Pharmacokinetics, Pharmacodynamics and Antiviral Response in Patients with Chronic Hepatitis C Infection on Methadone Maintenance Therapy Receiving Pegasys (peginterferon alfa-2a)
The primary objective of the present study was to evaluate the potential for pharmacokinetic (PK), pharmacodynamic (PD) and clinical drug interactions with the concomitant use of 180 microgram PEG-IFN and methadone in CHC patients on MMT.
The PK and PD of PEG-IFN were evaluated after single and multiple weekly 180 microgram doses in 24 CHC patients on MMT. PEG-IFN's effect on methadone pharmacokinetics was assessed by the comparison of methadone's PK before and after multiple doses of PEG-IFN.
The PD effects of PEG-IFN were assessed by measuring 2',5'-oligoadenylate synthetase (2',5'-OAS) serum activity and HCV kinetics. Non-compartmental PK and PD analyses, including descriptive statistics and an ANOVA, were completed.
The majority of patients enrolled were male (63%), Caucasian (63%), 50 to 124 kg, and 34 to 57 years old. Patients received stable daily methadone doses of 30 to 150 mg. PEG-IFN PK at week 1 and week 4 was similar to PEG-IFN PK determined from historic data in CHC patients not receiving MMT.
Methadone PK was similar at baseline and after 4 weeks of PEG-IFN treatment. PEG-IFN-induced 2',5'-OAS activity after a single dose was similar to that seen in healthy subjects.
Twelve of 20 (60%) patients demonstrated a virological response (undetectable [<600 IU/mL] or a 2-log10 drop in HCV RNA serum concentrations) by treatment week 4.
The most frequently reported adverse events included headache, myalgia, pyrexia, fatigue and anorexia; most were mild or moderate in intensity. No signs of opioid withdrawal were observed. No patient modified methadone or PEG-IFN doses during the study. One subject withdrew prematurely due to poor venous access.
- PEG-IFN monotherapy is well tolerated by CHC patients receiving MMT;
- PEG-IFN and methadone do not significantly alter the PK of each respective therapy;
- Biologic response as assessed by 2',5'-OAS activity was similar to that in healthy subjects;
- HCV RNA decline was similar to that seen in CHC patients not receiving MMT;
- These data suggest that MMT does not impair the antiviral activity of PEG-IFN.
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