title: Effect of single-dose rifampin on the pharmacokinetics of warfarin in healthy volunteers.
abstract: Based on in vitro rat and human hepatocyte uptake studies showing inhibition of warfarin uptake in the presence of the nonspecific organic anion-transporting polypeptide (OATP) inhibitor rifampin, a clinical study was conducted in 10 healthy volunteers to examine the in vivo relevance of OATP hepatic uptake on the pharmacokinetics of warfarin. In a randomized, single-dose, two-period, crossover design, subjects received a 7.5-mg dose of warfarin, either alone or immediately following a 600-mg intravenous dose of rifampin. Rifampin did not significantly alter the R- or S-warfarin area under the concentration-time curves (AUCs) from 0 to 12 h (period of hepatic OATP inhibition by rifampin) or the maximum plasma concentration (C(max)) value. AUC(0-∞) was decreased on days rifampin was administered, for both R-warfarin (25% reduction; P < 0.001) and S-warfarin (15% reduction; P < 0.05). No differences were seen in the area under the international normalized ratio (INR)-time curve. Our study suggests that hepatic uptake via OATPs may not be clinically important in the pharmacokinetics of warfarin.
authors: Division of Clinical Pharmacology, University of California, San Francisco, San Francisco, California, USA.
authors: A
authors: A
authors: Frymoyer
authors: S
authors: S
authors: Shugarts
authors: M
authors: M
authors: Browne
authors: A H B
authors: AH
authors: Wu
authors: L
authors: L
authors: Frassetto
authors: L Z
authors: LZ
authors: Benet
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008657:Metabolic Clearance Rate; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000494:pharmacology*; D014859:Warfarin / Q000493:pharmacokinetics*
chemical_list: D000925:Anticoagulants; D004791:Enzyme Inhibitors; D027361:Organic Anion Transporters; D014859:Warfarin; D012293:Rifampin