title: Open-label dose-finding trial of buprenorphine implants (Probuphine) for treatment of heroin dependence.
abstract: Buprenorphine, a mu-opioid receptor partial agonist, has been shown to be safe and effective for treatment of opioid dependence. A novel implantable formulation of buprenorphine (Probuphine), using a polymer matrix sustained-release technology, has been developed to offer treatment for opioid dependence while minimizing risks of patient noncompliance and illicit diversion. The goal of the current study was to conduct an initial, open-label, evaluation of the safety, pharmacokinetics, and efficacy of two doses of Probuphine in subjects with opioid dependence maintained on sublingual buprenorphine. Two doses of Probuphine were evaluated in 12 heroin-dependent volunteers switched from daily sublingual buprenorphine dosing to either two or four Probuphine implants based upon their buprenorphine daily maintenance dose of 8 mg or 16 mg respectively, and were monitored for 6 months. Probuphine implants provided continuous steady state delivery of buprenorphine until their removal at 6 months. Withdrawal symptoms and craving remained low throughout the 6 months. For the 12 subjects, an average of 59% of urines were opioid-negative across the 6 month treatment period. Injection site reactions were present in half of patients, but none were serious. No safety concerns were evident. These results suggest that Probuphine implants offer significant promise for enhancing delivery of effective opioid substitution treatment while minimizing risk for abuse of medication.
authors.affiliation: Discipline of Pharmacology, University of Adelaide, Adelaide, SA 5005, Australia. jason.white@adelaide.edu.au
authors.forename: Jason
authors.initials: J
authors.lastname: White
authors.forename: James
authors.initials: J
authors.lastname: Bell
authors.forename: John B
authors.initials: JB
authors.lastname: Saunders
authors.forename: Paul
authors.initials: P
authors.lastname: Williamson
authors.forename: Maria
authors.initials: M
authors.lastname: Makowska
authors.forename: Aaron
authors.initials: A
authors.lastname: Farquharson
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Beebe
mesh_terms: D000286:Administration, Sublingual; D000293:Adolescent; D000328:Adult; D002047:Buprenorphine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use* / Q000652:urine; D004343:Drug Implants; D005260:Female; D006556:Heroin Dependence / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000097:blood / Q000627:therapeutic use* / Q000652:urine; D018579:Patient Selection; D012449:Safety; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology; D055815:Young Adult
chemical_list: D004343:Drug Implants; D009292:Narcotic Antagonists; D002047:Buprenorphine