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

• Published in: Journal of clinical pharmacology Vol. 56; no. 10; p. 1263
• Main Authors: Wang, Yi, Cipriano, Alessandra, Munera, Catherine, Harris, Stephen C
• Format: Journal Article
• Language: English
• Published: England 01.10.2016
• Subjects: Administration, Cutaneous; Adult; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Analgesics, Opioid - pharmacokinetics; Biotransformation; Buprenorphine - administration & dosage; Buprenorphine - adverse effects; Buprenorphine - pharmacokinetics; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Healthy Volunteers; Humans; Male; Transdermal Patch; Young Adult; transdermal delivery system; flux; buprenorphine; absolute bioavailability; dose proportionality
• ISSN: 1552-4604
• DOI: 10.1002/jcph.718

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.