O. Spigset et al., EFFECT OF CIGARETTE SMOLTING ON FLUVOXAMINE PHARMACOKINETICS IN HUMANS, Clinical pharmacology and therapeutics, 58(4), 1995, pp. 399-403
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.