Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir

Abacavir and amprenavir, a nucleoside reverse transcription inhibitor and a protease inhibitor, respectively, are new drugs used for the treatment of HIV. Methadone blood concentrations were measured in five addict patients r eceiving methadone maintenance therapy before and after introduction of aba cavir plus amprenavir. The administration of these two drugs for a median p eriod of 14 days resulted in a significant reduction (P=0.043) of methadone concentration, with a median decrease to 35% of the original concentration (range 28-87%). Two patients reported on several occasions nausea in the m orning before the intake of the daily methadone dose, which is compatible w ith withdrawal reaction to opioids. Because amprenavir is a cytochrome P450 3A4 substrate and is involved in the metabolism of methadone, reduction of methadone concentrations could be explained by an induction of cytochrome P 4503A4.