EFFECT OF CIGARETTE SMOLTING ON FLUVOXAMINE PHARMACOKINETICS IN HUMANS

Objectives: Although fluvoxamine inhibits the biotransformation of dru gs known to be metabolized by CYP1A2, there are no data available with regard to the importance of CYP1A2 for the metabolism of fluvoxamine itself. Because smoking induces the metabolism of drugs catalyzed by C YP1A2, this study investigated the pharmacokinetics of fluvoxamine in smelters and nonsmokers. Methods: The serum concentration of fluvoxami ne was determined by high-performance liquid chromatography for 48 hou rs after oral administration of a single dose of 50 mg fluvoxamine to 12 smokers (greater than or equal to 10 cigarettes per day) and 12 non smokers. Results: The smokers had significantly lower areas under the serum concentration-time curve and significantly lower maximal serum c oncentrations than the nonsmokers (mean +/- SD, 771 +/- 346 versus 111 0 +/- 511 nmol . hr . L(-1) [p = 0.012] and 39.1 +/- 17.3 versus 57.7 +/- 21.5 nmol . L(-1) [p = 0.012], respectively). The terminal elimina tion half-life did not differ significantly between smokers and nonsmo kers (10.1 +/- 1.9 and 10.7 +/- 2.3 hours, respectively), The oral cle arance was high among both smokers (4.1 +/- 1.9 L . min(-1)) and nonsm okers (3.3 +/- 2.7 L . min(-1); difference not significant). Conclusio n: Smokers had lower serum concentrations of fluvoxamine than nonsmoke rs after a single oral dose of fluvoxamine. This finding is consistent with a possible role of CYP1A2 in fluvoxamine metabolism.