IN-VITRO INTERACTIONS BETWEEN FLUOXETINE OR FLUVOXAMINE AND METHADONEOR BUPRENORPHINE

Methadone and buprenorphine, widely used in the treatment of opioid ab use, are metabolized by cytochrome P450 3A4, while fluoxetine and fluv oxamine, both selective serotonin reuptake inhibitors, are known to be P450 2D6 and 3A4 inhibitors in vitro. This study deals with the in vi tro interactions between methadone or buprenorphine and fluoxetine or fluvoxamine. Fluoxetine inhibited methadone N-demethylation (Ki = 55 m u M), but conversely did not inhibit buprenorphine dealkylation. Norfl uoxetine inhibited the metabolism of both methadone and buprenorphine metabolisms (Ki 13 and 100 mu M, respectively). Fluvoxamine inhibited methadone N-demethylation with a Ki of 7 mu M and buprenorphine dealky lation, uncompetitively, with a Ki of 260 mu M. Finally, these results suggest that care should be taken when selective serotonin reuptake i nhibitors are administered in the treatment of drug craving. This is p articularly true in the case of fluvoxamine which is more potent than fluoxetine in inhibiting methadone and buprenorphine metabolism. (C) 1 998 Elsevier, Paris.