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Lack of effect of CYP3A4 inhibitor ketoconazole on transdermally administered buprenorphine

Objective To evaluate the effect of ketoconazole on the pharmacokinetics of buprenorphine and its metabolites following application of a 10‐mg buprenorphine transdermal system (BTDS). Methods This was a randomized, double‐blind, 2‐treatment, 2‐period crossover study with 20 healthy male and female s...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2005-02, Vol.77 (2), p.P78-P78
Main Authors: Noveck, R., Harris, S., El‐Tahtawy, A., Kim, R., Reidenberg, B., Chung, J., Chen, D.
Format: Article
Language:English
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Summary:Objective To evaluate the effect of ketoconazole on the pharmacokinetics of buprenorphine and its metabolites following application of a 10‐mg buprenorphine transdermal system (BTDS). Methods This was a randomized, double‐blind, 2‐treatment, 2‐period crossover study with 20 healthy male and female subjects. Treatments: BTDS for 7 days with ketoconazole (200 mg po, bid) or placebo in crossover fashion. Results The 90% confidence intervals for the estimated ratios of population geometric means for buprenorphine AUCt and Cmax were within 80% to 125%. Plasma concentrations of norbuprenorphine, and norbuprenorphine glucuronide, were detected in both treatments and were not lower in the BTDS+ ketoconazole treatment. Plasma concentrations of buprenorphine‐3‐glucuronide were measurable in 5 out of 18 BTDS+ ketoconazole subjects. No apparent safety concerns were identified. Eight subjects had hyperpigmentation at the application site (4 events were resolved and 4 were continuing). Conclusions Plasma concentrations of buprenorphine from BTDS did not differ during co‐medication with ketoconazole 200 mg bid vs. placebo. BTDS dose adjustment is not needed for subjects taking concomitant CYP3A4 inhibitors. Clinical Pharmacology & Therapeutics (2005) 77, P78–P78; doi: 10.1016/j.clpt.2004.12.188
ISSN:0009-9236
1532-6535
DOI:10.1016/j.clpt.2004.12.188