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.
This multicenter, open-label study evaluated the effects of multiple doses of peginterferon alfa-2b on the steadystate 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 mug/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 (C(max), AUC(0-24), and AUC(last)) 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.
Gupta
Samir K
SK
MBA, Schering-Plough Research Institute K15-22745, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA samir.gupta@spcorp.com
Sellers
Edward
E
Somoza
Eugene
E
Angles
Luis
L
Kolz
Karen
K
Cutler
David L
DL
D000328:Adult; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics*; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy; D006556:Heroin Dependence / Q000097:blood / Q000188:drug therapy; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008691:Methadone / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D009294:Narcotics / Q000097:blood / Q000493:pharmacokinetics; D011092:Polyethylene Glycols; D011994:Recombinant Proteins
D000701:Analgesics, Opioid; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009294:Narcotics; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; D008691:Methadone