Effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of clopidogrel in rats

1. Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is often coprescribed with clopidogrel for the treatment of ischemic vascular diseases. The aim of this study was to explore the effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of clopidogrel. 2. Twelve male rats were employed to investigate the effect of fluvoxamine on the pharmacokinetics of clopidogrel in vivo. Clopidogrel carboxylic acid was used for the pharmacokinetic study of clopidogrel. 3. After pretreatment with high dose of fluvoxamine (27 mg/kg), there were significant increases in the AUC(0) (-) (t) (from 9850 +/- 4060 to 27 300 +/- 6910 mu g/l h; p<0.05), AUC(0 - infinity) (from 9850 +/- 4060 to 27 600 +/- 6800 mu g/l h; p<0.05) and t(1/2) (from 2.07 +/- 0.0942 to 7.49 +/- 1.22 h; p<0.05) of clopidogrel carboxylic acid. The pharmacokinetic data for clopidogrel carboxylic acid showed significant decreases in VLz/F (from 0.765 +/- 0.299 to 0.256 +/- 0.0594 l/kg; p<0.05) after pretreatment with high dose of fluvoxamine. Pharmacodynamic studies that measure platelet aggregation percentage (from 21.63 +/- 6.05% to 45.98 +/- 5.11%; p50.01) show that high doses of fluvoxamine significantly inhibit the effect of clopidogrel. 4. In conclusion, the pharmacokinetics and pharmacodynamics of clopidogrel were significantly affected by high doses of fluvoxamine. This study indicated that potential drug-drug interaction between fluvoxamine and clopidogrel should be taken into consideration in clinical use.