FLUVOXAMINE AND FLUOXETINE DO NOT INTERACT IN THE SAME WAY WITH THE METABOLISM OF THE ENANTIOMERS OF METHADONE

Six and seven addicts treated with racemic methadone (MTD) were comedi cated with fluvoxamine (FLV) and fluoxetine (FLX), respectively. The p lasma concentrations of both (R)-(the active enantiomer) and (S)-MTD w ere increased by FLV, whereas only (R)-MTD concentrations were increas ed by the addition of FLX. This suggests that cytochrome P450IID6 (CYP 2D6), an enzyme that is strongly inhibited by FLX, preferentially meta bolizes (R)-MTD, whereas CYP1A2, which is strongly inhibited by FLV, m etabolizes both enantiomers. The choice of a selective serotonin reupt ake inhibitor in depressive addicted patients treated with MTD and the possible use of FLX or FLV to potentiate the effects of MTD in some c ases of therapeutic failure are discussed.