title: Effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of clopidogrel in rats.
abstract: 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 AUC0-t (from 9850±4060 to 27,300±6910 µg/l h; p<0.05), AUC0-∞ (from 9850±4060 to 27,600±6800 µg/l h; p<0.05) and t1/2 (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%; p<0.01) 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.
authors.affiliation: a Department of Pharmacology , College of Basic Medical Sciences, Jiamusi University , Jiamusi , P.R. China .
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: a Department of Pharmacology , College of Basic Medical Sciences, Jiamusi University , Jiamusi , P.R. China .
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: b Research Center for Drug Metabolism, College of Life Science, Jilin University , Changchun , P.R. China , and.
authors.forename: Chunxue
authors.initials: C
authors.lastname: Fang
authors.affiliation: a Department of Pharmacology , College of Basic Medical Sciences, Jiamusi University , Jiamusi , P.R. China .
authors.forename: Jincheng
authors.initials: J
authors.lastname: Zhao
authors.affiliation: c First Affiliated Hospital, Jiamusi University , Jiamusi , P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.affiliation: a Department of Pharmacology , College of Basic Medical Sciences, Jiamusi University , Jiamusi , P.R. China .
authors.forename: Qiushuang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: a Department of Pharmacology , College of Basic Medical Sciences, Jiamusi University , Jiamusi , P.R. China .
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.affiliation: a Department of Pharmacology , College of Basic Medical Sciences, Jiamusi University , Jiamusi , P.R. China .
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Liu
authors.affiliation: c First Affiliated Hospital, Jiamusi University , Jiamusi , P.R. China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Yang
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D019540:Area Under Curve; D001711:Biotransformation; D002264:Carboxylic Acids / Q000378:metabolism; D000077144:Clopidogrel; D004347:Drug Interactions; D016666:Fluvoxamine / Q000494:pharmacology*; D006207:Half-Life; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D002264:Carboxylic Acids; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D016666:Fluvoxamine; D013988:Ticlopidine
keywords: Clopidogrel; fluvoxamine; pharmacokinetics; platelet aggregation; rat