Rifampicin decreases exposure to sublingual buprenorphine in healthy subjects
| Autor: | Janne T. Backman, Klaus T. Olkkola, Mari Fihlman, Teijo I. Saari, Tuija Hemmilä, Jouko Laitila, Pertti J. Neuvonen, Kari Laine, Nora Hagelberg |
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| Přispěvatelé: | Medicum, Janne Backman / Principal Investigator, Department of Clinical Pharmacology, Clinicum |
| Rok vydání: | 2016 |
| Předmět: |
first‐pass metabolism
education Analgesic interaction Pharmacology rifampicin Placebo 030226 pharmacology & pharmacy 03 medical and health sciences First pass effect chemistry.chemical_compound 0302 clinical medicine Medicine General Pharmacology Toxicology and Pharmaceutics Norbuprenorphine Adverse effect ta317 sublingual and intravenous buprenorphine CYP3A4 business.industry Original Articles 3. Good health Neurology chemistry 317 Pharmacy Anesthesia Original Article Cytochrome (P450) 3A4 business 030217 neurology & neurosurgery Rifampicin Buprenorphine medicine.drug |
| Zdroj: | Pharmacology Research & Perspectives |
| ISSN: | 2052-1707 |
| Popis: | Buprenorphine is mainly metabolized by the cytochrome P450 (CYP) 3A4 enzyme. The aim of this study was to evaluate the role of first‐pass metabolism in the interaction of rifampicin and analgesic doses of buprenorphine. A four‐session paired cross‐over study design was used. Twelve subjects ingested either 600 mg oral rifampicin or placebo once daily in a randomized order for 7 days. In the first part of the study, subjects were given 0.6‐mg (placebo phase) or 0.8‐mg (rifampicin phase) buprenorphine sublingually on day 7. In the second part of the study, subjects received 0.4‐mg buprenorphine intravenously. Plasma concentrations of buprenorphine and urine concentrations of buprenorphine and its primary metabolite norbuprenorphine were measured over 18 h. Adverse effects were recorded. Rifampicin decreased the mean area under the dose‐corrected plasma concentration–time curve (AUC 0–18) of sublingual buprenorphine by 25% (geometric mean ratio (GMR): 0.75; 90% confidence interval (CI) of GMR: 0.60, 0.93) and tended to decrease the bioavailability of sublingual buprenorphine, from 22% to 16% (P = 0.31). Plasma concentrations of intravenously administered buprenorphine were not influenced by rifampicin. The amount of norbuprenorphine excreted in the urine was decreased by 65% (P |
| Databáze: | OpenAIRE |
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