The effect of multiple doses of peginterferon alfa-2b on the steady-state pharmacokinetics of methadone in patients with chronic hepatitis C undergoing methadone maintenance therapy

Abstract

This multicenter, open-label study evaluated the effects of multiple doses of peginterferon alfa-2b on the steady-state pharmacokinetics of methadone in 20 adults with hepatitis C virus infection who were enrolled in a methadone maintenance program. All subjects received peginterferon alfa-2b 1.5 μg/kg/wk for 4 weeks and maintained their normal methadone regimen. Serial blood samples were collected immediately before the first and after the fourth peginterferon alfa-2b dose (day 23). At day 23, exposure to the active methadone R-enantiomer increased by approximately 15% following administration of peginterferon alfa-2b, with 90% confidence intervals just outside the bioequivalence criteria (range, 80%-125%). Similar increases in exposure (Cmax, AUC 0-24, and AUClast) were observed with S-methadone and total methadone. Peginterferon alfa-2b was well tolerated. Peginterferon alfa-2b is associated with minor increases in exposure to methadone in individuals with hepatitis C virus infection; however, these increases are unlikely to be clinically meaningful and are not associated with any safety concerns. ©2007 the American College of Clinical Pharmacology.