Lack of correlation between fluvoxamine clearance and CYP1A2 activity as measured by systemic caffeine clearance

Abstract

Objective: Evidence exists to suggest that fluvoxamine is metabolized by CYP1A2. The present study was undertaken in order to further elucidate the role of CYP1A2 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 (r _s= −0.30; P = 0.43) or between the paraxanthine/caffeine ratio in serum 6 h after caffeine intake and fluvoxamine oral clearance (r _s= −0.18; P = 0.58).

Conclusion: CYP1A2 does not appear to be of major importance in the metabolism of fluvoxamine.