Effect of Interferona2b on Methadone Pharmacokinetics

Methadone, a racemic mixture, is primarily metabolized by CYP3A4, secondarily by CYP2D6, and to a lesser extent by CYP1A2 and CYP2B6 (18). Gupta et al. (24) evaluated the effects of multiple doses of peg-IFN-a2b (PEGASYS) on the steady-state pharmacokinetics of methadone in patients with hepatitis C. Twenty adults with hepatitis C virus infection received peg-IFN-a2b (1.5 mg/kg/wk) SC for four weeks and maintained their normal methadone regimen (approximately 40 mg/day). There was approximately 15% increase in the exposure of individual isomers as well as total methadone after four weekly doses of peg-IFN-a2b, as compared with the exposure observed before peg-IFN-a2b administration. According to the authors, this increase in methadone exposure may not be of any clinical significance, although this study further supports the concept that peg-IFN-a2b can modulate metabolic enzyme functions associated with drug clearance.

Berk et al. (25) studied the effect of peg-IFN-a2b (1.5 mg/kg given SC, 2 doses given one week apart) on steady-state pharmacokinetics of methadone (40-200 mg/day given orally) in nine patients with hepatitis C virus and HIV. Overall, a 24% and 17% increase in mean methadone Cmax and AUC(0-24) was observed after two weeks of peg-IFN-a2b administration. No dosage adjustment of methadone was suggested by the authors when it was given with peg-IFN-a2b in patients with hepatitis C virus and HIV.

0 0

Post a comment