title: Dose-Dependent Flux of Buprenorphine Following Transdermal Administration in Healthy Subjects.
abstract: Buprenorphine transdermal delivery system (BTDS) applied once every 7 days is indicated for the management of pain that is severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. The 7-day flux of buprenorphine from BTDS to systemic circulation was investigated in a phase 1, 2-period crossover study with 3 randomized groups of healthy subjects receiving BTDS containing buprenorphine 5, 10, or 20 mg for 7 days preceded or followed by intravenous buprenorphine infusion (25 μg/h for 24 hours). Residual and absolute bioavailability methods were used to estimate 7-day flux of buprenorphine. Following BTDS administration, mean area under the curve of buprenorphine increased proportionally (12.6, 24.3, and 51.1 ng/[mL · h]), maximum mean plasma concentration rose with increasing dose (176, 191, and 471 pg/mL), and absolute bioavailability was 14% to 16%. Mean residual amount of buprenorphine in the BTDS after 7-day application was 4.50, 8.57, and 17.1 mg. Flux of buprenorphine was approximately 5, 10, and 20 μg/h for BTDS containing 5, 10, and 20 mg buprenorphine, respectively. BTDS was safe and well tolerated following a single 7-day application in healthy subjects. The results of this study demonstrated dose-dependent flux of buprenorphine delivered via transdermal system.
authors: One Stamford Forum, Purdue Pharma, Stamford, CT, USA.
authors: Yi
authors: Y
authors: Wang
authors: One Stamford Forum, Purdue Pharma, Stamford, CT, USA.
authors: Alessandra
authors: A
authors: Cipriano
authors: One Stamford Forum, Purdue Pharma, Stamford, CT, USA.
authors: Catherine
authors: C
authors: Munera
authors: One Stamford Forum, Purdue Pharma, Stamford, CT, USA. Stephen.Harris@pharma.com.
authors: Stephen C
authors: SC
authors: Harris
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001711:Biotransformation; D002047:Buprenorphine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D057968:Transdermal Patch; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine
keywords: absolute bioavailability; buprenorphine; dose proportionality; flux; transdermal delivery system