THE EFFECT OF FLUCONAZOLE ON THE CLINICAL PHARMACOKINETICS OF METHADONE

A randomized, double-blinded, placebo-controlled pharmacokinetic and s afety trial was conducted to determine the effect of fluconazole on me thadone disposition. Volunteers receiving methadone maintenance therap y were randomized to receive either 200 mg/day oral fluconazole (n = 1 3) or placebo (n = 12), After 14 days there was a 35% average increase in serum methadone area under the curve relative to baseline among pa tients receiving fluconazole (p = 0.0008). At the same time, mean seru m methadone peak and trough concentrations increased by 27% (p = 0.007 6) and 48% (p = 0.0023), respectively, and oral clearance of methadone was reduced by 24% (p = 0.0007). In contrast, the pharmacokinetics of methadone were unaltered in the placebo group, Renal clearance of met hadone was not significantly affected by fluconazole or placebo therap y. Although exposed to increased concentrations of methadone, patients treated with fluconazole did not exhibit signs or symptoms of signifi cant narcotic overdose.