pregnancy to protect the health of mother and developing fetus. However, opioid therapies, methadone and buprenorphine, may have drug interactions with some HIV medications that can have adverse effects leading to suboptimal clinical outcomes. Further, many opioid-dependent individuals have problems with other forms of substance abuse, for example, cocaine abuse, that could also contribute to poor clinical outcomes in a pregnant woman. Physiological changes, including increased plasma volume and increased hepatic and renal blood flow, occur in the pregnant woman as the pregnancy progresses and may alter medication needs with the potential to exacerbate drug interactions, although there is sparse literature on this issue. Knowledge of possible drug interactions between opioids, other abused substances such as cocaine, HIV therapeutics, and other frequently required medications such as antibiotics and anticonvulsants is important to assuring the best possible outcomes in the pregnant woman with opioid dependence and HIV/AIDS.

McCance-Katz, Elinore F.

2010-01-01

238

Drug interactions associated with methadone, buprenorphine, cocaine, and HIV medications: implications for pregnant women.  

PubMed

Pregnancy in substance-abusing women with HIV/AIDS presents a complex clinical challenge. Opioid-dependent women need treatment with opioid therapy during pregnancy to protect the health of mother and developing fetus. However, opioid therapies, methadone and buprenorphine, may have drug interactions with some HIV medications that can have adverse effects leading to suboptimal clinical outcomes. Further, many opioid-dependent individuals have problems with other forms of substance abuse, for example, cocaine abuse, that could also contribute to poor clinical outcomes in a pregnant woman. Physiological changes, including increased plasma volume and increased hepatic and renal blood flow, occur in the pregnant woman as the pregnancy progresses and may alter medication needs with the potential to exacerbate drug interactions, although there is sparse literature on this issue. Knowledge of possible drug interactions between opioids, other abused substances such as cocaine, HIV therapeutics, and other frequently required medications such as antibiotics and anticonvulsants is important to assuring the best possible outcomes in the pregnant woman with opioid dependence and HIV/AIDS. PMID:20965297

McCance-Katz, Elinore F

2011-05-23

239

Treatment of experimental osteomyelitis with antibiotic-impregnated bone graft substitute.  

PubMed

The model of Norden was used to induce osteomyelitis in the left tibia of New Zealand White rabbits. Twenty-one days following inoculation, the animals had primary debridement and then were randomized into one of three treatment groups. Group I received no additional treatment; in Group II, plain hydroxyapatite beads were packed into the defect; and in Group III, gentamicin crobefat-loaded hydroxyapatite beads were packed into the defect. The animals were observed for 40 days after the primary debridement and then were killed. The intensity of infection was determined by swab cultures and quantitative bacterial cultures of the debrided material. At primary debridement, all of the animals in each group were equally infected. At the time of secondary debridement, only the animals in Group III had a statistically significant reduction in infection (p < 0.001). In this study, we demonstrated that an antibiotic-loaded osteoinductive ceramic bead can effectively eliminate bacteria from an osteomyelitic cavity. PMID:8410460

Cornell, C N; Tyndall, D; Waller, S; Lane, J M; Brause, B D

1993-09-01

240

Sublingual Buprenorphine/Naloxone for Chronic Pain in At-Risk Patients: Development and Pilot Test of a Clinical Protocol  

PubMed Central

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 ?-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.

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

241

Development of sensitization to methamphetamine in offspring prenatally exposed to morphine, methadone and buprenorphine.  

PubMed

Heroin use among young women of reproductive age has drawn much attention around the world. However, there is lack of information on the long-term effects of prenatal exposure to opioids on their offspring. Our previous study demonstrated that prenatally buprenorphine-exposed offspring showed a marked change in the cross-tolerance to morphine compared with other groups. In the current study, this animal model was used to study effects of methamphetamine (METH)-induced behavioral sensitization in the offspring at their adulthood. The results showed no differences in either basal or acute METH-induced locomotor activity in any of the groups of animals tested. When male offspring received METH injections of 2?mg/kg, i.p., once a day for 5?days, behavioral sensitization was induced, as determined by motor activity. Furthermore, the distance and rate of development (slope) of locomotor activity and conditioned place preference induced by METH were significantly increased in the prenatally buprenorphine-exposed animals compared with those in other groups. The dopamine D1 R in the nucleus accumbens of the prenatally buprenorphine-exposed offspring had lower mRNA expression; but no significant changes in the ?-, ?-opioid, nociceptin, D2 R and D3 R receptors were noted. Furthermore, significant alterations were observed in the basal level of cAMP and the D1 R agonist enhanced adenylyl cyclase activity in the prenatally buprenorphine-exposed group. Overall, the study demonstrates that D1 R and its downregulated cAMP signals are involved in enhancing METH-induced behavioral sensitization in prenatally buprenorphine-exposed offspring. The study reveals that prenatal exposure to buprenorphine caused long-term effects on offspring and affected the dopaminergic system-related reward mechanism. PMID:23551991

Chiang, Yao-Chang; Hung, Tsai-Wei; Ho, Ing-Kang

2014-07-01

242

Buprederm™, a New Transdermal Delivery System of Buprenorphine: Pharmacokinetic, Efficacy and Skin Irritancy Studies  

Microsoft Academic Search

Purpose  The pharmacokinetics, analgesic efficacy, and irritancy potential of Buprederm™, a new transdermal delivery system of buprenorphine,\\u000a was evaluated.\\u000a \\u000a \\u000a \\u000a Methods  Single and multiple dose pharmacokinetic studies were conducted in mice and rabbits. The analgesic efficacy and skin irritation\\u000a potential were determined by tail flick and writhing tests in mice and by the Draize dermal scoring system in rabbits.\\u000a \\u000a \\u000a \\u000a Results  Fast absorption of buprenorphine

Dongwon Kim; Jindeog Song; Chang Hoon In; Seung-Wei Jeong; Sang Hun Lee; Bumchan Min; Dongho Lee; Sun-Ok Kim

2008-01-01

243

Illicit use of methadone and buprenorphine among adolescents and young adults in Sweden  

PubMed Central

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 young drug users is not a widespread problem in Sweden. Harm-reduction measures should target drug users with more severe problems, among whom illicit use of methadone and buprenorphine is more common and pose a medical risk. Illicit use of other prescription drugs, which are less controlled and more widely used by young people, is an important issue for further research.

2013-01-01

244

Human Split-Thickness Skin Allograft: Skin Substitute in the Treatment of Burn  

PubMed Central

Background: Human skin allograft has been used as wound coverage for a long time; it is one of the most successful and widely used dressings for burn wounds in the world. Objective: To prepare a freeze-dried human split-thickness skin allograft and evaluate its cytotoxicity, the structure and physical properties after processing methods and clinical efficacy in burn patients. Methods: After ensuring tissue safety, we lyophilized human cadaveric partial thickness skin and exposed it to gamma radiation. Histopathological and immunohistochemical properties, tensile strength and in vitro cytotoxicity were assayed for the skin samples. Then, we tested the samples in 11 patients with deep skin burn. Results: On histological and histopathological examinations, we found a normal skin structure. The tensile strength of the rehydrated freeze-dried human skin allograft was not lesser than the fresh human skin. Cell viability in MTT testing was more than 95%. None of our patients showed any signs of immunological reactions or complications. Conclusion: Gamma-irradiated freeze-dried human split-thickness skin is safe and non-toxic and can be used for the treatment of patients with deep skin burn.

Mahdavi-Mazdeh, M.; Nozary Heshmati, B.; Tavakoli, S. A. H.; Ayaz, M.; Azmoudeh Ardalan, F.; Momeni, M.

2013-01-01

245

Development of nanofibrous cellulose acetate/gelatin skin substitutes for variety wound treatment applications.  

PubMed

The major component of fibrous extracellular matrix of dermis is composed of a complex combination of proteins and polysaccharides. Electrospun cellulose acetate/gelatin might be an effective simulator of the structure and composition of native skin and during this study, we electrospun cellulose acetate/gelatin membranes in various compositions and their performance as a scaffold for either skin tissue engineering or as a wound dressing was evaluated. Skin treatment products, whether tissue-engineered scaffolds or wound dressings, should be sufficiently hydrophilic to allow for gas and fluid exchange and absorb excess exudates while controlling the fluid loss. However, a wound dressing should be easily removable without causing tissue damage and a tissue-engineered scaffold should be able to adhere to the wound, and support cell proliferation during skin regeneration. We showed that these distinct adherency features are feasible just by changing the composition of cellulose acetate and gelatin in composite cellulose acetate/gelatin scaffolds. High proliferation of human dermal fibroblasts on electrospun cellulose acetate/gelatin 25:75 confirmed the capability of cellulose acetate/gelatin 25:75 nanofibers as a tissue-engineered scaffold, while the electrospun cellulose acetate/gelatin 75:25 can be a potential low-adherent wound dressing. PMID:23640859

Vatankhah, Elham; Prabhakaran, Molamma P; Jin, Guorui; Mobarakeh, Laleh Ghasemi; Ramakrishna, Seeram

2014-02-01

246

Clinical relevance of substitutions in the connection subdomain and RNase H domains of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-na?ve patients  

PubMed Central

Some mutations in the connection subdomain of the polymerase domain and in the RNase H domain of HIV-1 reverse transcriptase (RT) have been shown to contribute to resistance to RT inhibitors. However, the clinical relevance of such mutations is not well understood. To address this point we determined the prevalence of such mutations in a cohort of antiretroviral treatment-naïve patients (n=123) and assessed whether these substitutions are associated with drug resistance in vitro and in vivo. We report here significant differences in the prevalence of substitutions among subtype B, and non-subtype B HIV isolates. Specifically, the E312Q, G333E, G335D, V365I, A371V and A376S substitutions were present in 2–6% of subtype B, whereas the G335D and A371V substitutions were commonly observed in 69 and 75% of non-B HIV-1 isolates. We observed a significant decline in the viral loads of patients that were infected with HIV-1 carrying these substitutions and were subsequently treated with triple drug regimens, even in the case where zidovudine (AZT) was included in such regimens. We show here that generally, such single substitutions at the connection subdomain or RNase H domain have no influence on drug susceptibility in vitro by themselves. Instead, they generally enhance AZT resistance in the presence of excision-enhancing mutations (EEMs, also known as thymidine analogue-associated mutations, TAMs). However, N348I, A376S and Q509L did confer varying amounts of nevirapine resistance by themselves, even in the absence of EEMs. Therefore, our cohort establishes that several connection subdomain and RNase H domain substitutions typically act as pre-therapy polymorphisms.

Hachiya, Atsuko; Shimane, Kazuki; Sarafianos, Stefan G.; Kodama, Eiichi N.; Sakagami, Yasuko; Negishi, Fujie; Koizumi, Hirokazu; Gatanaga, Hiroyuki; Matsuoka, Masao; Takiguchi, Masafumi; Oka, Shinichi

2012-01-01

247

Concomitant Use of Midazolam and Buprenorphine and its Implications Among Drug Users in Singapore  

Microsoft Academic Search

Introduction: The aim of this study was to determine the prevalence and characteristics of benzodiazepine (BZD) abuse among intravenous opioid users in Singapore. Materials and Methods: Eligibility criteria for inclusion in this study were all intravenous buprenorphine abusers, who presented to the Community Addictions Management Programme (CAMP) over a 1-year period from February 2005 to January 2006. One hundred and

Wei-Ling Ng; Subramaniam Mythily; Guo Song; Yiong-Huak Chan; Munidasa Winslow

248

Degradable Bone Graft Substitute for Effective Delivery of Multiple Growth Factors in the Treatment of Nonunion Fractures.  

National Technical Information Service (NTIS)

Our hypothesis was that a degradable, thermally-responsive bone graft substitute, made from renewable sources, that effectively and simultaneously delivers osteogenic and angiogenic growth factors directly to the bone defect site can enhance repair of non...

J. Bush

2012-01-01

249

Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats, and effects on thermal threshold.  

PubMed

This study reports the pharmacokinetics of buprenorphine, following i.v. and buccal administration, and the relationship between buprenorphine concentration and its effect on thermal threshold. Buprenorphine (20 ?g/kg) was administered intravenously or buccally to six cats. Thermal threshold was determined, and arterial blood sampled prior to, and at various times up to 24 h following drug administration. Plasma buprenorphine concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to the time-concentration data. Pharmacokinetic/pharmacodynamic models were fitted to the concentration-thermal threshold data. Thermal threshold was significantly higher than baseline 44 min after buccal administration, and 7, 24, and 104 min after i.v. administration. A two- and three-compartment model best fitted the data following buccal and i.v. administration, respectively. Following i.v. administration, mean ± SD volume of distribution at steady-state (L/kg), clearance (mL·min/kg), and terminal half-life (h) were 11.6 ± 8.5, 23.8 ± 3.5, and 9.8 ± 3.5. Following buccal administration, absorption half-life was 23.7 ± 9.1 min, and terminal half-life was 8.9 ± 4.9 h. An effect-compartment model with a simple effect maximum model best predicted the time-course of the effect of buprenorphine on thermal threshold. Median (range) ke0 and EC50 were 0.003 (0.002-0.018)/min and 0.599 (0.073-1.628) ng/mL (i.v.), and 0.017 (0.002-0.023)/min and 0.429 (0.144-0.556) ng/mL (buccal). PMID:24862514

Hedges, A R; Pypendop, B H; Shilo-Benjamini, Y; Stanley, S D; Ilkiw, J E

2014-06-01

250

The effects of prenatal exposure to buprenorphine or methadone on infant visual evoked potentials.  

PubMed

This study compared the neurological development of 4 month old infants exposed to buprenorphine or methadone during pregnancy to that of a control group of non-exposed infants. Participants were 30 buprenorphine-maintained women, 22 methadone-maintained women and 33 non opioid-dependent controls, and their infants. Women were enrolled during pregnancy as part of an open-label non-randomised flexible-dosing longitudinal study. Groups were matched for maternal age, parity, gravida, and tobacco and alcohol use. Infant neurological development was assessed by measuring latency of pattern reversal visual evoked potentials (VEP). 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). Infants prenatally exposed to methadone had significantly prolonged latencies, compared with infants in the control group and infants prenatally exposed to buprenorphine, in response to checks of 48' and 69'. VEP latencies of infants prenatally exposed to buprenorphine did not differ significantly from controls for either check size. After adjustment for covariates, prenatal exposure to methadone remained a significant predictor of VEP response to checks of 48', but not 69'. Maternal self-reported used of marijuana during pregnancy made a significant unique contribution to the variance in P1 latencies for both check sizes. Data from this controlled, non-randomised study suggest that buprenorphine may confer an advantage over methadone as a maintenance drug during pregnancy in terms of infant neural development at 4 months of age. PMID:19751825

Whitham, Justine N; Spurrier, Nicola J; Sawyer, Michael G; Baghurst, Peter A; Taplin, John E; White, Jason M; Gordon, Andrea L

2010-01-01

251

[Patient-controlled analgesia with epidural pethidine or buprenorphine plus bupivacaine for postoperative analgesia].  

PubMed

We evaluated the efficacy of epidural patient-controlled analgesia (PCA) with pethidine or buprenorphine plus 0.25% bupivacaine for postoperative analgesia after laparotomy with a midline incision under general anesthesia. Twenty patients were randomly allocated to two groups. In one group (PCEA-P group; n = 10), epidural pethidine plus 0.25% bupivacaine by PCA with 5 mg of pethidine and 2.5 ml of 0.25% bupivacaine bolus with a lockout interval of 20 min was added to a continuous epidural infusion of 0.25% bupivacaine (2 ml.h-1) plus pethidine (100 mg.24h-1) for 72 h. In the other group (PCEA-B group; n = 10), epidural buprenorphine plus 0.25% bupivacaine by PCA with 0.03 mg of buprenorphine and 2.5 ml of 0.25% bupivacaine bolus with a lockout interval of 20 min was added to a continuous epidural infusion of 0.25% bupivacaine (2 ml.h-1) and buprenorphine (0.6 mg.24 h-1) for 72 h. Analgesia was evaluated by 100 mm visual analog scale and verbal descriptor scale. In PCEA-B group, 90% of the patients did not complain of pain at rest, and in PCEA-P group, all the patients did not complain of pain at rest for 72 h. There were no significantly different analgesic effects between PCEA-P and PCEA-B for 48 h. The average doses of epidural PCA were 1.9 mg.kg-1.24 h-1 of pethidine, and 0.012 mg.kg-1.24 h-1 of buprenorphine, respectively. We conclude that PCEA-P and PCEA-B were effective for postoperative pain to the same degree for the first 48 h, but PCEA-P was superior to PCEA-B for the last 24 h. PMID:8254871

Mitsuhata, H; Hirabayashi, Y; Saitoh, K; Horiguchi, Y; Togashi, H; Shimizu, R; Hasegawa, J; Matsumoto, S

1993-11-01

252

Roles of ?-opioid receptors and nociceptin/orphanin FQ peptide receptors in buprenorphine-induced physiological responses in primates.  

PubMed

Buprenorphine is known as a ?-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 pK(B) 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 attenuate buprenorphine-induced antinociception in primates; instead, the coactivation of MOP and NOP receptors produced synergistic antinociception without other side effects. This study strongly supports the therapeutic potential of mixed MOP/NOP agonists as innovative analgesics. PMID:22743574

Cremeans, Colette M; Gruley, Erin; Kyle, Donald J; Ko, Mei-Chuan

2012-10-01

253

Roles of ?-Opioid Receptors and Nociceptin/Orphanin FQ Peptide Receptors in Buprenorphine-Induced Physiological Responses in Primates  

PubMed Central

Buprenorphine is known as a ?-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 attenuate buprenorphine-induced antinociception in primates; instead, the coactivation of MOP and NOP receptors produced synergistic antinociception without other side effects. This study strongly supports the therapeutic potential of mixed MOP/NOP agonists as innovative analgesics.

Cremeans, Colette M.; Gruley, Erin; Kyle, Donald J.

2012-01-01

254

Amino Acid Substitution in HCV Core\\/NS5A Region and Genetic Variation Near IL28B Gene Affect Treatment Efficacy to Interferon plus Ribavirin Combination Therapy  

Microsoft Academic Search

Objective: To evaluate predictive factors of treatment efficacy to interferon (IFN)\\/ribavirin in patients infected with HCV genotype 1b (HCV-1b). Methods: This study investigated pretreatment predictors, including viral- (aa substitutions in core aa 70\\/91 and NS5A-ISDR\\/IRRDR) and host-related factors (genetic variation near IL28B gene), to 48-week IFN\\/ribavirin in 490 Japanese adults infected with HCV-1b. Results: The proportion of patients who showed

Norio Akuta; Fumitaka Suzuki; Miharu Hirakawa; Yusuke Kawamura; Hitomi Sezaki; Yoshiyuki Suzuki; Tetsuya Hosaka; Masahiro Kobayashi; Mariko Kobayashi; Satoshi Saitoh; Yasuji Arase; Kenji Ikeda; Kazuaki Chayama; Yusuke Nakamura; Hiromitsu Kumada

2012-01-01

255

P-15 small peptide bone graft substitute in the treatment of non-unions and delayed union. A pilot clinical trial  

Microsoft Academic Search

Treatment of non-unions and delayed unions often requires osteogenic material. Recently, a biomimetic bone matrix that simulates\\u000a the cellular environment of hard tissue, identified as P-15, was introduced to the orthopaedic community. A total of 22 patients\\u000a with mal-union or delayed union fractures was treated from June 2000 to October 2003 with P15- bone graft substitute (P15-BGS)\\u000a in the site

Francisco Gomar; Rafael Orozco; Jose Luis Villar; Federico Arrizabalaga

2007-01-01

256

Compensatory substitutions in the HCV NS3/4A protease cleavage sites are not observed in patients treated unsuccessfully with telaprevir combination treatment  

PubMed Central

Background Development of compensatory mutations within the HIV p7/p1 and p1/p6 protease cleavage site region has been observed in HIV-infected patients treated with protease inhibitors. Mechanisms of fitness compensation may occur in HCV populations upon treatment of HCV protease inhibitors as well. Findings In this study, we investigated whether substitutions in protease cleavage site regions of HCV occur in response to a treatment regimen containing the NS3/4A protease inhibitor telaprevir (TVR). Evaluation of viral populations from 569 patients prior to treatment showed that the four NS3/4A cleavage sites were well conserved. Few changes in the cleavage site regions were observed in the 159 patients who failed TVR combination treatment, and no residues displayed evidence of directional selection after the acquisition of TVR-resistance. Conclusions Cleavage site mutations did not occur after treatment with the HCV protease inhibitor telaprevir.

2012-01-01

257

Italy's electronic health record system for opioid agonist treatment.  

PubMed

Electronic health record systems (EHRs) play an increasingly important role in opioid agonist treatment. In Italy, an EHR called the Multi Functional Platform (MFP) is in use in 150 opioid-agonist treatment facilities in 8 of Italy's 23 regions. This report describes MFP and presents 2010 data from 65 sites that treated 8145 patients, of whom 72.3% were treated with methadone and 27.7% with buprenorphine. Patients treated with buprenorphine compared to methadone were more likely to be male (p < .01) and younger (p < .001). Methadone compared to buprenorphine patients had a higher percentage of opioid-positive urine tests (p < .001) and longer mean length of stay (p = .004). MFP has been implemented widely in Italy and has been able to track patient outcomes across treatment facilities. In the future, this EHR system can be used for performance improvement initiatives. PMID:23518287

Serpelloni, Giovanni; Gomma, Maurizio; Genetti, Bruno; Zermiani, Monica; Rimondo, Claudia; Mollica, Roberto; Gryczynski, Jan; O'Grady, Kevin E; Schwartz, Robert P

2013-08-01

258

Buprenorphine 5, 10 and 20??g/h transdermal patch: a review of its use in the management of chronic non-malignant pain.  

PubMed

This article reviews the pharmacology, therapeutic efficacy and tolerability profile of the 7-day lower-dose (5, 10 and 20??g/h) buprenorphine transdermal patch (BuTrans®, Norspan®) in the management of chronic non-malignant pain, with a focus on European labelling for the drug. Buprenorphine is a semi-synthetic opioid analgesic that acts primarily as a partial agonist at the mu opioid receptor. The transdermal formulation provides continuous delivery of buprenorphine, resulting in relatively consistent plasma drug concentrations throughout the 7-day dosing interval. The analgesic efficacy of transdermal buprenorphine in patients with osteoarthritis of the hip and/or knee has been demonstrated in several randomized controlled trials, which have shown the formulation to be equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol tablets, noninferior to codeine plus paracetamol (acetaminophen) combination tablets (when transdermal buprenorphine was used together with regularly scheduled oral paracetamol) and generally superior to a matching transdermal placebo patch. Transdermal buprenorphine was significantly more effective than placebo in reducing chronic low back pain of at least moderate severity in two randomized, double-blind, crossover trials. Other clinical trials, including a randomized, double-blind, maintenance-of-analgesia study, have also demonstrated the analgesic efficacy of transdermal buprenorphine in patients with chronic non-malignant pain of various causes. In general, serious adverse events with transdermal buprenorphine are similar to those for other opioid analgesics. Transdermal buprenorphine has a ceiling effect for respiratory depression, and the main risk is when it is combined with other CNS depressants. The most frequently reported adverse events with transdermal buprenorphine are headache, dizziness, somnolence, constipation, dry mouth, nausea, vomiting, pruritus, erythema, application site pruritus and application site reactions. Transdermal buprenorphine was better tolerated than sublingual buprenorphine in a 7-week, randomized, double-blind trial in patients with osteoarthritis pain. Nevertheless, as with other opioids, persistence with transdermal buprenorphine therapy is difficult for many patients because of adverse events or other reasons. Thus, transdermal buprenorphine has generally demonstrated good efficacy and tolerability in clinical trials in chronic non-malignant pain, providing effective background analgesia as part of pain management strategies for patients with osteoarthritis, low back pain and other persistent pain syndromes of at least moderate severity. It also has favourable pharmacodynamic and pharmacokinetic properties, which have beneficial clinical implications, most notably the convenience of once-weekly administration and no need for dosage adjustments in the elderly or those with compromised renal function, making it an opioid of choice in these patients, and a useful therapeutic option overall in the management of chronic non-malignant pain. PMID:22141389

Plosker, Greg L

2011-12-24

259

Longitudinal missing data strategies for substance use clinical trials using generalized estimating equations: an example with a buprenorphine trial  

PubMed Central

Objective A review of substance use clinical trials indicates that sub-optimal methods are the most commonly used procedures to deal with longitudinal missing information. Methods Listwise deletion (i.e., using complete cases only), positive urine analysis (UA) imputation, and multiple imputation (MI) were used to evaluate the effect of baseline substance use and buprenorphine/naloxone tapering schedule (7 or 28 days) on the probability of a positive UA (UA+) across the 4-week treatment period. Results The listwise deletion generalized estimating equations (GEE) model demonstrated that those in the 28-day taper group were less likely to submit a UA+ for opioids during the treatment period (odds ratios (OR) = 0.57, 95% confidence interval (CI): 0.39–0.83), as did the positive UA imputation model (OR = 0.43, CI: 0.34–0.55). The MI model also demonstrated a similar effect of taper group (OR = 0.57, CI: 0.42–0.77), but the effect size was more similar to that of the listwise deletion model. Conclusions Future researchers may find utilization of the MI procedure in conjunction with the common method of GEE analysis as a helpful analytic approach when the missing at random assumption is justifiable.

McPherson, Sterling; Barbosa-Leiker, Celestina; McDonell, Michael; Howell, Donelle; Roll, John

2013-01-01

260

Comparison of the analgesic effects of robenacoxib, buprenorphine and their combination in cats after ovariohysterectomy.  

PubMed

The aim of this study was to compare the postoperative analgesic effects of robenacoxib and buprenorphine alone or in combination, in cats after ovariohysterectomy. Thirty healthy cats were randomly assigned to receive buprenorphine (0.02 mg/kg, n=10; GB), robenacoxib (2mg/kg, n=10; GR) or their combination at the same dosages (n=10; GBR) SC. After 30 min cats were sedated with an IM administration of medetomidine (0.02 mg/kg) and ketamine (5mg/kg). General anaesthesia was induced with propofol and after intubation was maintained with isoflurane. Before premedication and at 1, 2, 3, 4, 6, 8, 12 and 24h after extubation, pain and sedation were assessed using a simple descriptive pain scale, ranging from 0 (no pain/no sedation) to 4 (intense pain/ deep sedation). If the pain score was ? 3, rescue analgesia was provided using buprenorphine (0.02 mg/kg) administered IM. Pain score was higher in GB at 2, 3, 4, 6 and 8h compared to baseline and compared to GBR at the same study times. Moreover, the pain score was also higher in GB compared to GR at 2, 3, 4 and 6h. Pain score was similar at all study times between GR and GBR. Sedation at 1 and 2h was higher than baseline values in all groups. Cats in GB received rescue analgesia more often than cats assigned to GR or GBR. Robenacoxib was an effective analgesic drug in cats up to 24h after ovariohysterectomy. The addition of buprenorphine did not provide any additional analgesic effects compared to robenacoxib alone. PMID:23434263

Staffieri, F; Centonze, P; Gigante, G; De Pietro, L; Crovace, A

2013-08-01

261

Short communication A dose-effect study of repeated administration of buprenorphine\\/naloxone on performance in opioid-dependent volunteers  

Microsoft Academic Search

Based on its unique pharmacological profile, buprenorphine may produce less impairment in psychomotor and cognitive performance than methadone. However, the few studies that have investigated the performance effects of buprenorphine in opioid-abusing volunteers examined effects of single acute doses rather than effects of repeated dosing and included a very limited range of measures. The present inpatient study evaluated dose-related effects

Miriam Z. Mintzer; Christopher J. Correia; Eric C. Strain

262

Postoperative analgesic effects of dexketoprofen, buprenorphine and tramadol in dogs undergoing ovariohysterectomy.  

PubMed

The objective of this study was to compare the postoperative analgesic effects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02 mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48 h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy. PMID:23562407

Morgaz, J; Navarrete, R; Muñoz-Rascón, P; Domínguez, J M; Fernández-Sarmiento, J A; Gómez-Villamandos, R J; Granados, M M

2013-08-01

263

Changes in thyroid function tests induced by 2 month carbamazepine treatment in l-thyroxine-substituted hypothyroid children  

Microsoft Academic Search

In five l-thyroxine-substituted hypothyroid children with partial epilepsy serum total thyroxine (T4) and free T4 (FT4) significantly (P3, FT3) were not observed; consequently T3:T4 and FT3:FT4 ratios significantly (P4 decrease. The negligible thyroid hormone secretion and the unmodified T3-uptake (T3U) or T4-binding globulin (TBG) exclude direct effects of CBZ on thyroid gland and on carrier serum proteins, respectively. The findings

F. De Luca; T. Arrigo; E. Pandullo; M. F. Siracusano; S. Benvenga; F. Trimarchi

1986-01-01

264

Post-synthesis treatment gives highly stable siliceous zeolites through the isomorphous substitution of silicon for germanium in germanosilicates.  

PubMed

Germanosilicates, an important family of zeolites with increasing number of members and attractive porosities, but containing a large quantity of unstable Ge atoms in the framework, meet with great obstacles in terms of limited thermal and hydrothermal stability when it comes to practical use. A facile stabilization method thus has been developed to substitute isomorphously Ge atoms for Si atoms, giving rise to ultrastable siliceous analogues of the pristine germanosilicates. PMID:24375782

Xu, Hao; Jiang, Jin-Gang; Yang, Boting; Zhang, Lin; He, Mingyuan; Wu, Peng

2014-01-27

265

Blood Substitutes.  

National Technical Information Service (NTIS)

The functional characteristics of heme proteins can be modified to produce hemoglobins that can be used as blood substitutes in different therapeutic applications. Stable polymers of tetrameric hemoglobin, and of myoglobin molecules, are provided for use ...

C. Fronticelli W. S. Brinigar

2004-01-01

266

Aspirin Substitutes.  

National Technical Information Service (NTIS)

The research investigates the toxicity of the aspirin substitutes acetaminophen, phenacetin, and salicylamide. Fatalities, particularly in children, occur at relatively low doses of acetaminophen, due principally to hepatic necrosis, and also at relativel...

D. Neff J. T. Maddock K. Druck

1977-01-01

267

Buprenorphine 5, 10 and 20??g/h transdermal patch: a guide to its use in chronic non-malignant pain.  

PubMed

Buprenorphine lower-dose (5, 10 and 20??g/h) transdermal patches, which are administered once every 7 days, are indicated in the management of chronic non-malignant pain. This review focuses on the labelling of this formulation (BuTrans®) in the EU. The analgesic efficacy of transdermal buprenorphine in patients with osteoarthritis of the hip and/or knee has been demonstrated to be equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol and generally superior to a matching transdermal placebo patch. When used together with regularly scheduled oral paracetamol (acetaminophen), transdermal buprenorphine was noninferior to codeine plus paracetamol. Transdermal buprenorphine has also shown analgesic efficacy in patients with chronic non-malignant pain of various causes. PMID:22369187

Plosker, Greg L; Lyseng-Williamson, Katherine A

2012-04-01

268

Overview of Opioid Treatment Programs within the United States: 2008.  

National Technical Information Service (NTIS)

Various therapies are used in the treatment of substance abuse. One type of therapy used in the treatment of heroin or other opiate (narcotic) addiction is medication-assisted opioid therapy with medications such as methadone1 or buprenorphine. In order f...

2010-01-01

269

A call for evidence-based medical treatment of opioid dependence in the United States and Canada.  

PubMed

Despite decades of experience treating heroin or prescription opioid dependence with methadone or buprenorphine--two forms of opioid substitution therapy--gaps remain between current practices and evidence-based standards in both Canada and the United States. This is largely because of regulatory constraints and pervasive suboptimal clinical practices. Fewer than 10 percent of all people dependent on opioids in the United States are receiving substitution treatment, although the proportion may increase with expanded health insurance coverage as a result of the Affordable Care Act. In light of the accumulated evidence, we recommend eliminating restrictions on office-based methadone prescribing in the United States; reducing financial barriers to treatment, such as varying levels of copayment in Canada and the United States; reducing reliance on less effective and potentially unsafe opioid detoxification; and evaluating and creating mechanisms to integrate emerging treatments. Taking these steps can greatly reduce the harms of opioid dependence by maximizing the individual and public health benefits of treatment. PMID:23918492

Nosyk, Bohdan; Anglin, M Douglas; Brissette, Suzanne; Kerr, Thomas; Marsh, David C; Schackman, Bruce R; Wood, Evan; Montaner, Julio S G

2013-08-01

270

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

PubMed

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. PMID:18668369

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

2010-01-01

271

Potentials of ion trap collisional spectrometry for liquid chromatography/electrospray ionization tandem mass spectrometry determination of buprenorphine and nor-buprenorphine in urine, blood and hair samples.  

PubMed

A liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method has been developed for the analysis of buprenorphine (BUP) and nor-buprenorphine (NBUP) in biological fluids. Analytes are isolated from urine and blood, after addition of d4-buprenorphine (d4-BUP) as internal standard, by solid-phase extraction. Preparation of hair involves external decontamination, mechanical pulverization, overnight incubation in acidic medium, and neutralization prior to extraction. Enzymatic hydrolysis with beta-glucuronidase may be performed to distinguish between free and total BUP. Chromatographic separation is accomplished by gradient elution on a cyanopropyl 2.1 x 150 mm column. Positive ion ESI and MS analyses are carried out in an ion trap mass spectrometer. The use of this mass analyzer allows effective collisional experiments to be performed on ESI-generated MH+ species. Abundant product ions are produced, which can be monitored together with precursor ions without losing sensitivity. Thus, assay selectivity is definitely increased with respect to LC/ESI-MS/MS methods in which only precursor ions are monitored. The method has good linearity (calibration curves were linear in the range 0.1-10 ng/mL in urine and blood, in the range 10-160 pg/mg in hair) and limits of detection of 0.05 ng/mL for both BUP and NBUP in blood and urine samples, of 4 pg/mg for both analytes in hair. Both intra- and inter-assay precision and accuracy were satisfactory at three concentrations studied: relative standard deviations were <13.7% in urine, <17.3% in blood, <17.8% in hair; percent deviation of the mean from the true value was always <10.5% in urine and blood, <16.1% in hair. The method can be used to determine both analytes in the urine and hair of drug addicts on replacement therapy, and in post-mortem blood specimens when there is suspicion of drug-related death. PMID:16550495

Favretto, Donata; Frison, Giampietro; Vogliardi, Susanna; Ferrara, Santo Davide

2006-01-01

272

Monoalphabetic Substitution  

NSDL National Science Digital Library

This applet, created by Kevin O'Bryant of the University of California - San Diego, illustrates the monoalphabetic substitution codebreaking process using a chi-squared process. The author explains how and why this encryption method is used. Overall, it is a wonderful example of how probability and statistics can be applied to real world situations.

O\\'Bryant, Kevin

2009-12-09

273

Post operative analgesia after incisional infiltration of bupivacaine v/s bupivacaine with buprenorphine  

PubMed Central

Introduction: Opioid receptors have been demonstrated in the peripheral nerve endings of afferent neurons. Blockade of these receptors with peripherally administered opioid is believed to result in analgesia. Aim: To evaluate whether buprenorphine added to bupivacaine for wound infiltration can enhance post-operative analgesia via peripheral mechanisms. Materials and Methods: Forty ASA I and II adult patients scheduled for open donor nephrectomy were enrolled in this randomized double blind prospective study. In group A (n = 20) patients, the wound was infiltrated with bupivacaine 0.5% (2 mg/kg) and in group B (n = 20) with bupivacaine 0.5% (2 mg/kg) and buprenorphine (2 ?g/kg). All patients were given diclofenac 75 mg IM at 8 h interval. Post-operative quality of analgesia was assessed by VAS (0-10) for 24 h and when VAS > 4 rescue analgesic was administered. Total dose of rescue analgesic and side effects were noted. Results: The time of administration of first rescue analgesic was significantly higher in group B (10.52±5.54 h) as compared to group A (3.275±1.8 h). Mean VAS was significantly lower in group B as compared to group A. The total dosage of rescue analgesic was more in group A as compared to group B patients. Conclusion: Addition of buprenorphine to the local anesthetic significantly prolonged the time to first rescue analgesic requirement and the total consumption of rescue analgesic in 24 h, thus providing evidence in support of the existence of peripheral opioid receptors.

Mehta, Tanu R; Parikh, Beena K; Bhosale, Guruprasad P; Butala, Bina P; Shah, Veena R

2011-01-01

274

Comparison of intrathecal dexmedetomidine with buprenorphine as adjuvant to bupivacaine in spinal asnaesthesia.  

PubMed

Background: The supplementation of local anaesthetics with adjuvants to improve the efficacy of subarachnoid block has been recognised since long. The most preferred drug has been opioids, but newer drugs like dexmedetomidine has also been introduced and investigated as an effective adjuvant. Aim: This study was conducted to evaluate and compare the characteristics of subarachnoid blockade, hemodynamic stability and adverse effects of intrathecal buprenorphine and intrathecal dexmedetomidine as an adjuvant to 0.5% hyperbaric bupivacaine for lower abdominal surgeries. Materials and Methods: The present study included 60 patients aged between 18-60 years classified as American Society of Anesthesiologists (ASA) Physical Status (PS) I/II scheduled for elective lower abdominal surgeries. The patients were randomly allotted to two groups to receive intrathecal 3ml of 0.5% bupivacine with 60µg of buprenorphine (Group B; n=30) or 3ml of 0.5% bupivacaine with 5µg of dexmedetomidine (Group D; n=30). The onset time to peak sensory level, motor block, sedation, Haemodynamic variables, duration of motor block, analgesia and any adverse effects were noted. Results: There was no significant difference between groups regarding demographic characteristics and type of surgery. The motor, sensory blockade and time of rescue analgesia were significantly prolonged in Group D compared to Group B. The sedation level was higher in Group D compared to Group B. There was no significant difference in haemodynamic variables although Group B had lower Heart Rate (HR) than Group D. Conclusion: Intrathecal dexmedetomidine when compared to intrathecal buprenorphine causes prolonged anaesthesia and analgesia with reduced need for sedation and rescue analgesics. PMID:24701498

Gupta, Mahima; Shailaja, S; Hegde, K Sudhir

2014-02-01

275

Comparison of Intrathecal Dexmedetomidine with Buprenorphine as Adjuvant to Bupivacaine in Spinal Asnaesthesia  

PubMed Central

Background: The supplementation of local anaesthetics with adjuvants to improve the efficacy of subarachnoid block has been recognised since long. The most preferred drug has been opioids, but newer drugs like dexmedetomidine has also been introduced and investigated as an effective adjuvant. Aim: This study was conducted to evaluate and compare the characteristics of subarachnoid blockade, hemodynamic stability and adverse effects of intrathecal buprenorphine and intrathecal dexmedetomidine as an adjuvant to 0.5% hyperbaric bupivacaine for lower abdominal surgeries. Materials and Methods: The present study included 60 patients aged between 18-60 years classified as American Society of Anesthesiologists (ASA) Physical Status (PS) I/II scheduled for elective lower abdominal surgeries. The patients were randomly allotted to two groups to receive intrathecal 3ml of 0.5% bupivacine with 60µg of buprenorphine (Group B; n=30) or 3ml of 0.5% bupivacaine with 5µg of dexmedetomidine (Group D; n=30). The onset time to peak sensory level, motor block, sedation, Haemodynamic variables, duration of motor block, analgesia and any adverse effects were noted. Results: There was no significant difference between groups regarding demographic characteristics and type of surgery. The motor, sensory blockade and time of rescue analgesia were significantly prolonged in Group D compared to Group B. The sedation level was higher in Group D compared to Group B. There was no significant difference in haemodynamic variables although Group B had lower Heart Rate (HR) than Group D. Conclusion: Intrathecal dexmedetomidine when compared to intrathecal buprenorphine causes prolonged anaesthesia and analgesia with reduced need for sedation and rescue analgesics.

Gupta, Mahima; Shailaja, S.; Hegde, K. Sudhir

2014-01-01

276

Confirmatory Analysis of Buprenorphine, Norbuprenorphine, and Glucuronide Metabolites in Plasma by LCMSMS. Application to Umbilical Cord Plasma from Buprenorphine-maintained Pregnant Women  

PubMed Central

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 2 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 0.1–50 ng/mL for BUP and BUP-Gluc, and 0.5–50 ng/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 71.1–87.1%, and process efficiencies 48.7–127.7%. All compounds showed ion enhancement, except BUP-Gluc that demonstrated ion suppression: variation between 10 different blank plasma specimens was <9.1%. In 6 umbilical cord plasma specimens from opioid-dependent pregnant women receiving 14–24 mg/day BUP, NBUP-Gluc was the predominant metabolite (29.8±7.6 ng/mL), with BUP-Gluc (4.6±4.8 ng/mL), NBUP (1.5±0.8 ng/mL) and BUP (0.4±0.2 ng/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.

Concheiro, Marta; Jones, Hendree; Johnson, Rolley E.; Shakleya, Diaa M.; Huestis, Marilyn A.

2009-01-01

277

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

PubMed Central

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.

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

2009-01-01

278

Evaluation of the Clearance of a Sublingual Buprenorphine Spray in the Beagle Dog Using Gamma Scintigraphy  

Microsoft Academic Search

Purpose  The aim of this study was to evaluate clearance from the buccal cavity and pharmacokinetic profiles of a sublingual spray\\u000a formulation in the dog, to assist in interpretation of future pharmacokinetic studies.\\u000a \\u000a \\u000a \\u000a Methods  Radiolabelled buprenorphine in a spray formulation (400 ?g\\/100 ?l in 30% ethanol) was administered sublingually to four beagle\\u000a dogs, and the residence in the oral cavity was determined using gamma

Fiona McInnes; Nicola Clear; Gerry James; Howard N. E. Stevens; Unai Vivanco; Michael Humphrey

2008-01-01

279

TASTE CONDITIONING EFFECTS OF BUPRENORPHINE IN MORPHINE-NAIVE AND MORPHINE-EXPERIENCED RATS  

Microsoft Academic Search

Male Sprague–Dawley rats were injected daily with saline (morphine-naive rats) or 20 mg kg?1morphine (morphine-experienced rats), starting 15 days before the experiment. Subsequent taste conditioning indicated that 0.1 mg kg?1buprenorphine significantly decreased 0.025% saccharin consumption in morphine-naive, but not in morphine-experienced rats. A 10 mg kg?1dose of morphine gave similar results, whiled-amphetamine (0.75 mg kg?1) was consistently aversive. It was

M. GAIARDI; C. GUBELLINI; M. BARTOLETTI

1998-01-01

280

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

PubMed

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. PMID:24821206

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

2014-07-01

281

Use of mineralized collagen bone graft substitutes and dorsal locking plate in treatment of elder metaphyseal comminuted distal radius fracture  

NASA Astrophysics Data System (ADS)

Bone graft may be needed to fill bone defect in elderly patients with a metaphyseal comminuted distal radius fracture. In this retrospective, nonrandomized, single-surgeon study, we evaluated the clinical and radiologic outcomes of using both dorsal locking plates with or without augmentation with mineralized collagen (MC) bone graft for elderly patients with dorsally metaphyseal comminuted radius fractures. Patients in group 1 ( n = 12) were treated with dorsal locking plates with MC bone graft application into the metaphyseal bone defect, and those in group 2 ( n = 12) only with dorsal locking plates. Clinical and radiologic parameters were determined at three and 12 months after surgery. At final follow-up, no significant difference was noted between the 2 groups in terms of palmar tilt and radial inclination ( p = 0.80); however, ulnar variance increased significantly in the group 2 treated with dorsal locking plates without augmentation ( p < 0.05). Functionally, there was no significant difference between the groups. Our preliminary study suggests that combination of MC as bone-graft substitutes and dorsal locking plates may be a usefully alternative for elderly patients with metaphyseal comminuted distal radius fracture.

Liu, Ke-Bin; Huang, Kui; Teng, Yu; Qu, Yan-Zheng; Cui, Wei; Huang, Zhen-Fei; Sun, Ting-Fang; Guo, Xiao-Dong

2014-03-01

282

Use of mineralized collagen bone graft substitutes and dorsal locking plate in treatment of elder metaphyseal comminuted distal radius fracture  

NASA Astrophysics Data System (ADS)

Bone graft may be needed to fill bone defect in elderly patients with a metaphyseal comminuted distal radius fracture. In this retrospective, nonrandomized, single-surgeon study, we evaluated the clinical and radiologic outcomes of using both dorsal locking plates with or without augmentation with mineralized collagen (MC) bone graft for elderly patients with dorsally metaphyseal comminuted radius fractures. Patients in group 1 (n = 12) were treated with dorsal locking plates with MC bone graft application into the metaphyseal bone defect, and those in group 2 (n = 12) only with dorsal locking plates. Clinical and radiologic parameters were determined at three and 12 months after surgery. At final follow-up, no significant difference was noted between the 2 groups in terms of palmar tilt and radial inclination (p = 0.80); however, ulnar variance increased significantly in the group 2 treated with dorsal locking plates without augmentation (p < 0.05). Functionally, there was no significant difference between the groups. Our preliminary study suggests that combination of MC as bone-graft substitutes and dorsal locking plates may be a usefully alternative for elderly patients with metaphyseal comminuted distal radius fracture.

Liu, Ke-Bin; Huang, Kui; Teng, Yu; Qu, Yan-Zheng; Cui, Wei; Huang, Zhen-Fei; Sun, Ting-Fang; Guo, Xiao-Dong

2014-04-01

283

Substitute Teachers  

NSDL National Science Digital Library

Our lives are ones of uncertainty and surprise, yin and yang existences. Some things we can control and others we are powerless to command, even with the best intentions. Teachers are not exempt from emergencies, jury duty, and illness. Luckily, most schools plan for such incidents by having willing substitutes on hand. Teachers need to follow the Scout's motto to "be prepared" and keep the classroom running smoothly and efficiently for students and subs.

Swango, C. J.; Steward, Sally B.

2003-01-01

284

Buprenorphine: a reappraisal of its antinociceptive effects and therapeutic use in alleviating post-operative pain in animals  

Microsoft Academic Search

Summary Buprenorphine has been widely used for post-operative analgesia in laboratory animals. Clinical ef® cacy has been demonstrated in both subjective and objective pain assessment schemes, however doubts have been expressed as to its value as an analgesic. Initial dosage recommendations were based on analgesiometric studies. It is unlikely, however, that the pain elicited in analgesiometric tests is comparable to

J. V. Roughan; P. A. Flecknell

2002-01-01

285

Respiratory effects of buprenorphine/naloxone alone and in combination with diazepam in naive and tolerant rats.  

PubMed

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

Cohier, Camille; Chevillard, Lucie; Risède, Patricia; Roussel, Olivier; Mégarbane, Bruno

2014-07-15

286

Evaluation of butorphanol tartrate and buprenorphine hydrochloride on the inflammatory reaction of the Sereny Test.  

PubMed

Invasion of the ocular epithelia of guinea pigs by virulent Shigella organisms, eliciting keratoconjunctivitis, is the basis of the Sereny Test (ST). This test has been used to ascertain the virulence of Shigella strains and more recently to screen candidate Shigella vaccines for efficacy. This test undoubtedly causes pain in test animals; however, recommendation for use of local analgesics/anesthetics has not been accepted because of concern that these topical agents may affect the ability of the Shigella organisms to invade the ocular epithelia or have a physiologic effect on the inflammatory process. Similarly, investigators are hesitant to use systemic analgesics in conjunction with the ST. Two blinded studies were conducted to evaluate the effects of selected systemic analgesics on the ST in outbred Hartley guinea pigs. Study 1 evaluated the recommended dosages for two systemic analgesics; study groups consisted of those receiving butorphanol tartrate (n = 16), those receiving buprenorphine hydrochloride (n = 16), and untreated controls (n = 5). Study 2 evaluated a low-dose buprenorphine hydrochloride group (n = 16) and an untreated control group (n = 5). All animals were inoculated with Shigella flexneri, strain 2a 2457T, onto the cornea and conjunctiva of each eye. At the onset of clinical signs, analgesics were administered to test groups. The degree of keratoconjunctivitis was evaluated per standard procedure; animals were weighed daily. After 7 days, animals were euthanatized and the eyes were removed for histologic morphometric evaluation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8277729

Swearengen, J R; Cockman-Thomas, R A; Davis, J A; Weina, P J

1993-10-01

287

Combined effects of buprenorphine and a nondrug alternative reinforcer on IV cocaine self-administration in rats maintained under FR schedules  

Microsoft Academic Search

Although previous studies have shown that pharmacological agents, such as buprenorphine, and alternative nondrug reinforcers, such as money or sweetened solutions, reduce cocaine self-administration, few studies have examined the combined effects of these two approaches. The purpose of the present study was to evaluate the effects of the opioid partial agonist buprenorphine (0.1 mg\\/kg) and concurrent access to either water

Sandra D. Comer; Sylvie T. Lac; Cindy L. Wyvell; Marilyn E. Carroll

1996-01-01

288

Blood substitutes.  

PubMed

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. PMID:24819476

Palmer, Andre F; Intaglietta, Marcos

2014-07-11

289

Anticancer agents for treatment of tumors in the central nervous system by correspondent substituent substitution and elucidation by pattern recognition methods.  

PubMed

Within the United States, primary brain tumors account for 20 to 25 percent of all pediatric cancers. Chemotherapy utilizing a nitrosourea, notably semustine (MeCCNU) and carmustine (BCNU), has shown significant success in the treatment of tumors found in the central nervous system. In silico optimization of molecular properties by substituent substitution that is followed by pattern recognition analysis is utilized in this study to develop 14 novel anti-cancer drugs for the treatment of malignant cancers of the central nervous system. These 14 agents exhibit molecular properties that are suitable for penetration through the blood-brain barrier (BBB). All 14 agents are nitrosoureas having values of Log P ranging from 2.188 to 2.942, and having a constant total of 5 oxygens and nitrogens with zero violations of the Rule of 5 which indicates favorable bioavailability. Value of Log BB (Log [Cbrain/Cblood]) for these agents does not vary from - 0.441 (BB value of 0.362). The formula weight of the agents is highly correlated to molecular volume (r= 0.9848) and total number of atoms (r= 0.9948), but not correlated to number of rotatable bonds (r= 0.1814). Analysis of similarity (ANOSIM) indicated that all 14 new constructs are similar to the parent compound semustine. The Log P value for all 14 agents predicts favorable attributes for penetrating the BBB. Multiple regression analysis established that number of atoms, number of rotatable bonds, and molecular volume are strong prognosticators for molecular weight of this assemblage of pharmaceuticals. This study attests to the efficacy of in silico optimization of molecular substituents followed by pattern recognition analysis to develop new drug designs based on a successful nitrosourea framework for the treatment of malignant tumors of the brain. PMID:22385186

Bartzatt, Ronald

2012-03-01

290

40 CFR 721.8780 - Substituted pyridine azo substituted phenyl.  

Code of Federal Regulations, 2010 CFR

...false Substituted pyridine azo substituted phenyl. 721.8780 Section...8780 Substituted pyridine azo substituted phenyl. (a) Chemical substance...generically as substituted pyridine azo substituted phenyl (PMNs P-96-767...

2009-07-01

291

Infant neurobehavior following prenatal exposure to methadone or buprenorphine: results from the neonatal intensive care unit network neurobehavioral scale.  

PubMed

This study examined the neurobehavioral functioning of neonates prenatally exposed to methadone (n = 11) or buprenorphine (n = 10), who underwent the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) examinations on days 3, 5, 7, 10, and 14 post-delivery. Linear mixed model analyses revealed that NNNS scores of arousal and excitability showed significant differences between medications over time. Compared to neonates who did not require medication to treat neonatal abstinence syndrome (NAS), neonates receiving pharmacotherapy for NAS showed differences over time in quality of movement, excitability, and lethargy. Results suggest the NNNS may detect subtle differences over time between both neonates prenatally exposed to methadone or buprenorphine and neonates pharmacologically treated or untreated for NAS. PMID:20482340

Jones, Hendrée E; O'Grady, Kevin E; Johnson, Rolley E; Velez, Martha; Jansson, Lauren M

2010-11-01

292

US practitioner prescribing practices and patient characteristics of those newly treated with a buprenorphine transdermal patch system.  

PubMed

Abstract Objectives: Medication prescribing information provides guidance to healthcare providers on how to prescribe a drug properly. Oftentimes patient factors in addition to the prescribing information are considered when selecting medications. Utilizing real-world pharmacy and medical claims data, this study assessed US practitioner prescribing practices of US approved transdermal buprenorphine system (BTDS) in relation to BTDS's full prescribing information (FPI) as well as the relationship between patient factors and initial BTDS dose. Research design and methods: Patients aged ?18 years initiating BTDS between 1 January 2011 and 30 November 2011 were identified in the IMS Pharmacy and Private Practitioner Medical Claims databases. The index date was defined as the first filled BTDS prescription. Demographics, chronic pain-related medical conditions in the 12 months pre-index and prior medication use in the 6 months pre-index were assessed. Initial BTDS dosing strength, receipt of approved initial BTDS dose per the FPI, and concomitant medications were assessed in the post-index 6 month period. Results: The study included 10,457 patients newly treated with BTDS. The majority of patients were female (69.9%) with a mean (±SD) age of 54.5 (±15.2) years. Within the 6 months prior to the index BTDS prescription, 91.7% of the patients used opioids. Overall, 48.9% of patients were prescribed the FPI approved BTDS dose. When stratified, 73.5% of opioid-naïve patients received the FPI approved initial dose compared to 46.0% of those with prior opioid experience of ?80?mg morphine-equivalent daily dose. Patients on BTDS alone (i.e. monotherapy) had a higher rate of receiving the FPI approved initial BTDS dose compared to patients on BTDS concomitant regimens (p?treatment, setting the stage for preventing side-effects and improving treatment effectiveness. Understanding practitioner prescribing practices with regard to the initial dose selection of BTDS may provide insight on how to improve outcomes of care and reduce healthcare resource utilization and costs associated with pain management. Limitations: Data obtained from prescription claims reflect only the activities of prescriptions filled, not medication use or other clinical characteristics observed by physicians when treating patients. PMID:24689806

Pergolizzi, Joseph V; Ben-Joseph, Rami; Chang, Chun-Lan; Hess, Gregory

2014-08-01

293

A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network  

PubMed Central

Aims The clinical effectiveness of buprenorphine–naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network. Design Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2:1 ratio favoring bup-nx, to a 13-day detoxification using bup-nx or clonidine. Methods A total of 113 in-patients (77 bup-nx, 36 clonidine) and 231 out-patients (157 bup-nx, 74 clonidine) participated. Supportive interventions included appropriate ancillary medications and standard counseling procedures guided by a self-help handbook. The criterion for treatment success was defined as the proportion of participants in each condition who were both retained in the study for the entire duration and provided an opioid-free urine sample on the last day of clinic attendance. Secondary outcome measures included use of ancillary medications, number of side effects reported and withdrawal and craving ratings. Findings A total of 59 of the 77 (77%) in-patients assigned to the bup-nx condition achieved the treatment success criterion compared to eight of the 36 (22%) assigned to clonidine, whereas 46 of the 157 (29%) out-patients assigned to the bup-nx condition achieved the treatment success criterion, compared to four of the 74 (5%) assigned to clonidine. Conclusion The benefits of bup-nx for opioid detoxification are supported and illustrate important ways in which clinical research can be conducted in community treatment programs.

Ling, Walter; Amass, Leslie; Shoptaw, Steve; Annon, Jeffrey J.; Hillhouse, Maureen; Babcock, Dean; Brigham, Greg; Harrer, Judy; Reid, Malcolm; Muir, Joan; Buchan, Betty; Orr, Debbie; Woody, George; Krejci, Jonathan; Ziedonis, Douglas; Group, the Buprenorphine Study Protocol

2005-01-01

294

Differential Involvement of P-Glycoprotein (ABCB1) in Permeability, Tissue Distribution, and Antinociceptive Activity of Methadone, Buprenorphine, and Diprenorphine: In Vitro and In Vivo Evaluation  

PubMed Central

Conclusions based on either in vitro or in vivo approach to evaluate the P-gp affinity status of opioids may be misleading. For example, in vitro studies indicated that fentanyl is a P-gp inhibitor while in vivo studies indicated that it is a P-gp substrate. Quite the opposite was evident for meperidine. The objective of this study was to evaluate the P-gp affinity status of methadone, buprenorphine and diprenorphine to predict P-gp-mediated drug-drug interactions and to determine a better candidate for management of opioid dependence. Two in vitro (P-gp ATPase and monolayer efflux) assays and two in vivo (tissue distribution and antinociceptive evaluation in mdr1a/b (?/?) mice) assays were used. Methadone stimulated the P-gp ATPase activity only at higher concentrations, while verapamil and GF120918 inhibited its efflux (p <0.05). The brain distribution and antinociceptive activity of methadone were enhanced (p <0.05) in P-gp knockout mice. Conversely, buprenorphine and diprenorphine were negative in all assays. P-gp can affect the PK/PD of methadone, but not buprenorphine or diprenorphine. Our report is in favor of buprenorphine over methadone for management of opioid dependence. Buprenorphine most likely is not a P-gp substrate and concerns regarding P-gp-mediated drug-drug interaction are not expected.

HASSAN, HAZEM E.; MYERS, ALAN L.; COOP, ANDREW; EDDINGTON, NATALIE D.

2012-01-01

295

Faculty Development in Small-Group Teaching Skills Associated with a Training Course on Office-Based Treatment of Opioid Dependence  

ERIC Educational Resources Information Center

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…

Wong, Jeffrey G.; Holmboe, Eric S.; Becker, William C.; Fiellin, David A.; Jara, Gail B.; Martin, Judith

2005-01-01

296

Trends in the Use of Methadone and Buprenorphine at Substance Abuse Treatment Facilities: 2003 to 2011.  

National Technical Information Service (NTIS)

An estimated 2 million people in the United States are dependent upon or abuse opioids, including heroin and prescription opioids such as oxycodone and hydrocodone. Withdrawal from these drugs is generally so intense that those who are dependent upon them...

2013-01-01

297

Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model: a double-blind, randomized, placebo-controlled, five-arm crossover study  

PubMed Central

Purpose Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than ?-opioid receptor agonists. The primary outcome of this study was therefore to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending pain modulation. Subjects and methods Twenty-eight healthy subjects were included. The study was a double-blind, randomized, placebo-controlled, five-arm crossover study with a multimodal (electrical, mechanical, and thermal stimuli) testing technique. After baseline assessments, intravenous infusions of morphine (10/20 mg), buprenorphine (0.3/0.6 mg), or placebo (normal saline) were administered over a 210-minute period, during which a cold pressor test, heat injury (47°C, 7 minutes, 12.5 cm2), and the first postburn assessment were done. After completion of the drug infusions, two additional postburn assessments were done. The subjects were monitored during each 8-hour session by an anesthesiologist. Results For nearly all tested variables, significant dose-dependent analgesic effects were demonstrated. The median antihyperalgesia/analgesia ratio (secondary hyperalgesia/heat injury relative to placebo) for low-dose morphine was 0.01 (interquartile range: ?6.2; 9.9), 0.00 (?2.4; 2.1) for high-dose morphine, 0.03 (?1.8; 2.1) for low-dose buprenorphine, and 0.00 (?3.2; 1.1) for high-dose buprenorphine (P > 0.466). There were no significant differences in opioid responses between high and low pain-sensitive subjects (P > 0.286). High-dose buprenorphine, compared to placebo, was associated with a significantly enhanced action of the descending inhibitory pain control system (P = 0.004). Conclusion The present study, using multimodal testing technique, could not demonstrate any significant differences between morphine and buprenorphine in the profiles of antihyperalgesia and analgesia. Only high-dose buprenorphine was associated with a significant effect on the descending inhibitory pain control system.

Ravn, Pernille; Secher, Erik L; Skram, Ulrik; Therkildsen, Trine; Christrup, Lona L; Werner, Mads U

2013-01-01

298

Nucleophilic Aromatic Substitution.  

ERIC Educational Resources Information Center

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)

Avila, Walter B.; And Others

1990-01-01

299

Compositions and Methods Containing Substituted Quinolines and Substituted Diphenylsufones.  

National Technical Information Service (NTIS)

Combination therapies of substituted quinolines and substituted diphenyl sulfones are disclosed. More specifically, compositions containing substituted quinolines and substituted diphenyl sulfones are disclosed. In addition, methods of using the compositi...

D. J. Giulian D. P. Jacobus

2004-01-01

300

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

Code of Federal Regulations, 2010 CFR

...substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl...

2009-07-01

301

Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients  

Microsoft Academic Search

Up to 1999 more opioid dependent patients in Germany were substituted with codeine or dihydrocodeine (summarised as codeine) than with methadone. The current retrospective study compares the differences in detoxification treatment outcome for codeine-substituted patients, methadone-substituted patients and patients injecting illicit heroin. The study is based on the medical records of 1070 patients admitted consecutively for opioid and polytox detoxification

Markus Backmund; Kirsten Meyer; Dieter Eichenlaub; Christian G. Schütz

2001-01-01

302

Medication-assisted treatment of opiate dependence is gaining favor.  

PubMed

People addicted to opiates are more likely to avoid returning to these drugs if they participate in a program that includes taking maintenance doses of methadone or buprenorphine than with an abstinence program. Although medical opinion has long been divided on the issue of abstinence vs medication-assisted treatment, the latter seems to be gaining respect as an evidence-based approach. PMID:23733899

Jerry, Jason M; Collins, Gregory B

2013-06-01

303

[Management of opioid maintenance treatments when analgesic treatments are required].  

PubMed

Opioid maintenance treatments (OMT) reduce illicit opiate use and its associated risks. They are often prescribed on a long-term basis. Physiological changes induced by long-term OMT may cause hyperalgesia and cross-tolerance to opioid agonists, which suggests that the dosage of analgesic treatment should be modified in cases of acute pain, especially when an opioid-based analgesia is required. When treatment with analgesics is necessary, OMT must be maintained, except in exceptional cases. If a split-dosing schedule is temporarily employed during OMT, the daily dosage should not be increased for analgesic purposes. Analgesic treatment must be managed differently in case of treatment with buprenorphine or methadone. With buprenorphine, non-opioid analgesics should be introduced first, if possible. If this strategy is inefficient or contraindicated, a temporary or definitive switch to methadone should be considered. In the case of methadone-based OMT, opioid analgesics should be added directly and the dosage should be adapted according to the level of pain reported by the patient. PMID:23518339

Laprevote, Vincent; Geoffroy, Pierre A; Rolland, Benjamin; Leheup, Benoît F; Di Patrizio, Paolo; Cottencin, Olivier; Schwan, Raymund

2013-01-01

304

Yohimbine Increases Opioid-Seeking Behavior in Heroin-Dependent, Buprenorphine-Maintained Individuals  

PubMed Central

Rationale In laboratory animals, the biological stressor yohimbine (?2-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.

Greenwald, Mark K.; Lundahl, Leslie H.; Steinmiller, Caren L.

2012-01-01

305

Differential-Pulse Polarographic Determination of Some N-Substituted Phenothiazine Derivatives in Dosage Forms and Urine Through Treatment with Nitrous Acid  

Microsoft Academic Search

.  ?A highly sensitive differential-pulse (DPP) polarographic method is described for the determination of three N-substituted\\u000a phenothiazine derivatives, chlorpromazine (CZ), promazine (PZ) and promethazine (PMZ). The method involves the use of nitrous\\u000a acid as an oxidant. Polarographically-active sulphoxides with diffusion-current constants (Id) of 2.53, 3.05 and 3.37 were\\u000a obtained for CZ, PZ and PMZ, respectively. The polarographic waves were characterized as

Fathalla Belal; Saadia M. El-Ashry; Ihsan M. Shehata; Magda A. El-Sherbeny; Dina T. El-Sherbeny

2000-01-01

306

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

PubMed Central

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.

2014-01-01

307

Incorporation of drugs for the treatment of substance abuse into pigmented and nonpigmented hair  

Microsoft Academic Search

Hair analysis for drugs may be useful for the long-term monitoring of recidivism and treatment compliance. L-R-Acetylmeth- adol, buprenorphine, and methadone are drugs that are used for the treatment of substance abuse. The purpose of this study was to study the relationship between dose, plasma concentration, hair concentration, and hair pigmentation for these compounds and their major metabolites in an

Diana G. Wilkins; Angelique S. Valdez; Pamela R. Nagasawa; Steven P. Gygi; Douglas E. Rollins

1998-01-01

308

A comparative study of the use of bioactive glass S53P4 and antibiotic-loaded calcium-based bone substitutes in the treatment of chronic osteomyelitis: a retrospective comparative study.  

PubMed

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed. In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups. After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate. Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes. Cite this article: Bone Joint J 2014; 96-B:845-50. PMID:24891588

Romanò, C L; Logoluso, N; Meani, E; Romanò, D; De Vecchi, E; Vassena, C; Drago, L

2014-06-01

309

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

PubMed

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 5.0nM and 72.0nM and a limit of detection (LOD, 3Sb/b) of 1.5nM 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 performance liquid chromatography-ultraviolet detection (HPLC-UV). It is expected that the distinctive features of BSA/MWCNTs nanobiocomposite would make it potentially advantageous for a broad range of biosensing, and clinical applications. PMID:24767442

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

2014-06-15

310

Bone substitutes: new concepts  

Microsoft Academic Search

The filling of bone defects resulting from trauma or surgical resections of tumors requires bone grafts or bone substitutes. Bone substitute must be biocompatible, osteoconductive, and must present good mechanical properties. Among biomaterials classicaly used, calcium phosphate ceramic appear to be suitable alternatives to bone grafts. Calcium phosphate are known able to promote new bone formation on contact and have

D. Heymann; N. Passuti

1999-01-01

311

[Estrogen substitution and endometrial carcinoma].  

PubMed

Perimenopausal and postmenopausal substitutive estrogen treatment is valuable if prescribed according to proper indications and in the proper manner. Studies have shown a correlation between menopausal estrogen treatment and endometrial cancer. Siiteri hypothesized that estrone was the estrogen with a specific carcinogenic effect. A study undertaken in California indicates, however, that conjugated estrogens are associated with a lower risk of endometrial cancer. There is also strong indications that certain factors predispose a woman to endometrial cancer during menopausal estrogen treatment: obesity, the Stein-Leventhal syndrone, the Turner syndrome, hirsuitism caused by increased androgen activity, and family history of endometrial cancer. Menopausal estrogen treatment is prescribed in cases of menstrual disturbances, neurovegetative or vaso-motor disturbances, psychological disturbances, atrophy of the urogenital tract, or cases of calcium or fat metabolism disturbances which could lead to osteoporosis or arteriosclerosis. PMID:216933

Kruyver, G P

1979-03-10

312

Bioactive glass granules: a suitable bone substitute material in the operative treatment of depressed lateral tibial plateau fractures: a prospective, randomized 1 year follow-up study.  

PubMed

Purpose of this study was to compare bioactive glass and autogenous bone as a bone substitute material in tibial plateau fractures. We designed a prospective, randomized study consisting of 25 consecutive operatively treated patients with depressed unilateral tibial comminuted plateau fracture (AO classification 41 B2 and B3).14 patients (7 females, 7 males, mean age 57 years, range 25-82) were randomized in the bioglass group (BG) and 11 patients (6 females, 5 males, mean age 50 years, range 31-82) served as autogenous bone control group (AB). Clinical examination of the patients was performed at 3 and 12 months, patients' subjective and functional results were evaluated at 12 months. Radiological analysis was performed preoperatively, immediately postoperatively and at 3 and 12 months. The postoperative redepression for both studied groups was 1 mm until 3 months and remained unchanged at 12 months. No differences were identified in the subjective evaluation, functional tests and clinical examination between the two groups during 1 year follow-up. We conclude that bioactive glass granules can be clinically used as filler material instead of autogenous bone in the lateral tibial plateau compression fractures. PMID:21431354

Heikkilä, Jouni T; Kukkonen, Juha; Aho, Allan J; Moisander, Susanna; Kyyrönen, Timo; Mattila, Kimmo

2011-04-01

313

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

PubMed

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

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

2013-04-15

314

Skin Substitutes and Uses Thereof.  

National Technical Information Service (NTIS)

The present invention relates to in vitro cultured skin substitutes, and in particular to improved methods for organotypic culture of skin substitutes. In some embodiments, the dermal equivalent of the skin substitute is lifted to air interface of the cul...

C. A. R. Ivarie L. A. Hoffman P. Barth

2004-01-01

315

Client and Counselor Attitudes Toward the Use of Medications for Treatment of Opioid Dependence  

PubMed Central

Attitudes, perceived social norms and intentions were assessed for 376 counselors and 1083 clients from outpatient, methadone and residential drug treatment programs regarding four medications used to treat opiate dependence: methadone, buprenorphine, clonidine, and ibogaine. Attitudes, social norms and intentions to use varied by treatment modality. Methadone clients and counselors had more positive attitudes toward the use of methadone, while their counterparts in residential and outpatient settings had neutral or negative assessments. Across modalities, attitudes, perceived social norms, and intentions toward the use of buprenorphine were relatively neutral. Assessments of clonidine and ibogaine were negative for clients and counselors in all settings. Social normative influences were dominant across settings and medications in determining counselor and client intentions to use medications, suggesting that perceptions about beliefs of peers may play a critical role in use of medications to treat opiate dependence.

Rieckmann, Traci; Daley, Marilyn; Fuller, Bret E.; Thomas, Cindy P.; McCarty, Dennis

2009-01-01

316

Analgesia after feline ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia with buprenorphine or butorphanol, and carprofen or meloxicam: a prospective, randomised clinical trial  

Microsoft Academic Search

One hundred female cats undergoing routine ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia were included in a blinded, randomised, prospective clinical study to compare postoperative analgesia produced by four analgesic drug combinations given preoperatively (n = 25 per group). A secondary aim was to assess the effects in kittens and pregnant animals. Buprenorphine 180 µg\\/m2 or butorphanol 6 mg\\/m2 were given with either

Sally Polson; Polly M Taylor; David Yates

2012-01-01

317

Sugar Substitutes: Aspartame  

MedlinePLUS

... sugar substitute. It is a combination of 2 amino acids, aspartic acid and phenylalanine. It is about 220 ... bodies are unable to metabolize one of the amino acids in aspartame, phenylalanine. Benefits of aspartame Does not ...

318

Execution of control among 'non-compliant', imprisoned individuals in opioid maintenance treatment.  

PubMed

Strict control routines of prescribed opiate intake in opioid maintenance treatment, OMT, are used to reduce the risk of diversion and non-prescribed methadone and buprenorphine use. While maintaining a focus on aspects of control, this article explores motivations for and practices of methadone and buprenorphine use, both inside and outside of prison and among imprisoned individuals in OMT. The participants in this qualitative study were subjected to tight external control regimes in their opioid maintenance schemes in prison, as they were prior to imprisonment due to varying degrees of 'non-compliance'. We nevertheless found them to exhibit a considerable amount of self-control, self-regulation and/or self-initiation of external control. Among the participants, a ceaseless surveillance of processes associated with methadone and buprenorphine use throughout diverse situations, relations and contexts was encountered. We conclude that, in opioid maintenance treatment, some individuals might know what particular configurations of internal and external control they need in order to achieve their own treatment goals. The drug users' capacities for execution of control, as well as their delegations of control to others, may be seen as resources throughout the course of treatment. PMID:24594221

Havnes, Ingrid Amalia; Clausen, Thomas; Middelthon, Anne-Lise

2014-05-01

319

Substitution of anticonvulsant drugs  

PubMed Central

Changing from branded drugs to generic alternatives, or between different generic formulations, is common practice aiming at reducing health care costs. It has been suggested that antiepileptic drugs (AEDs) should be exempt from substitution because of the potential negative consequences of adverse events and breakthrough seizures. Controlled data are lacking on the risk of substitution. However, retrospective data from large medical claims databases suggest that switching might be associated with increased use of AED and non-AED medications, and health care resources (including hospitalization). In addition, some anecdotal evidence from patients and health care providers’ surveys suggest a potentially negative impact of substitution. Well-controlled data are needed to assess the real risk associated with substitution, allowing health care professionals involved in the care of patients with epilepsy to make informed decisions. This paper reviews currently available literature, based on which the authors suggest that the decision to substitute should be made on an individual basis by the physician and an informed patient. Unendorsed or undisclosed substitution at the pharmacy level should be discouraged.

Steinhoff, Bernhard J; Runge, Uwe; Witte, Otto W; Stefan, Hermann; Hufnagel, Andreas; Mayer, Thomas; Kramer, Gunter

2009-01-01

320

Catch-Up Growth after Childhood-Onset Substitution in Primary Hypothyroidism: Is It a Guide towards Optimal Growth Hormone Treatment in Idiopathic Growth Hormone Deficiency?  

Microsoft Academic Search

Catch-up growth was analyzed in 20 prepubertal children with primary hypothyroidism (PH) starting treatment at an age of 4.4 (1.2–10.1) years and a height (HT) SD score (HT SDS) of –3.1 (±0.8). All patients were followed for at least 3 prepubertal years. HT velocity was 12.3 ± 2.3, 9.0 ± 1.8 and 7.5 ± 2.2 cm\\/year, and change in HT

M. B. Ranke; C. P. Schwarze; K. Mohnike; K. E. von Mühlendahl; E. Keller; H. Willgerodt; W. Kiess

1998-01-01

321

Substitute Valuations: Generation and Structure  

Microsoft Academic Search

Substitute valuations (in some contexts called gross substitute valuations) are promi- nent in combinatorial auction theory. An algorithm is given in this paper for gen- erating a substitute valuation through Monte Carlo simulation. In addition, the geometry of the set of all substitute valuations for a fixed number of goods K is investigated. The set consists of a union of

Bruce Hajek

2007-01-01

322

An attempted substitute study of total skin electron therapy technique by using helical photon tomotherapy with helical irradiation of the total skin treatment: a phantom result.  

PubMed

An anthropomorphic phantom was used to investigate a treatment technique and analyze the dose distributions for helical irradiation of the total skin (HITS) by helical tomotherapy (HT). Hypothetical bolus of thicknesses of 0, 10, and 15 mm was added around the phantom body to account for the dose homogeneity and setup uncertainty. A central core structure was assigned as a "complete block" to force the dose tangential delivery. HITS technique with prescribed dose (D p ) of 36 Gy in 36 fractions was generated. The radiochromic EBT2 films were used for the dose measurements. The target region with 95.0% of the D p received by more than 95% of the PTV was obtained. The calculated mean doses for the organs at risk (OARs) were 4.69, 3.10, 3.20, and 2.94 Gy for the lung, heart, liver, and kidneys, respectively. The measurement doses on a phantom surface for a plan with 10 mm hypothetical bolus and bolus thicknesses of 0, 1, 2, and 3 mm are 89.5%, 111.4%, 116.9%, and 117.7% of D p , respectively. HITS can provide an accurate and uniform treatment dose in the skin with limited doses to OARs and is safe to replace a total skin electron beam regimen. PMID:23984313

Lin, Chi-Ta; Shiau, An-Cheng; Tien, Hui-Ju; Yeh, Hsin-Pei; Shueng, Pei-Wei; Hsieh, Chen-Hsi

2013-01-01

323

The substitutability of reinforcers  

PubMed Central

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.

Green, Leonard; Freed, Debra E.

1993-01-01

324

40 CFR 721.10040 - Substituted acridine naphtha substituted benzamide (generic).  

Code of Federal Regulations, 2010 CFR

... 2009-07-01 false Substituted acridine naphtha substituted benzamide (generic...Substances § 721.10040 Substituted acridine naphtha substituted benzamide (generic...identified generically as a substituted acridine naphtha substituted benzamide...

2009-07-01

325

40 CFR 721.10040 - Substituted acridine naphtha substituted benzamide (generic).  

Code of Federal Regulations, 2010 CFR

... 2010-07-01 false Substituted acridine naphtha substituted benzamide (generic...Substances § 721.10040 Substituted acridine naphtha substituted benzamide (generic...identified generically as a substituted acridine naphtha substituted benzamide...

2010-07-01

326

40 CFR 721.10040 - Substituted acridine naphtha substituted benzamide (generic).  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 false Substituted acridine naphtha substituted benzamide (generic...Substances § 721.10040 Substituted acridine naphtha substituted benzamide (generic...identified generically as a substituted acridine naphtha substituted benzamide...

2013-07-01

327

The Age of Substitutability  

ERIC Educational Resources Information Center

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…

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

1976-01-01

328

Performing Substitute Teaching  

ERIC Educational Resources Information Center

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.…

Bletzer, Keith V.

2010-01-01

329

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

Code of Federal Regulations, 2010 CFR

...substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo substituted benzenesulfonic acid copper compound (generic). 721.10126 Section 721.10126 Protection...

2010-07-01

330

Determination of buprenorphine by differential pulse voltammetry on carbon paste electrode using SDS as an enhancement factor.  

PubMed

In the present study, a facile electrochemical approach is proposed for the determination of buprenorphine (BPR) in the presence of sodium dodecyl sulfate (SDS). SDS was applied for amplification of oxidation signal. Carbon paste electrode (CPE) used as working electrode and cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) were carried out in phosphate buffer solution (pH3.0). Under optimal experimental conditions, the oxidation current increased with the addition of BPR in the sample and two dynamic ranges obtained from 4.00nM to 0.126?M and from 0.126 to 0.317?M by DPV and exhibited a low detection limit (LOD) of 1.33nM (S/N=3). This offered method has been used for the determination of BPR in the real samples and has validated with the recovery test for BPR spiked urine samples. The result demonstrated that this method is a simple, sensitive, rapid, low-cost, and stable method for BPR detection. PMID:25063147

Behpour, Mohsen; Valipour, Akram; Keshavarz, Mahin

2014-09-01

331

Explicit Substitutions and All That.  

National Technical Information Service (NTIS)

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 pro...

M. Ayala-Rincon C. Munoz

2000-01-01

332

[Primary health care and family medicine--possibilities for treatment of opiate addicts].  

PubMed

The global trend of promoting management and treatment of drug addicts in family physician offices is the result of the success of opioid agonist therapy. Studies have shown favorable results by shifting treatment into the hands of family physician. This process contributes to general health care of drug addicts and their health by linking different areas of health care, thereby providing comprehensive protection. Shifting treatment of addiction to family physician offices contributes to the elimination of treatment isolation and stigmatization, while further benefits are lower barriers to employment, increase in patient privacy and opportunity to provide health care. The aim of this study was to provide a concise overview of the knowledge from new clinical research over the past ten years on heroin addiction treatment in primary care. New research dealing with the approach to treating addicts indicates a direct link between receiving primary health care with a reduced likelihood of using heroin; furthermore, the main concerns of drug addicts for treatment are availability of more therapeutic programs, better functioning of existing programs, and improved staff relations towards them; final results and outcomes achieved by office and hospital treatment of drug addicts are similar and confirm the positive linear relationship between treatment duration and outcome. Studies comparing therapies show a positive effect of the adaptive methadone treatment maintenance model on the psychosocial factors; equal efficiency of treatment regardless of initiation with buprenorphine or with methadone; and equal effectiveness of levo-alpha-acetylmethadol treatment compared with methadone and diacetylmorphine as a good alternative for addiction therapy with previously unsatisfactory results. New studies on buprenorphine show equal effectiveness and cost of detoxification whether guided by a family physician or at the hospital; non-supervised therapy does not significantly influence the outcome, but is significantly cheaper; long-term therapy with buprenorphine in the doctor's office shows mild retention. PMID:23814972

Tiljak, Hrvoje; Nerali?, Ivana; Cerovecki, Venija; Kastelic, Andrej; Adzi?, Zlata Ozvaci?; Tiljak, Anja

2012-10-01

333

Factor substitution in nursing homes  

Microsoft Academic Search

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

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

2006-01-01

334

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

PubMed

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 ?-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

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

335

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...

336

U.S. Food and Drug Administration Approval Summary: Erlotinib for the First-Line Treatment of Metastatic Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 (L858R) Substitution Mutations.  

PubMed

On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib (Tarceva, Astellas Pharma Inc., Northbrook, IL, http://www.us.astellas.com/) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. This indication for erlotinib was approved concurrently with the cobas EGFR Mutation Test (Roche Molecular Systems, Inc., Basel, Switzerland, http://www.molecular.roche.com), a companion diagnostic test for patient selection. The approval was based on clinically important improvements in progression-free survival (PFS) and objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open label trial enrolling 174 patients with metastatic NSCLC whose tumors had EGFR mutations as determined by a laboratory-developed test. Patients were randomized (1:1) to receive erlotinib (150 mg/day) or platinum-based doublet chemotherapy. The primary endpoint was investigator-assessed PFS. Secondary endpoints included overall survival (OS) and ORR. Superior PFS (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.23, 0.49; p < .001) and ORR (65% vs. 16%) were observed in the erlotinib arm. Median PFS was 10.4 months and 5.2 months in the erlotinib and chemotherapy arms, respectively. There was no difference in OS (HR 0.93; 95% CI: 0.64, 1.35) with median OS of 22.9 months and 19.5 months in the erlotinib and chemotherapy arms, respectively. The most frequent (?30%) adverse reactions in the erlotinib-treated patients were rash, diarrhea, asthenia, cough, dyspnea, and decreased appetite. The most frequent (?5%) grade 3 and 4 adverse reactions were rash and diarrhea. PMID:24868098

Khozin, Sean; Blumenthal, Gideon M; Jiang, Xiaoping; He, Kun; Boyd, Karen; Murgo, Anthony; Justice, Robert; Keegan, Patricia; Pazdur, Richard

2014-07-01

337

Trifluoromethyl-substituted polymers  

NASA Technical Reports Server (NTRS)

Current work sponsored by the grant at Southwest Texas State University is directed toward the synthesis and characterization of: (1) N-alkylated polyamides derived from o-fluorinated diacids; (2) highly fluorinated polyethers; (3) polyesters derived from 2-hydroxy-2-propyl substituted arenes and/or 2,5-difluoroterephthalic acid; and (4) silicon-containing fluoropolymers. Work during the period from 1 July to 31 Dec. 1993 focused primarily on items 3 and 4 and on the development of a phosphorus containing modification of '12F-PEK.'

1993-01-01

338

[Use of a Transtec transdermal therapeutic system of buprenorphine for analgesia in the early periods after cardiosurgical operations].  

PubMed

The analgesic effect of a transdermal therapeutic system (TTS) (Transtec) of buprenorphine was evaluated for analgesia in cardiosurgical patients in the early postoperative period. Before sternotomy, Transtec was applied to the skin of the shoulder in 30 patients operated on the heart under extracorporeal circulation. A control group comprised 20 patients receiving the nonsteroidal anti-inflammatory agent Xifocam in an intravenous dose of 8 mg twice daily. The first injection of Xefocam was made 1.5-2 hours prior to tracheal extubation. With the use of Transtec, the degree of pain was 1.58 scores by the five-score scale at the moment of tracheal extubation; it reduced to 1 score 16 hours after extrubation; it was 0.76 scores by the end of the first day, less than 0.5 score by the middle of day 2, reduced to zero by the end of day 3. By the moment of tracheal extubation, the degree of pain in patients receiving Xefocam was 3 scores; by the end of 24 hours, it reduced to 2 scores and remained the same by the end of day 3. During more effective analgesia with Transtec, inspiratory lung capacity was much higher than during that with Xefocam. The difference in the mean values of this parameter was 510 to 830 ml (p < 0.05) at the stages of the investigation. The findings confirmed a rather long (72-hour) continuous and steady analgesic effect of Transtec TTS. Due to the analgesic effect of Transtec, there was a significant improvement of respiratory function in patients after cardiothoracic operations. PMID:17184061

Eremenko, A A; Urbanov, A V; Avetisian, M I

2006-01-01

339

[Bone substitutes: Classification and concerns].  

PubMed

Autograft is considered as the "gold standard" for bone reconstruction. It provides osteoinductive factors, osteogenic cells, and appropriate osteoconductive scaffold. Donor site morbidity is the main limitation of autograft. Donor disease transmission limits the use of allograft. Synthetic bone substitutes still lack osteoinductive or osteogenic properties. Composite bone substitutes combining synthetic scaffold and biochemical substances initiating proliferation and cell differentiation, and possibly osteogenesis. Bone substitutes and grafts intended for clinical use are listed. PMID:21783214

Chai, F; Raoul, G; Wiss, A; Ferri, J; Hildebrand, H F

2011-09-01

340

Explicit Substitutions and All That  

NASA Technical Reports Server (NTRS)

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.

Ayala-Rincon, Mauricio; Munoz, Cesar

2000-01-01

341

Determinants of the availability of hepatitis C testing services in opioid treatment programs: results from a national study.  

PubMed

Objectives. We examined trends and organizational-level correlates of the availability of HCV testing in opioid treatment programs. Methods. We used generalized ordered logit models to examine associations between organizational characteristics of 383 opioid treatment programs from the 2005 and 2011 National Drug Abuse Treatment System Survey and HCV testing availability. Results. Between 2005 and 2011, the proportion of opioid treatment programs offering HCV testing increased but largely because of increases in off-site referrals rather than on-site testing. HCV testing availability was higher in opioid treatment programs affiliated with a hospital and those receiving federal funds. Opioid treatment programs providing both methadone and buprenorphine were more likely to offer any HCV testing, whereas opioid treatment programs providing only buprenorphine treatment were less likely to offer on-site testing. HCV testing availability was associated with more favorable staff-to-client ratios. Conclusions. The increasing use of off-site referrals for HCV testing in opioid treatment programs likely limits opportunities for case finding, prevention, and treatment. Declines in federal funding for opioid treatment programs may be a key determinant of the availability of HCV testing in opioid treatment programs. PMID:24825236

Frimpong, Jemima A; D'Aunno, Thomas; Jiang, Lan

2014-06-01

342

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

Code of Federal Regulations, 2013 CFR

... false Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega...10214 Poly(oxyalkylenediyl),.alpha.-substituted carbomonocycle-.omega...generically as poly(oxyalkylenediyl),.alpha.-substituted...

2013-07-01

343

Iridium-Catalyzed Allylic Substitution  

Microsoft Academic Search

Iridium-catalyzed asymmetric allylic substitution has become a valuable method to prepare products from the addition of nucleophiles at the more substituted carbon of an allyl unit. The most active and selective catalysts contain a phosphoramidite ligand possessing at least one arylethyl substituent on the nitrogen atom of the ligand. In these systems, the active catalyst is generated by a base-induced

John F. Hartwig; Mark J. Pouy

2011-01-01

344

Dynamical properties of logical substitutions  

Microsoft Academic Search

This is an expository paper on the dynamical properties of substitutions in\\u000apropositional many-valued logics. We identify substitutions with endomorphisms\\u000aof free algebras, and we study their actions on the dual spectral spaces.

Giovanni Panti

2006-01-01

345

Biotransformation and Biodegradation of N-Substituted Aromatics in Methanogenic Granular Sludge  

Microsoft Academic Search

N-substituted aromatic compounds are environmental contaminants associated with the production and use of dyes, explosives, pesticides and pharmaceuticals among others. Nitro- and azo-substituted aromatic compounds with strong electron withdrawing groups are poorly biodegradable in aerobic treatment systems. Therefore anaerobic treatment technologies were considered in this research. The toxicity of these compounds to methanogenic bacteria was studied. Batch toxicity assays indicated

E. Razo Flores

1997-01-01

346

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

ERIC Educational Resources Information Center

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…

Gershenson, Seth

2012-01-01

347

40 CFR 721.9545 - Substituted phenyl azo substituted sulfocarbopolycle, sodium salt.  

Code of Federal Regulations, 2010 CFR

... 2009-07-01 2009-07-01 false Substituted phenyl azo substituted sulfocarbopolycle, sodium salt. 721.9545...Specific Chemical Substances § 721.9545 Substituted phenyl azo substituted sulfocarbopolycle, sodium...

2009-07-01

348

40 CFR 721.5867 - Substituted phenol.  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 false Substituted phenol. 721.5867 Section 721.5867 ...Substances § 721.5867 Substituted phenol. (a) Chemical substance and significant...substance generically identified as substituted phenol (PMNs P-89-1125,...

2013-07-01

349

40 CFR 721.9488 - Substituted resorcinols.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Substituted resorcinols. 721.9488 Section 721.9488...Substances § 721.9488 Substituted resorcinols. (a) Chemical substance and significant...identified generically as substituted resorcinols (PMNs P-95-1103,...

2010-07-01

350

40 CFR 721.9488 - Substituted resorcinols.  

Code of Federal Regulations, 2010 CFR

...2009-07-01 false Substituted resorcinols. 721.9488 Section 721.9488...Substances § 721.9488 Substituted resorcinols. (a) Chemical substance and significant...identified generically as substituted resorcinols (PMNs P-95-1103,...

2009-07-01

351

Development and application of carbon nanotubes assisted electromembrane extraction (CNTs/EME) for the determination of buprenorphine as a model of basic drugs from urine samples.  

PubMed

In this work carbon nanotubes assisted electromembrane extraction (CNTs/EME) coupled with capillary electrophoresis (CE) and ultraviolet (UV) detection was developed for the determination of buprenorphine as a model of basic drugs from urine samples. Carbon nanotubes reinforced hollow fiber was used in this research. Here the CNTs serve as a sorbent and provide an additional pathway for solute transport. The presence of CNTs in the hollow fiber wall increased the effective surface area and the overall partition coefficient on the membrane; and lead to an enhancement in the analyte transport. For investigating the influence of the presence of CNTs in the SLM on the extraction efficiency, a comparative study was carried out between EME and CNTs/EME methods. Optimization of the variables affecting these methods was carried out in order to achieve the best extraction efficiency. Optimal extractions were accomplished with NPOE as the SLM, with 200V as the driving force, and with pH 2.0 in the donor and pH 1.0 in the acceptor solutions with the whole assembly agitated at 750rpm after 25min and 15min for EME and CNTs/EME, respectively. Under the optimized conditions, in comparison with the conventional EME method, CNTs/EME provided higher extraction efficiencies in shorter time. This method provided lower limit of detection (1ngmL(-1)), higher preconcentration factor (185) and higher recovery (92). Finally, the applicability of this method was evaluated by the extraction and determination of buprenorphine in patients' urine samples. PMID:23452789

Hasheminasab, Kobra Sadat; Fakhari, Ali Reza

2013-03-12

352

[Ileal bladder substitute].  

PubMed

The history of urinary diversion in general began in 1852 and started right away with continent diversion, i.e., ureterosigmoidostomy. Anastomosing an intestinal reservoir to the urethra was proposed by Tizzoni and Foggi in 1888. They replaced the bladder by an isoperistaltic ileal segment which was interposed between ureters and urethra in a female dog. In 1951 Couvelaire reactivated this idea of an ileal bladder substitute. Retrospectively many disappointing results of urinary diversion were often not caused by insufficient competence of the outlet mechanism, but because the intestinal reservoir maintained its peristaltic properties causing high pressure peaks. The decisive advance in ensuring continence, and thus an improvement in patient comfort, was achieved with the so-called low pressure reservoir. The main characteristics of this reservoir compared to those from intact intestinal segments are the larger diameter, the greater capacity with significantly low pressures, and the uncoordinated contraction of its wall. Transsection of the circular intestinal musculature when performing bladder augmentation had already been published by Rutkowski in 1899, Tasker in 1953, and Giertz in 1957. In 1969, Kock published the first results obtained with an ileal continent fecal reservoir in patients after total proctocolectomy. The significant advantages of interrupting the tubular structure of a reservoir obtained from intestine had been described much earlier. The need for reflux prevention is not the same as in ureterosigmoidostomy conduit or continent diversion. Reflux prevention in neobladders is even less important than in a normal bladder. When using nonrefluxing techniques, the risk of obstruction is at least twice that after direct anastomosis. Kidney function is not impaired by diversion if stenosis is recognized and managed. Patient health status is influenced more by underlying disease than by diversion. Orthotopic reconstruction has passed the test of time. In these patients life is similar to that in individuals with a native lower urinary tract. Until a better solution is devised orthotopic bladder reconstruction remains the best option for patients requiring cystectomy. PMID:18210063

Hautmann, R E

2008-01-01

353

Perioperative substitution of anti-epileptic drugs.  

PubMed

A common problem in brain and abdominal surgery is the perioperative substitution of antiepileptic drugs (AEDs) when patients are temporarily unable to take these drugs orally. We searched the literature for clinical trials with patients or healthy volunteers in whom non-oral formulations of AEDs as substitution were tested. Different search engines, handbooks, expert opinion and our own experience, were used. Pharmaceutical companies were approached for recommendations. This led to three categories of replacement: 1. commercial alternative (n = 10) for clonazepam, diazepam, lacosamide, levetiracetam, lorazepam, midazolam, nitrazepam, phenobarbital, phenytoin, and valproic acid; 2. alternatives that must be prepared (n = 6) for carbamazepine, clobazam, lamotrigine, oxcarbazepine, primidone, topiramate; 3. no alternative (n = 7) for ethosuccimide, felbamate, retigabine, stiripentol, tiagabine, vigabatrin, zonisamide. Thus, for a substantial number of AEDs, unofficial perioperative treatment strategies need to be followed for lack of alternatives to oral administration. There is little clinical research addressing the equivalence of oral and parenteral formulas. Perioperative substitution of AEDs is an underestimated problem, and may increase the risk of postoperative seizures. PMID:23996127

Wichards, Wilma S W; Schobben, Alfred F A M; Leijten, Frans S S

2013-11-01

354

Maternal stress and behavioral adaptation in methadone- or buprenorphine-exposed toddlers.  

PubMed

The current study examined the relationship between early interaction, parenting stress, maternal psychological distress symptoms, and behavior problems and health-related quality of life among children born to mothers in opioid maintenance treatment (OMT) in Norway during the period 2005-2007 (N = 36). This group was compared with a normative sample of mothers without substance abuse problems and their children (N = 36). There were significant group differences (p < .01) in perceived child problems in toddlerhood. In a regression model, mothers' self-reported psychological distress symptoms in terms of depression and anxiety symptoms significantly predicted child behavior problems (p < .01) and health-related quality of life (p < .01) rather than parenting stress. No significant, unique effect of exposure was found after controlling for other factors that could influence developmental outcomes. These findings add to the growing evidence on the importance of maternal psychological well-being for child development, and underscore the need to address opioid-maintained women's personal maladjustment and the constellation of stress experienced by mothers in recovery. PMID:23999378

Sarfi, Monica; Sundet, Jon Martin; Waal, Helge

2013-12-01

355

Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?  

PubMed

The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence. PMID:23145768

Garcia-Portilla, Maria Paz; Bobes-Bascaran, Maria Teresa; Bascaran, Maria Teresa; Saiz, Pilar Alejandra; Bobes, Julio

2014-02-01

356

Improvement in Psychopathology Among Opioid-Dependent Adolescents During Behavioral-Pharmacological Treatment  

PubMed Central

Objective To examine changes in behavioral and emotional problems among opioid-dependent adolescents during a four week combined behavioral and pharmacological treatment. Methods We examined scales of behavioral and emotional problems in youth using the Youth Self Report (YSR) measure at the time of substance abuse treatment intake and changes in scale scores during treatment Participants were 36 adolescents (ages 13–18 eligible) who met DSM-IV criteria for opioid dependence. Participants received a 28-day outpatient, medication-assisted withdrawal with either buprenorphine, or clonidine, as part of a double-blind, double-dummy comparison of these medications. All participants received a common behavioral intervention, composed of three individual counseling sessions per week, and incentives contingent on opioid-negative urine samples (collected three times/week) attendance and completion of weekly assessments. Results: Although a markedly greater number of youth who received buprenorphine remained in treatment relative to those who received clonidine, youth who remained in treatment showed significant reductions during treatment on two YSR grouping scales (Internalizing Problems and Total Problems) and four of the empirically based syndrome scales (Somatic, Social, Attention and Thought). On YSR competence and adaptive scales, no significant changes were observed. There was no evidence that changes in any scales differed across medication condition. Conclusions Youth who were retained demonstrated substantive improvements in a number of clinically meaningful behavioral and emotional problems, irrespective of pharmacotherapy provided to them.

Moore, Sarah K.; Marsch, Lisa A.; Badger, Gary J.; Solhkhah, Ramon; Hofstein, Yariv

2011-01-01

357

Preclinical evaluation of skin substitutes.  

PubMed

The important requirements of a skin substitute such as water vapour permeability, adherence to the excised wound surface, oxygen permeability, mechanical properties, impermeability to micro-organisms and exudate soaking capacity have been highlighted. Two commercial synthetic skin substitutes, Bioclusive and Geliperm, have been used to establish the preclinical assessment procedures for skin substitutes. Two in vitro techniques, the 'Water Cup' and the 'Inverted Cup,' and two in vivo methods involving a 'Ventilated Hygrometer Chamber' system and an Evaporimeter have been employed to assess and compare the water vapour permeability of the skin substitutes under controlled conditions. An Evaporimeter, which is very simple to operate, provides more accurate results. A simple test has been designed to evaluate the early adherence of the skin substitutes to the excised wound surface of rats. The pulling force and the peeling force required to remove the membrane from the wound surface have been measured and these forces have been found to depend upon the composition of the membrane. An oxygen permeability cell has been fabricated which measures the dissolved oxygen permeability of the skin substitutes. The detection of oxygen is based on the electrocatalytic reduction of oxygen at the surface of a noble metal. The tensile properties of the skin substitutes have been measured by an International Standard procedure and both the skin prostheses are associated with some drawbacks. An in vitro method of testing the microbial permeability of the skin substitutes has been designed which simulates an oozing colonized wound that a skin substitute faces in cases of septicaemia. Both the test materials were impermeable to both bacteria and fungi and will provide an effective barrier. The effectiveness of the skin substitutes to absorb wound exudate from the wound surface has been evaluated by soaking the pieces of the membranes in water, plasma and serum and observing their weight gain. The soaking capacity depends upon the composition and nature of the material. The procedures developed have been employed to evaluate a hydrogel type synthetic skin substitute recently formulated in our laboratory. PMID:2275766

Nangia, A; Hung, C T

1990-10-01

358

Iridium-Catalyzed Allylic Substitution  

Microsoft Academic Search

\\u000a \\u000a Abstract  Iridium-catalyzed asymmetric allylic substitution has become a valuable method to prepare products from the addition of nucleophiles\\u000a at the more substituted carbon of an allyl unit. The most active and selective catalysts contain a phosphoramidite ligand\\u000a possessing at least one arylethyl substituent on the nitrogen atom of the ligand. In these systems, the active catalyst is\\u000a generated by a base-induced

John F. Hartwig; Mark J. Pouy

359

Dyscravia: voicing substitution dysgraphia.  

PubMed

We report a new type of dysgraphia, which we term dyscravia. The main error type in dyscravia is substitution of the target letter with a letter that differs only with respect to the voicing feature, such as writing "coat" for "goat", and "vagd" for "fact". Two Hebrew-speaking individuals with acquired dyscravia are reported, TG, a man aged 31, and BG, a woman aged 66. Both had surface dysgraphia in addition to their dyscravia. To describe dyscravia in detail, and to explore the rate and types of errors made in spelling, we administered tests of writing to dictation, written naming, and oral spelling. In writing to dictation, TG made voicing errors on 38% of the words, and BG made 17% voicing errors. Voicing errors also occurred in nonword writing (43% for TG, 56% for BG). The writing performance and the variables that influenced the participants' spelling, as well as the results of the auditory discrimination and repetition tasks indicated that their dyscravia did not result from a deficit in auditory processing, the graphemic buffer, the phonological output lexicon, the phonological output buffer, or the allographic stage. The locus of the deficit is the phoneme-to-grapheme conversion, in a function specialized in the conversion of phonemes' voicing feature into graphemes. Because these participants had surface dysgraphia and were forced to write via the sublexical route, the deficit in voicing was evident in their writing of both words and nonwords. We further examined whether the participants also evinced parallel errors in reading. TG had a selective voicing deficit in writing, and did not show any voicing errors in reading, whereas BG had voicing errors also in the reading of nonwords (i.e., she had dyslegzia in addition to dyscravia). The dissociation TG demonstrated indicated that the voicing feature conversion is separate for reading and writing, and can be impaired selectively in writing. BG's dyslegzia indicates that the grapheme-to-phoneme conversion also includes a function that is sensitive to phonological features such as voicing. Thus the main conclusion of this study is that a separate function of voicing feature conversion exists in the phoneme-to-grapheme conversion route, which may be selectively impaired without deficits in other functions of the conversion route, and without a parallel deficit in reading. PMID:20298704

Gvion, Aviah; Friedmann, Naama

2010-06-01

360

Treatment of polydrug-using opiate dependents during withdrawal: towards a standardisation of treatment  

PubMed Central

Background The growing tendency among opioid addicts to misuse multiple other drugs should lead clinicians and researchers to search for new pharmacological strategies in order to prevent life-threatening complications and minimize withdrawal symptoms during polydrug detoxification. Methods A non-randomised, open-label in-patient detoxification study was used to compare the short-time efficacy of a standardised regimen comprising 6 days Buprenorphine and 10 days Valproate (BPN/VPA) (n = 12) to a control group (n = 50) who took a 10-day traditional Clonidine/Carbamazepine (CLN/CBZ) regimen. Sixty-two dependent subjects admitted to a detoxification unit were included, all dependent on at least opioids and benzodiazepines. Other dependencies were not excluded. Results In the BPN/VPA group, 8 out of 12 patients (67%) completed treatment compared with 25 of 50 patients (50%) in the CLN/CBZ group; this difference between the groups was non-significant (p = 0.15). Withdrawal symptoms were reduced in both groups, but only the BPN/VPA group achieved a reduction in withdrawal symptoms from day one. The difference between the two groups was significantly in favour of the BPN/VPA group for days 2 (p < 0.001), 3 (p < 0.05), 4 (p < 0.001), 5 (p < 0.01), 7 (p < 0.01) and 8 (p < 0.05). The BPN/VPA combination did not affect blood pressure, pulse or liver function, and the total burden of side-effects was experienced as modest. There appeared to be no pharmacological interactions of clinical concern, based on measurement of Buprenorphine and Valproate serum levels. Both the patients and the staff were satisfied with the standardised treatment combination. Conclusion Overall, the combination of Buprenorphine and Valproate seems to be a safe and promising method for treating multiple drug withdrawal symptoms. The results of this study suggest that the BPN/VPA combination is potentially a better detoxification treatment for polydrug withdrawal than the traditional treatment with Clonidine and Carbamazepine. However, a randomised, double-blind study with a larger sample size to confirm our results is recommended. Trial registration Clinical Trials.gov: NCT00367874

Kristensen, ?istein; L?landsmo, Terje; Isaksen, Ase; Vederhus, John-Kare; Clausen, Thomas

2006-01-01

361

Synthesis and electronic structure of proton-type partially substituted birnessite by period-four transition metal  

SciTech Connect

Highlights: {yields} Partial metal substitutions of birnessite result in three types of crystal structure. {yields} Rhombohedral, monoclinic and hexagonal phase emerged in the substituted birnessite. {yields} The electrical conductivity decreased by substitution of transition metal for Mn. {yields} Partially substitution by Fe, Co and Ni poses splitting of crystal field for MnO{sub 6}. -- Abstract: Partially substituted proton-type birnessite were prepared by solid state reaction and their structures were refined. The formed birnessite with no substitution is identified to rhombohedral phase. In the case of substitution treatment by V and Cr for Mn, birnessite phase was not formed. On substituting Fe, hexagonal phase increased with increase of the amount of the Fe. For Co and Ni-substitution, monoclinic phase emerged at substitution ratio of around 0.37 and 0.02, respectively. For the substitution of Cu, only the monoclinic birnessite formed irrespective of the ratio. The electric conductivity of the partially substituted birnessites was examined at room temperature. The general trend is lower conductivity with increasing ratio of contained substituents. On several mol% of the substitution by Ni and Cu, the conductivity slightly increased. From DOS calculation of these compounds, the partially substitution for Mn by Fe, Co and Ni in the birnessite poses splitting of crystal field to emerge new bands at around -1 and +1 eV by Mn(IV) 3d orbital.

Takei, Takahiro, E-mail: takei@yamanashi.ac.jp [Center for Crystal Science and Technology, University of Yamanashi, 7-32 Miyamae, Kofu, Yamanashi 400-8511 (Japan)] [Center for Crystal Science and Technology, University of Yamanashi, 7-32 Miyamae, Kofu, Yamanashi 400-8511 (Japan); Dong, Qiang; Yonesaki, Yoshinori; Kumada, Nobuhiro; Kinomura, Nobukazu [Center for Crystal Science and Technology, University of Yamanashi, 7-32 Miyamae, Kofu, Yamanashi 400-8511 (Japan)] [Center for Crystal Science and Technology, University of Yamanashi, 7-32 Miyamae, Kofu, Yamanashi 400-8511 (Japan)

2011-11-15

362

Point substitutions in Japanese alloalbumins.  

PubMed Central

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. Images

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

1989-01-01

363

Substance Abuse Treatment Facility Locator  

MedlinePLUS

... Health Services Locator Buprenorphine Physician Locator Find a Facility in Your State To locate the drug and ... Service . Privacy Policy . Home | About the Locator | Find Facilities Near You | Find Facilities by City, County, State ...

364

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

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Copper complex of (substituted sulfonaphthyl...Specific Chemical Substances § 721.2577 Copper complex of (substituted sulfonaphthyl...chemical substances identified generically as copper complex of (substituted...

2013-07-01

365

40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...  

Code of Federal Regulations, 2010 CFR

...methyl methacrylate, and substituted silane. 721.6920 Section 721.6920 ...methyl methacrylate, and substituted silane. (a) Chemical substance and significant...methyl methacrylate, and substituted silane (PMN P-91-272) is subject to...

2010-07-01

366

40 CFR 721.9545 - Substituted phenyl azo substituted sulfocarbopolycle, sodium salt.  

Code of Federal Regulations, 2012 CFR

...azo substituted sulfocarbopolycle, sodium salt. 721.9545 Section 721.9545 ...azo substituted sulfocarbopolycle, sodium salt. (a) Chemical substance and significant...azo substituted sulfocarbopolycle, sodium salt (PMN P-96-1263) is subject to...

2012-07-01

367

40 CFR 721.1555 - Substituted phenyl azo substituted benzenediazonium salt.  

Code of Federal Regulations, 2010 CFR

...phenyl azo substituted benzenediazonium salt. 721.1555 Section 721.1555 ...phenyl azo substituted benzenediazonium salt. (a) Chemical substance and significant...phenyl azo substituted benzenediazonium salt (PMN P-92-652) is subject to...

2010-07-01

368

[Hyalomatrix PA(®) in skin substitutes. About 10 cases].  

PubMed

During the surgical treatment of burns and reconstructive surgery, we can use autografts, allografts, xenografts or dermal substitutes. Acellular dermal substitutes, implantable medical devices of class III are composed mostly of collagen but also, more recently, derivatives of hyaluronic acid (Hyalomatrix PA(®)). Their mechanism of action is based on revascularization and colonization by fibroblasts of the patient. They are then used to screen for delayed epidermal grafting (2-stage procedure for Integra(®), Matriderm(®) 2mm, Renoskin(®), Hyalomatrix PA(®)) or simultaneous (1-time procedure for IntegraSL(®), Matriderm(®) 1mm). We report 10 cases of clinical use of Hyalomatrix PA(®) in the service of burns and plastic surgery of Nantes. PMID:21106288

Perrot, P; Dellière, V; Brancati, A; Duteille, F

2011-04-01

369

Magnetic properties of NiZr substituted barium ferrite  

NASA Astrophysics Data System (ADS)

Single-domain fine particles of NiZr substituted barium ferrite has been synthesized by citrate gel route. The magnetization value obtained are comparable with those observed in Co-Ti substitution. This has been attributed to strong preference of Ni2+ for octahedral coordination, and no particular preference for Zr4+ ion. Phase formation at lower temperature permits easy control over the microstructure and hence, a large variation in coercivity (180-4500 Oe) has been possible as a function of x and heat treatment temperature.

Rane, Manisha V.; Bahadur, D.; Kulkarni, S. D.; Date, S. K.

1999-05-01

370

Magnetic properties of NiZr substituted barium ferrite  

NASA Astrophysics Data System (ADS)

Single-domain fine particles of NiZr substituted barium ferrite has been synthesized by citrate gel route. The magnetization value obtained are comparable with those observed in Co-Ti substitution. This has been attributed to strong preference of Ni 2+ for octahedral coordination, and no particular preference for Zr 4+ ion. Phase formation at lower temperature permits easy control over the microstructure and hence, a large variation in coercivity (180-4500 Oe) has been possible as a function of x and heat treatment temperature.

Rane, Manisha V.; Bahadur, D.; Kulkarni, S. D.; Date, S. K.

371

FRICTION SOUNDS FOR SENSORY SUBSTITUTION  

Microsoft Academic Search

This paper explores the use of a physics-based sound model of continuous contact for auditory display in interactive set- tings. An audio-visual interactive display is developed in which the sound model is controlled by the user's gestures. The display is used to investigate to what extent audition can substitute for haptic feedback in conveying perception of inertial properties of a

Federico Avanzini; Davide Rocchesso; Stefania Serafin

372

17O NMR studies on 4- and 4'-substituted chalcones and p-substituted ?-nitrostyrenes  

NASA Astrophysics Data System (ADS)

The 17O NMR chemical shift data for 17O-enriched 4- and 4'-chalcones in toluene at 90°C and for p-substituted ?-nitrostyrenes (natural abundance) in acetonitrile at 70°C are reported. The SCS (substituent chemical shift) range for the 4-chalcones p-CH 3O to p-NO 2 is 16.3 ppm; the range for the 4'-chalcones p-CH 3O to p-NO 2 is 32.4 ppm. The SCS range for the p-substituted-?-nitrostyrenes p-CH 3O to p-NO 2 is 13.2 ppm. The data for the three series gave good correlations with ? + constants, while the Dual Substitutent Parameter treatment only slightly improved the correlations using ? R+ constants. Plots of the 17O chemical shifts for both 4- and 4'-chalcones with 17O data for acetophenones and correlation of 17O chemical shift data for the ?-nitrostyrenes with that of nitrobenzenes gave good correlations. Plots of the 17O data for all the three series with their respective functional group stretching frequencies gave fair correlations.

Boykin, D. W.; Baumstark, A. L.; Balakrishnan, P.; Perjéssy, A.; Hrnc˜iar, P.

373

Synthesis and Evaluation of Three Structurally Related (18)F-Labeled Orvinols of Different Intrinsic Activities: 6-O-[(18)F]Fluoroethyl-diprenorphine ([(18)F]FDPN), 6-O-[(18)F]Fluoroethyl-buprenorphine ([(18)F]FBPN), and 6-O-[(18)F]Fluoroethyl-phenethyl-orvinol ([(18)F]FPEO).  

PubMed

We report the synthesis and biological evaluation of a triplet of 6-O-(18)F-fluoroethylated derivatives of structurally related orvinols that span across the full range of intrinsic activities, the antagonist diprenorphine, the partial agonist buprenorphine, and the full agonist phenethyl-orvinol. [(18)F]fluoroethyl-diprenorphine, [(18)F]fluoroethyl-buprenorphine, and [(18)F]fluoroethyl-phenethyl-orvinol were prepared in high yields and quality from their 6-O-desmethyl-precursors. The results indicate suitable properties of the three 6-O-(18)F-fluoroethylated derivatives as functional analogues to the native carbon-11 labeled versions with similar pharmacological properties. PMID:24933507

Schoultz, Bent W; Hjørnevik, Trine; Reed, Brian J; Marton, János; Coello, Christopher S; Willoch, Frode; Henriksen, Gjermund

2014-06-26

374

Syntheses and antimalarial activities of N-substituted 11-azaartemisinins.  

PubMed

A two-step reaction sequence between artemisinin and methanolic ammonia followed by treatment with Amberlyst 15 yielded 11-azaartemisinin in 65% yield. Substituting a variety of primary alkyl- and heteroaromatic amines for ammonia in the reaction sequence yields N-substituted 11-azaartemisinins in similar or greater yield. When Amberlyst 15 is replaced by a mixture of sulfuric acid/silica gel, both 11-azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin, are formed in 45% and 15% yields, respectively. In vitro and in vivo test data for a number of novel N-substituted 11-azaartemisinins, against drug-resistant strains of Plasmodium falciparum, show they possess antimalarial activities equal to or greater than that of artemisinin. The most active derivative, N-(2'-acetaldehydo)-11-azaartemisinin, 17, was 26 times more active in vitro and 4 times more active in vivo than artemisinin. PMID:8544181

Torok, D S; Ziffer, H; Meshnick, S R; Pan, X Q; Ager, A

1995-12-22

375

Development and Clinical Evaluation Synthetic Skin Substitute as a Model of Skin Function.  

National Technical Information Service (NTIS)

Temporary skin substitutes, including human cadaver cutaneous allografts, porcine cutaneous xenografts, and amniotic membranes have become widely used in the treatment of thermally injured patients. The principal use of these biologic dressings is for tem...

N. S. Levine A. D. Mason B. A. Pruitt

1983-01-01

376

76 FR 60359 - Phytosanitary Treatments; Location of and Process for Updating Treatment Schedules; Technical...  

Federal Register 2010, 2011, 2012, 2013

...did not retain text explaining that irradiation can be used as a substitute for other...freeze treatment, heat treatment, and irradiation treatment, respectively. Where these...paragraph (h)(1) stated that irradiation treatment in accordance with part...

2011-09-29

377

Skin Substitutes with Improved Barrier Function.  

National Technical Information Service (NTIS)

The present invention relates to in vitro cultured skin substitutes, and in particular to in vitro cultured skin substitutes that have improved barrier function. In some embodiments, improved barrier function is a result of improved culture conditions, wh...

A. Comer L. A. Hoffmann M. Hoffmann

2005-01-01

378

40 CFR 721.1643 - Benzenesulfonic acid, amino substituted phenylazo-.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Benzenesulfonic acid, amino substituted phenylazo-. 721... § 721.1643 Benzenesulfonic acid, amino substituted phenylazo-. ...generically as a benzenesulfonic acid, amino substituted phenylazo-...

2013-07-01

379

Generic substitution of antiepileptic drugs  

PubMed Central

Summary Generic substitution of antiepileptic drugs remains a controversial area without a clear consensus to guide clinicians. The US Food and Drug Administration (FDA) requires rigorous testing of generic products and states that all approved products are interchangeable. FDA studies involve single doses in normal subjects so may not represent the performance of generic products in people with epilepsy. Physician surveys, case reports, and retrospective pharmacy database analyses suggest that antiepileptic drug generic substitution is associated with more health problems and high switchback rates, but these studies have insufficient detail on seizure control and blood levels. Several ongoing prospective randomized trials with rigorous pharmacokinetic methods aim to provide more data for decision-making.

2013-01-01

380

Expectations and Experiences of Substitute Teachers  

ERIC Educational Resources Information Center

This article explores the expectations of support for and the experiences of substitute teachers in an urban school division in Saskatchewan. Data were collected in semistructured interviews with seven substitute teachers. The purpose of the study was to explore how substitute teachers frame their professional experiences and construct their roles…

Duggleby, Patricia; Badali, Sal

2007-01-01

381

On Explicit Substitution with Names  

Microsoft Academic Search

This paper recounts the origins of the ?x family of calculi of explicit substitution with proper variable names, including\\u000a the original result of preservation of strong ?-normalization based on the use of synthetic reductions for garbage collection. We then discuss the properties of a variant\\u000a of the calculus which is also confluent for “open” terms (with meta-variables), and verify that

Kristoffer H. Rose; Roel Bloo; Frédéric Lang

2012-01-01

382

Cationic substitution in tricalcium aluminate  

SciTech Connect

Cubic and orthorhombic crystals of tricalcium aluminate doped with Na{sub 2}O, Fe{sub 2}O{sub 3} and SiO{sub 2} were prepared and examined using an electron probe microanalyzer. The cationic ratios based on six oxygen atoms were derived from the oxide compositions. These data, together with those in previous studies for clinker aluminates containing Mg{sup 2+} and K{sup +}, provided excellent correlations between Al+Fe and Si (Al+Fe=2.001-1.03Si) and Ca+Mg and Na+K+Si [Ca+Mg=3.006-0.51(Na+K+Si)]. The chemical variation that is constrained by these equations is well accounted for by the general formula (Na,K){sub 2x}(Ca,Mg){sub 3-x-y}[(Al,Fe){sub 1-y}Si{sub y}]{sub 2}O{sub 6}, where x is the amount of Ca substituted by Na and K (0{<=}x<0.158), and y is the amount of Al substituted by Si (0{<=}y<0.136). The crystal system changed from cubic to orthorhombic with increasing x value. The substitution of Si and Fe for Al extended the solid solution range of the orthorhombic phase to lower values of x, while its effect on the solid solution range of the cubic phase was reversed.

Fukuda, Koichiro; Inoue, Shinji; Yoshida, Hideto

2003-11-01

383

Iridium-Catalyzed Allylic Substitution  

NASA Astrophysics Data System (ADS)

Iridium-catalyzed asymmetric allylic substitution has become a valuable method to prepare products from the addition of nucleophiles at the more substituted carbon of an allyl unit. The most active and selective catalysts contain a phosphoramidite ligand possessing at least one arylethyl substituent on the nitrogen atom of the ligand. In these systems, the active catalyst is generated by a base-induced cyclometalation at the methyl group of this substituent to generate an iridium metalacycle bound by the COD ligand of the [Ir(COD)Cl]2 precursor and one additional labile dative ligand. Such complexes catalyze the reactions of linear allylic esters with alkylamines, arylamines, phenols, alcohols, imides, carbamates, ammonia, enolates and enolate equivalents, as well as typical stabilized carbon nucleophiles generated from malonates and cyanoesters. Iridium catalysts for enantioselective allylic substitution have also been generated from phosphorus ligands with substituents bound by heteroatoms, and an account of the studies of such systems, along with a description of the development of iridium catalysts is included.

Hartwig, John F.; Pouy, Mark J.

384

Resonant photodissociation in substituted benzenes  

NASA Astrophysics Data System (ADS)

Cyclic aromatic molecules are abundant in organic chemistry, with a wide variety of applications, including pharmacology, pollution studies and genetic research. Among the simplest of these molecules is benzene (C6H6), with many relevant molecules being benzene-like with a single atomic substitution. In such a substitution, the substituent determines a characteristic perturbation of the electronic structure of the molecule. We discuss the substitution of halogens into the ring (C6H5X), and its effects on the dynamics of ionization and dissociation of the molecule without the focal volume effect [1]. In particular, using 800-nm, 50-fs laser pulses, we present results in the dissociation of fluorobenzene, chlorobenzene, bromobenzene and iodobenzene into the phenyl ring (C6H5) and the atomic halogen, and the subsequent ionization of these fragments. The impact of the ``heavy atom effect'' on a ^1(?,?*) -> ^3(n,?*) singlet-triplet intersystem crossing will be emphasized. Currently under investigation is whether such a dissociation can be treated as an effective source of the neutral substituent.[4pt] [1] J. Strohaber and C. Uiterwaal, Phys. Rev. Lett. 100 023002 (2008).

Scarborough, Tim; McAcy, Collin; Foote, David; Uiterwaal, Cornelis

2011-06-01

385

40 CFR 721.267 - N-[2-[(substituted dinitrophenyl)azo]diallylamino-4- substituted phenyl] acetamide (generic name).  

Code of Federal Regulations, 2010 CFR

...dinitrophenyl)azo]diallylamino-4- substituted phenyl] acetamide (generic...dinitrophenyl)azo]diallylamino-4- substituted phenyl] acetamide (generic...dinitrophenyl)azo]diallylamino-4-substituted phenyl]...

2010-07-01

386

Photocatalytic and Antibacterial Activity of Titanium, Fluorine and Silver Co-Substituted Hydroxyapatite  

NASA Astrophysics Data System (ADS)

Synthetic hydroxyapatite (HA), an analogue of the mineral component of bone tissue has been widely used in medicine as bone replacing material. To impart specific properties, HA can be chemically modified by anionic and cationic substitutions during synthesis. Thus the present study was focused in synthesizing nanocrystalline Ti, Ag and F co-substituted HA by microwave synthesis. The prepared powders were characterized by XRD and FTIR for their crystal size, cystallinity and functional groups respectively. XRD spectra reveal that crystal size of prepared powders was in the range of 21-25 nm in as synthesized condition and 45-51 nm in 900 ?C heat-treated condition. Complete decomposition of HA to tri calcium phosphate was observed for Ti substituted HA powder after heat-treatment. Addition of F improved the thermal stability of Ti substituted HA as indicated by predominant phase of HA after heat-treatment. The photocatalytic activity of co-substituted HA powders was examined by degradation of methylene blue (5 × 10-5 M concentration) under visible light irradiation and the results were compared with pure HA. The degradation efficiency of co-substituted HA with respect to methylene blue was twice as high as that of pure HA. Ti and Ag has improved the visible light photocatalytic activity of HA, further F co-substitution has not affected the photocatalytic activity of substituted HA. The antibacterial effect of prepared powders was observed against 1 × 105 cells/mL of Escherichia coli using spread plate method at 24 h incubation period. Ag co-substituted HA showed complete inhibition of growth of Escherichia coli. Thus, among Ti, Ti-F, Ti-F-Ag substituted HA powders, Ti-F-Ag co-substituted HA with excellent visible light photocatalytic activity and anti-bacterial property is expected to be a potential candidate for biomedical applications.

Sandhyarani, M.; Rameshbabu, N.; Venkateswarlu, K.; Ravisankar, K. V.; Ashok, M.; Anandan, S.

387

Study of a tissue equivalent gelatine based tissue substitute.  

National Technical Information Service (NTIS)

A study of several tissue substitutes for use as volumetric dosimeters was performed. The tissue substitutes studied included tissue substitutes from previous studies and from ICRU 44. The substitutes were evaluated for an overall match to Reference Man w...

J. L. Spence

1992-01-01

388

Mobile opioid agonist treatment and public funding expands treatment for disenfranchised opioid-dependent individuals.  

PubMed

The New Jersey Medication Assisted Treatment Initiative (NJ-MATI) sought to reduce barriers to treatment by providing free, opioid agonist treatment (OAT, methadone or buprenorphine) via mobile medication units (MMUs). To evaluate barriers to OAT, logistic regression was used to compare opioid dependent patients enrolled in NJ-MATI to those entering treatment at fixed-site methadone clinics or non-medication assisted treatment (non-MAT). Client demographic and clinical data were taken from an administrative database for licensed treatment providers. The MMUs enrolled a greater proportion of African-American, homeless, and uninsured individuals than the fixed-site methadone clinics. Compared to non-MAT and traditional methadone clients, NJ-MATI patients were more likely to be injection drug users and daily users but less likely to have a recent history of treatment. These observations suggest that the patient-centered policies associated with NJ-MATI increased treatment participation by high severity, socially disenfranchised patients who were not likely to receive OAT. PMID:24468235

Hall, Gerod; Neighbors, Charles J; Iheoma, Jude; Dauber, Sarah; Adams, Merribeth; Culleton, Robert; Muench, Fred; Borys, Suzanne; McDonald, Rebecca; Morgenstern, Jon

2014-04-01

389

Solidphase synthesis of substituted 1,2,3-triazoles  

Microsoft Academic Search

Diversely substituted 1,2,3-triazoles have been synthesized on a solid support. A resin-bound 3-oxobutyramide could be effectively condensed with primary aliphatic amines. The resulting 3-amino-2-butenoic acid amides were then cyclized by treatment with tosyl azide in the presence of a tertiary amine. Acidolytic cleavage from the support yielded the corresponding 1,2,3-triazoles in purities up to 82% (HPLC).

Florencio Zaragoza; Susanne Vejle Petersen

1996-01-01

390

Identification of Biased Amino Acid Substitution Patterns in Human Immunodeficiency Virus Type 1 Isolates from Patients Treated with Protease Inhibitors  

Microsoft Academic Search

Human immunodeficiency virus type 1 (HIV-1) amino acid substitutions observed during antiretroviral drug therapy may be caused by drug selection, non-drug-related evolution, or sampling error introduced by the sequencing process. We analyzed HIV-1 sequences from 371 untreated patients and from 178 patients receiving a single protease inhibitor. Amino acid substitution patterns during treatment were compared with inferred substitution patterns arising

ROBERT W. SHAFER; PHILLIP HSU; AMY K. PATICK; CHARLES CRAIG; VOLKER BRENDEL

1999-01-01

391

Sensory substitution as an artificially acquired synaesthesia.  

PubMed

In this review we explore the relationship between synaesthesia and sensory substitution and argue that sensory substitution does indeed show properties of synaesthesia. Both are associated with atypical perceptual experiences elicited by the processing of a qualitatively different stimulus to that which normally gives rise to that experience. In the most common forms of sensory substitution, perceptual processing of an auditory or tactile signal (which has been converted from a visual signal) is experienced as visual-like in addition to retaining auditory/tactile characteristics. We consider different lines of evidence that support, to varying degrees, the assumption that sensory substitution is associated with visual-like experiences. We then go on to analyse the key similarities and differences between sensory substitution and synaesthesia. Lastly, we propose two testable predictions: firstly that, in an expert user of a sensory substitution device, the substituting modality should not be lost. Secondly that stimulation within the substituting modality, but by means other than a sensory substitution device, should still produce sensation in the normally substituted modality. PMID:22885223

Ward, Jamie; Wright, Thomas

2014-04-01

392

Introduction of low dose transdermal buprenorphine -- did it influence use of potentially addictive drugs in chronic non-malignant pain patients?  

PubMed

The aim was to study the introduction of the new low dose transdermal buprenorphine (LD-TD-BUP) in Norway, particularly with regard to former use and co-medication with other potentially addictive drugs. The nationwide Norwegian Prescription Database contains information on all prescription drugs dispensed to individual non-institutionalised patients, and we may follow all individuals who received LD-TD-BUP (Norspan) after marketing on the Norwegian market on 15/11/05. We studied all prescriptions of opioids and other potentially addictive drugs to patients receiving at least two LD-TD-BUP prescriptions during 2004-2006. Poisson regressions were run with concomitant use of addictive drugs (yes, no) as the endpoint. Overall, 1884, non cancer individuals received at least two prescription of LD-TD-BUP. Of these 91.7% received prescriptions of other opioids and 58.6% of them had also been prescribed benzodiazepines/carisoprodol before the prescription of LD-TD-BUP. Of the LD-TD-BUP users who received more than one prescription, 60% co-medicated with at least one other potentially addictive drug, and 24% with at least two. In the multivariate analysis, the variables associated with a higher likelihood of using co-medicated drugs were: previous use of benzodiazepines/carisoprodol relative risk RR=16.7 (95% CI 10.4-26.9), previous use of opioids RR=4.0 (1.9-8.7) and younger age 20-40 years RR=1.9 (1.6-2.3). So far, it is questionable whether the introduction of LD-TD-BUP actually has stabilised opioids consumption or whether it has complicated and increased the consumption of potentially addictive drugs. PMID:19095476

Skurtveit, Svetlana; Furu, Kari; Kaasa, Stein; Borchgrevink, Petter C

2009-10-01

393

Exfoliation and thermal transformations of Nb-substituted layered titanates  

SciTech Connect

Single-layer Nb-substituted titanate nanosheets of ca. 1 nm thickness were obtained by exfoliating tetrabutylammonium (TBA)-intercalated Nb-substituted titanates in water. AFM images and turbidity measurements reveal that the exfoliated nanosheets crack and corrugate when sonicated. Upon heating, the thermal transformation into anatase and further to rutile is retarded. This suppression of the phase transition upon higher valent substitution may promote technological applications of anatase thin films, hereunder development of films with TCO properties. Depending on the oxygen partial pressure during the transformation, the Nb-substitution into TiO{sub 2} provokes different defect situations and also electronic properties. At reducing conditions, Nb is incorporated as Nb{sup V} and an equivalent amount of Ti{sup IV} is transformed to Ti{sup III} as evidenced by XPS. Magnetic susceptibility data show accordingly paramagnetic behavior. For samples heated in air Ti{sup IV} and Nb{sup V} cations prevail, the latter is compensated by cation vacancies. {sup 93}Nb MAS NMR data prove that Nb is finely dispersed into the transformed (Ti,Nb)O{sub 2} oxide matrices without sign of Nb{sub 2}O{sub 5} (nano)precipitates. The Nb-O-Ti bonds and defects at cation sites are considered key factors for increasing the transformation temperatures for conversion of the nanosheets to anatase and finally into rutile. It is further tempting to link the delay in crystallization to morphology limitations originating from the nanosheets. The present work shows that layered Nb-titanates are appropriate precursors for formation of highly oriented Nb-substituted anatase thin films via delamination, reconstruction and subsequent heat treatment. - Graphical abstract: Layered Nb-titanates are appropriate precursors for formation of highly oriented Nb-substituted anatase thin films via delamination, reconstruction and subsequent heat treatment. Highlights: Black-Right-Pointing-Pointer Single layer Nb-substituted nanosheets were obtained by exfoliation of layered titanates. Black-Right-Pointing-Pointer Nb(V) successfully introduced into anatase and rutile solid solutions. Black-Right-Pointing-Pointer Anatase obtained from reconstructed nanosheets exhibit enhanced thermal stability. Black-Right-Pointing-Pointer Oxygen partial pressure influences the valence of Nb in heat-treated samples. Black-Right-Pointing-Pointer Deposition of oriented thin Ti(Nb)O{sub 2} layers by spray coating was demonstrated.

Song Haiyan; Sjastad, Anja O.; Fjellvag, Helmer; Okamoto, Hiroshi [Department of Chemistry and Centre for Materials Science and Nanotechnology, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo (Norway); Vistad, Ornulv B.; Arstad, Bjornar [SINTEF Materials and Chemistry, P.O. Box 124, Blindern, N-0314 Oslo (Norway); Norby, Poul, E-mail: pnor@risoe.dtu.dk [Department of Chemistry and Centre for Materials Science and Nanotechnology, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo (Norway); Materials Research Division, Riso National Laboratory for Sustainable Energy, Technical University of Denmark, P.O. Box 49, DK-4000 Roskilde (Denmark)

2011-12-15

394

Association between risk behaviors and antiretroviral resistance in HIV-infected patients receiving opioid agonist treatment  

PubMed Central

Objectives Antiretroviral (ARV) resistance is of concern. Opioid agonist treatment ( i.e., methadone or buprenorphine) is effective and decreases HIV transmission risk behaviors and HIV seroconversion. Despite prevention efforts, injection drug use (IDU) and risky sexual behaviors remain prevalent in patients receiving opioid agonist treatment. The purpose of this study is to determine in HIV-infected patients receiving opioid agonist treatment, the prevalence of HIV transmission risk behaviors, the prevalence of ARV resistance, and the prevalence of ARV resistance among those with risk behaviors. Methods The design was a cross-sectional, study of patients recruited from opioid treatment programs and outpatient practices. We measured demographic, drug treatment, and HIV clinical information (including ARV adherence), self-reported HIV risk behaviors and drug use, urine toxicologies, and genotype testing for ARV resistance (with both standard assays and Ultradeep sequencing). Data analysis included descriptive statistics. Results 59 subjects enrolled. 64% were male, 24% were white, and mean age was 46 years. 53% were receiving methadone and 47% buprenorphine. 80% were on opioid agonist treatment for 12 weeks or more. 14% reported unprotected sex, 7% reported sharing needles or works, and 60% had positive urine toxicology for illicit drug use. 15% had evidence of HIV resistance by standard genotyping, 7% with single class resistance, 3% with double class resistance, and 5% with triple class resistance. Ultradeep sequencing found additional class resistance in 5 subjects. 22% of subjects with evidence of transmission risk behaviors vs. 14% of subjects without risk behaviors had evidence of ARV resistance. Conclusions Improved prevention and treatment efforts may be needed for HIV-infected, opioid dependent individuals receiving opioid agonist treatment to decrease transmission of ARV resistant virus, especially in resource limited settings.

Tetrault, Jeanette M.; Kozal, Michael J.; Chiarella, Jennifer; Sullivan, Lynn E.; Dinh, An T; Fiellin, David A.

2013-01-01

395

Tolerance to the mydriatic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine in mice  

Microsoft Academic Search

An increase in the use of opioid derivatives in the treatment of pain syndrome in clinical practice, and especially in the\\u000a treatment of cancer, has added impetus to the search for an agent which does not induce tolerance and cross-tolerance to other\\u000a opiodis. The mydriatic effect of opioids in mice, the correlation between analgesia and mydriasis, and tolerance to the

Mohammed Kaadan; Anatoli Stav; Ruth Rabinowitz; Sara Shavit; Amos D. Korczyn

1994-01-01

396

[Without Title  

Microsoft Academic Search

.   \\u000a Rationale: Buprenorphine is an opioid agonist–antagonist used in the treatment of opioid dependence. Naloxone has been combined with\\u000a buprenorphine to decrease the parenteral abuse potential of buprenorphine. This addition of naloxone may also confer further\\u000a opioid blockade efficacy. Objectives: To test the opioid blockade efficacy of sublingual buprenorphine\\/naloxone versus buprenorphine alone and determine whether:\\u000a (1) the blockade efficacy of

Eric C. Strain; Sharon L. Walsh; George E. Bigelow

2002-01-01

397

Dihalo-substituted dibenzopentalenes: their practical synthesis and transformation to dibenzopentalene derivatives.  

PubMed

Diiodo- and bromo, iodo-substituted dibenzopentalenes were obtained by treatment of 5,6,11,12-tetradehydrodibenzo[a,e]cyclooctene with I(2) and IBr, respectively. These dihalo-substituted pentalenes reacted with terminal ethynes in Sonogashira coupling and with arylboronic acid in Suzuki-Miyaura coupling to give a series of phenylethynyl- and/or aryl-substituted pentalenes. Suzuki-Miyaura coupling of the halopentalenes with in situ prepared pentaleneboronic esters provided bis-, tri-, and tetra(dibenzopentalene)s. It was found that these dibenzopentalene oligomers underwent facile electrochemical reduction and exhibited a bathochromic shift in UV-vis absorption spectra because of their expanded ?-systems. PMID:22799261

Xu, Feng; Peng, Lifen; Orita, Akihiro; Otera, Junzo

2012-08-01

398

From thioether substituted porphyrins to sulfur linked porphyrin dimers: an unusual SNAr via thiolate displacement?  

PubMed

Treatment of meso 2-ethylhexyl-3-mercaptopropionate substituted porphyrins with base at room temperature generated a porphyrin thiolate anion which in situ reacted in a nucleophilic aromatic substitution (SNAr) reaction with remaining thioether derivative. This reaction yielded S-linked bisporphyrins in good yields, with mechanistic insight obtained via displacement reactions. Additionally, SNAr of the thioether chain was achieved using S- and organolithium nucleophiles. PMID:24247987

Ryan, Aoife A; Plunkett, Shane; Casey, Aoife; McCabe, Thomas; Senge, Mathias O

2014-01-11

399

Activation of Peroxisome Proliferator-Activated Receptor   by Substituted Urea-Derived Soluble Epoxide Hydrolase Inhibitors  

Microsoft Academic Search

Soluble epoxide hydrolase (sEH) plays a major role in regulating vascular epoxyeicosatrienoic acid metabolism and function, and substituted urea derivatives that inhibit sEH activity reduce blood pressure in hypertensive rats. We found that substituted urea derivatives containing a dodecanoic acid group, besides effectively inhibiting sEH, increased peroxisome proliferator- activated receptor (PPAR) activity. In PPAR transfected COS-7 cells, treatment with 10

Xiang Fang; Shanming Hu; Takaho Watanabe; Neal L. Weintraub; Gary D. Snyder; Jianrong Yao; Yi Liu; John Y.-J. Shyy; Bruce D. Hammock; Arthur A. Spector

2005-01-01

400

Synthesis of 2-substituted-7-azaindoles from 2-amino-3-picolin  

Microsoft Academic Search

An easy route to the synthesis of 2-substituted-7-azaindole derivatives has been developed. The carbinol intermediate dissolved in DMF undergoes cyclization upon treatment with sodium hydride, trifluoroacetic anhydride, and trifluoroacetic acid at 120°C in a straightforward and one-pot step. An alternative methodology using (CF3SO2)2O in acetonitrile in basic media followed by the addition of CF3COOH affords the expected 2-substituted azaindole in

Javier Parcerisa; Manel Romero; Maria Dolors Pujol

2008-01-01

401

Use of plasma volume substitutes and plasma in developing countries*  

PubMed Central

Plasma and plasma substitutes are used in the treatment of various conditions such as haemorrhage and shock. This article examines the role of crystalloids, artificial colloids, human plasma, human albumin, and plasma protein fraction, in the treatment of such patients, with particular reference to peripheral health facilities in developing countries. It is concluded that 0.9% saline, together with 5-6% dextrose, is of particular importance in this situation since it is easy to produce locally, is stable at high temperatures, and has a low cost/benefit ratio. The second priority is to ensure the availability of a limited quantity of one or more colloid plasma substitutes. In the field of plasma, fresh frozen or fresh liquid plasma is most useful for the treatment of various haemostatic derangements and follow-up treatment of severe burns, since it contains the widest spectrum of therapeutically useful components and can be produced locally with an acceptable degree of difficulty. The treatment of severe diarrhoea with special alkaline electrolyte solutions and oral rehydration solutions is also outlined.

Lundsgaard-Hansen, P.; Collins, J. A.; David-West, A. S.; Lopez, C. G.; Hantchef, Z. S.; Lothe, F.; von Steffens, E.