C. Iribarne et al., IN-VITRO INTERACTIONS BETWEEN FLUOXETINE OR FLUVOXAMINE AND METHADONEOR BUPRENORPHINE, Fundamental and clinical pharmacology, 12(2), 1998, pp. 194-199
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.