EFFECT OF CIGARETTE SMOLTING ON FLUVOXAMINE PHARMACOKINETICS IN HUMANS

Objectives: Although fluvoxamine inhibits the biotransformation of drugs 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 CYP1A2, this study investigated the pharmacokinetics of fluvoxamine in smelters and nonsmokers. Methods: The serum concentration of fluvoxamine was determined by high-performance liquid chromatography for 48 hours 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 nonsmokers. Results: The smokers had significantly lower areas under the serum concentration-time curve and significantly lower maximal serum concentrations than the nonsmokers (mean +/- SD, 771 +/- 346 versus 1110 +/- 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 elimination half-life did not differ significantly between smokers and nonsmokers (10.1 +/- 1.9 and 10.7 +/- 2.3 hours, respectively), The oral clearance was high among both smokers (4.1 +/- 1.9 L . min(-1)) and nonsmokers (3.3 +/- 2.7 L . min(-1); difference not significant). Conclusion: Smokers had lower serum concentrations of fluvoxamine than nonsmokers after a single oral dose of fluvoxamine. This finding is consistent with a possible role of CYP1A2 in fluvoxamine metabolism.