title: Effect of clopidogrel on the steady-state pharmacokinetics of fluvastatin.
abstract: This study assessed the effects of clopidogrel, a CYP 2C9 inhibitor, on fluvastatin pharmacokinetics in healthy volunteers. The effects of combined clopidogrel-fluvastatin treatment on platelet function were also determined. Subjects received 80 mg fluvastatin (extended-release formulation) alone on days 1 through 9, 80 mg fluvastatin and 300 mg clopidogrel (loading dose) on day 10, and 80 mg fluvastatin and 75 mg clopidogrel (maintenance dose) on days 11 through 19. Compared to treatment with fluvastatin alone, fluvastatin AUC was similar and C(max) increased marginally (15.7%) with concomitant treatment with clopidogrel. Platelet aggregation was inhibited by clopidogrel by 33% two hours after the loading dose and by 47% at steady state, similar to that reported for clopidogrel alone treatment. The authors conclude that coadministration of fluvastatin and clopidogrel has no clinically relevant effect on fluvastatin pharmacokinetics or on platelet inhibition by clopidogrel.
authors: Novartis Pharmaceuticals, One Health Plaza, East Hanover, NJ 07936, USA. surya.ayalasomayajula@novartis.com
authors: Surya P
authors: SP
authors: Ayalasomayajula
authors: Sujata
authors: S
authors: Vaidyanathan
authors: Charisse
authors: C
authors: Kemp
authors: Pratapa
authors: P
authors: Prasad
authors: Alfred
authors: A
authors: Balch
authors: William P
authors: WP
authors: Dole
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D000077144:Clopidogrel; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007211:Indoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D010975:Platelet Aggregation Inhibitors; D000077340:Fluvastatin; D000077144:Clopidogrel; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D013988:Ticlopidine