Pharmacokinetic interaction between HCV protease inhibitor boceprevir and methadone or buprenorphine in subjects on stable maintenance therapy
| Autor: | Edward O'Mara, Joan R. Butterton, Wen H. Lin, John A. Wagner, Hwa-Ping Feng, Lynn Webster, R. Douglas Bruce, Ellen G. J. Hulskotte, Feng Xuan |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Adolescent Proline Hepatitis C virus (+)-Naloxone Pharmacology medicine.disease_cause Maintenance Chemotherapy Young Adult chemistry.chemical_compound Pharmacokinetics Maintenance therapy Boceprevir Opiate Substitution Treatment Humans Medicine Drug Interactions Protease Inhibitors Pharmacology (medical) Aged business.industry General Medicine Middle Aged Drug interaction Buprenorphine chemistry Female Buprenorphine Naloxone Drug Combination business Methadone medicine.drug |
| Zdroj: | European Journal of Clinical Pharmacology. 71:303-311 |
| ISSN: | 1432-1041 0031-6970 |
| Popis: | Intravenous opioid use is a common route of hepatitis C virus (HCV) infection; consequently, the prevalence of HCV is high among patients on methadone or buprenorphine/naloxone. The authors evaluated the pharmacokinetic interaction of boceprevir with methadone or buprenorphine/naloxone in patients on stable maintenance therapy. This was a two-center, open-label, fixed-sequence study in 21 adult volunteers on stable maintenance therapy. Oral methadone (20–150 mg once daily) or sublingual buprenorphine/naloxone (8/2–24/6 mg once daily) was administered alone or in combination with boceprevir (800 mg every 8 h) on days 2–7. Pharmacokinetic sampling occurred before and up to 24 h after the dose on days 1 and 7. Coadministration of boceprevir reduced the area under the concentration-time curve during a dosing interval τ (AUC τ ) and maximum observed plasma (or serum) concentration (C max) of R-methadone (geometric mean ratios (GMRs) [90 % confidence intervals (CIs)], 0.85 [0.74, 0.96] and 0.90 [0.71, 1.13]) and S-methadone (GMRs [90 % CIs], 0.78 [0.66, 0.93] and 0.83 [0.64, 1.09]). Boceprevir increased the AUC τ and C max of buprenorphine (GMRs [90 % CIs], 1.19 [0.91, 1.58] and 1.18 [0.93, 1.50]) and naloxone (GMRs [90 % CIs], 1.33 [0.90, 1.93] and 1.09 [0.79, 1.51]). Boceprevir exposure upon methadone or buprenorphine/naloxone coadministration was not clinically different from historical controls and there was no evidence of opioid withdrawal or excess. There was no clinically meaningful impact of boceprevir on methadone or buprenorphine pharmacokinetics, suggesting that methadone/buprenorphine dose adjustments are not required upon coadministration with boceprevir. Individual patients may differ in their clinical experience and clinicians should maintain vigilance when coadministering these medications. |
| Databáze: | OpenAIRE |
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