The effect of fluconazole on the clinical pharmacokinetics of methadone.
A randomized, double-blinded, placebo-controlled pharmacokinetic and safety trial was conducted to determine the effect of fluconazole on methadone disposition. Volunteers receiving methadone maintenance therapy were randomized to receive either 200 mg/day oral fluconazole (n = 13) or placebo (n = 12). After 14 days there was a 35% average increase in serum methadone area under the curve relative to baseline among patients receiving fluconazole (p = 0.0008). At the same time, mean serum methadone peak and trough concentrations increased by 27% (p = 0.0076) 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 methadone was not significantly affected by fluconazole or placebo therapy. Although exposed to increased concentrations of methadone, patients treated with fluconazole did not exhibit signs or symptoms of significant narcotic overdose.
Cobb
M N
MN
Addiction Research and Treatment Corporation, Division of Medical Services, Evaluation and Research, Brooklyn, NY 11201, USA.
Desai
J
J
Brown
L S
LS
Zannikos
P N
PN
Rainey
P M
PM
D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009294:Narcotics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors
D000935:Antifungal Agents; D009294:Narcotics; D015725:Fluconazole; D008691:Methadone