In the US, injection drug use is arguably the highest risk factor for acquiring hepatitis C virus (HCV) infection. Injection drug users in recovery in the US increasingly are seeking access to combination therapy with peginterferon alfa plus ribavirin for treatment of both hepatitis C monoinfection and HIV-HCV coinfection. With so many methadone users in this patient population, it is imperative to examine the pharmacokinetics of methadone in conjunction with that of peginterferon.

The primary aim of the current study was to quantify the pharmacokinetics of methadone and the pharmacokinetics and pharmacodynamics of peginterferon alfa-2a (40 kd) [Pegasys] in patients with chronic hepatitis C undergoing methadone maintenance therapy.

Adults with chronic hepatitis C who had been receiving a consistent methadone maintenance regimen for at least 3 months were eligible for this open-label, multicenter, nonrandomized drug interaction study.

All patients received standard dose of 180 microgram subcutaneous peginterferon alfa-2a once weekly for 4 weeks and continued their methadone regimen. Serial blood samples were collected at baseline and immediately before and for up to 168 hours after study drug administration for the purposes of quantifying methadone and peginterferon alfa-2a serum concentrations.

Results
Twenty-four patients were enrolled.

• Methadone exposure, as measured by maximum serum concentration (C_max) and area under the concentration-time curve (AUC) normalized to a 100-mg/d dose, after 4 doses of peginterferon alfa-2a increased by 10% to 15% when compared with baseline.
• The week 4/baseline ratio of the mean C_max was 1.11 (90% confidence interval [CI], 1.02-1.22), and for AUC from time 0 to 24 hours, the week 4/baseline ratio was 1.15 (90% CI, 1.08-1.23).
• The mean accumulation ratios (week 4/first dose) for C_max and AUC from time 0 to 168 hours of peginterferon alfa-2a were 2.1 and 2.3, respectively.
• The authors concluded that peginterferon alfa-2a does not appreciably alter the pharmacokinetics of methadone.

The study was sponsored by Roche, Nutley, NJ.

M Sulkowski and others. Peginterferon alfa-2a does not alter the pharmacokinetics of methadone in patients with chronic hepatitis C undergoing methadone maintenance therapy. Clinical Pharmacology and Therapeutics 77(3): 214-224. March 2005.