Weekly administration of PEG-IFN alfa-2b to subjects with chronic hepatitis C increased CYP2C8/9 and CYP2D6 activity in some individuals.

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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.

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Aims To assess the dose selection using population pharmacokinetics of Pegylated Intron‐α2b (PEG‐Intron) in patients with chronic myelogenous leukaemia (CML). Methods PEG‐Intron 3–6 µg kg−1 was administered subcutaneously once a week and blood samples were collected up to 48 weeks of treatment. A total of 624 samples collected from 137 patients were included in the analysis. Nonlinear mixed‐effects modelling was used to analyse the sparsely sampled concentration data from a clinical efficacy trial. Covariates in the analysis included weight, sex, age, race, serum creatinine and estimated creatinine clearance (CLcr). Results The apparent clearance of PEG‐Intron decreased after repeated dosing. The clearance at treatment week 4 was 42.3 l day−1 (patients with CLcr 120 ml min−1) with interpatient variability 30%. At treatment week 48, the clearance value was reduced to 69% of its week 4 value. CLcr, a composite variable calculated from body weight, sex, age and serum creatinine, had a small but statistically significant influence on the clearance of PEG‐Intron. The clearance of PEG‐Intron in patients with CML was 40% higher than that of hepatitis C virus‐infected patients. Conclusion The dose of PEG‐Intron 6.0 µg kg−1 week−1 appeared appropriate in the treatment of patients with CML.