RESEARCH ARTICLE Opioid plasma concentrations in methadone- and buprenorphine-maintained patients REINHOLD JAGSCH 1 , WOLFGANG GOMBAS 2 , SHIRD-DIETER SCHINDLER 3 , HARALD EDER 3 , DAVID E. MOODY 4 & GABRIELE FISCHER 3 1 Faculty of Psychology, Clinical and Health Psychology, University of Vienna, Vienna, Austria, 2 Department of Social Psychiatry, University Hospital of Vienna, Vienna, Austria, 3 Department of General Psychiatry, University Hospital of Vienna, Vienna, Austria, and 4 Center for Human Toxicology, University of Utah, Salt Lake City, UT, USA Abstract This is the first trial to compare the relationship of opioid plasma concentrations in methadone- versus buprenorphine-maintained subjects. Sixty subjects (19 females and 41 males) seeking treatment who met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were recruited and treated at the Drug Addiction Outpatient Clinic at the University of Vienna. Of these, 44 (11 female and 33 male) were included in the analyses of plasma concentrations. Subjects received either daily sublingual buprenorphine (2 mg or 8 mg tablets; maximum daily dose: 8 mg) or oral methadone (racemic R-/S-methadone) and were maintained on a stable dose after an induction period of 2 weeks. Mean dose and mean plasma concentrations were correlated on an individual and collective basis. Correlation was 0.51 for buprenorphine, whereas the score for methadone was 0.69. Intra-individual variation was much higher for buprenorphine (p 5 0.0001), while the concentration-to-dose ratio was very small. Based on the differences of the pharmacokinetics of blood plasma of the two agents, we tried to explain the differences in the acceptance of treatment, which was significantly lower in the buprenorphine-maintained group. No such differences could be evaluated between completers and dropouts in buprenorphine-maintained subjects, neither concerning withdrawal scores nor dose, plasma concentration, concentration-to-dose ratios or intra-individual variation. Introduction Buprenorphine, a semi-synthetic partial m-receptor agonist and a k-receptor antagonist, was first considered in 1978 as a potential agent for opioid-maintenance therapy, due to its long-lasting opioid-agonist effects such as analgesia, euphoria and sedation (Jasinski et al., 1978). In addition, a dose-related plateau effect was observed for buprenophine on subjective measures and respiratory depression, one of the most common fatal effects of heroin overdose (Walsh et al., 1994). When taken sublingually bioavailability is 35%, with a half-life of approximately 7 hours, and a reported duration of action of up to 72 hours (Bullingham et al., 1982). Peak plasma concentra- tion is reached after about 1 hour and the first effects can be observed after approximately 20 minutes (Chiang & Hawks, 2003). Buprenorphine is considered useful in maintenance therapy due to: (i) a slow increase in plasma concentration, which reduces the risk of respiratory depression; (ii) a relatively low degree of induced euphoria; (iii) a capacity to block the effects of other opioid agonists; and (iv) a low rate of withdrawal symptoms on discontinuation, even if withdrawal is sudden (Nutt, 1997). In this study, buprenorphine was compared with standard treatment using methadone, the only substance authorized originally when oral opioid maintenance therapy was first introduced in Austria in 1987. In this country, methadone (which was first dispensed for maintenance in the United States in 1965; Dole & Nyswander, 1965) is administered as racemic 50% R- and 50% S-methadone, in the form of an oral sugar solution to avoid intravenous application. However, the use of methadone is limited due to its side effects (especially regarding long-term administration) including weight gain (often in the form of leg oedemas as a sign of water Correspondence to: Reinhold Jagsch, PhD, Faculty of Psychology, Clinical and Health Psychology, University of Vienna, Universita ¨tsstraße 7/6th floor, 1010 Vienna, Austria. Tel: þ43 1 4277/478 94; Fax: þ43 1 4277/478 99; E-mail: reinhold.jagsch@univie.ac.at Addiction Biology (December 2005) 10, 365 – 371 ISSN 1355-6215 print/ISSN 1369-1600 online/05/040365–07 ª Society for the Study of Addiction to Alcohol and Other Drugs Taylor & Francis DOI: 10.1080/13556210500358441