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Dose‐Dependent Flux of Buprenorphine Following Transdermal Administration in Healthy Subjects
Author(s) -
Wang Yi,
Cipriano Alessandra,
Munera Catherine,
Harris Stephen C.
Publication year - 2016
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.718
Subject(s) - buprenorphine , transdermal , medicine , anesthesia , administration (probate law) , pharmacology , emergency medicine , opioid , receptor , political science , law
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.