Lack of correlation between fluvoxamine clearance and CYP1A2 activity as measured by systemic caffeine clearance.
OBJECTIVE
Evidence exists to suggest that fluvoxamine is metabolized by CYP1A2. The present study was undertaken in order to further elucidate the role of CYPIA2 in fluvoxamine disposition.


METHODS
Twelve healthy non-smoking male volunteers participated in this cross-over study. Six subjects received first fluvoxamine 50 mg as a single oral dose and, some weeks later, caffeine 200 mg as a single oral dose. The other six subjects received the drugs in reverse order. Serum concentrations of fluvoxamine, caffeine and paraxanthine were measured and standard pharmacokinetic parameters were calculated.


RESULTS
There were no significant correlations between caffeine clearance and fluvoxamine oral clearance (rs = -0.30; P = 0.43) or between the paraxanthine/caffeine ratio in serum 6 h after caffeine intake and fluvoxamine oral clearance (rs = -0.18; P = 0.58).


CONCLUSIONS
CYP1A2 does not appear to be of major importance in the metabolism of fluvoxamine.
Spigset
O
O
Norrland University Hospital, Umeå, Sweden. olav.spigset@relis.rit.no
Hägg
S
S
Söderström
E
E
Dahlqvist
R
R
D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D004347:Drug Interactions; D016666:Fluvoxamine / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics*
D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2; D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors; D013806:Theophylline; C021183:1,7-dimethylxanthine