Divergent effects of raloxifene HCI on the pharmacokinetics and pharmacodynamics of warfarin.

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Title:	Divergent effects of raloxifene HCI on the pharmacokinetics and pharmacodynamics of warfarin.
Author:	Miller, J W : Skerjanec, A : Knadler, M P : Ghosh, A : Allerheiligen, S R
Citation:	Pharm-Res. 2001 Jul; 18(7): 1024-8
Abstract:	PURPOSE: Evista (raloxifene HCl) is a nonsteroidal selective estrogen receptor modulator that displays estrogen agonist effects on bone and lipid metabolism but estrogen antagonist effects on the breast and endometrium. The potential for drug-drug interaction between raloxifene and warfarin was assessed in 15 healthy postmenopausal women. METHODS: Single doses of warfarin (20 mg) were administered prior to and during 2 weeks of dosing with raloxifene 120 mg/day. Each warfarin dose was followed by pharmacokinetic sampling and prothrombin time measurements. RESULTS: Raloxifene administration resulted in 7.1% and 14.1% decreases in the clearance (CLp/F) and 7.4% and 9.8% decreases in the volume of distribution (Vss/F) of R- and S-warfarin, respectively (all p less than or = 0.05). In contrast to the slightly higher plasma concentrations of R- and S-warfarin, raloxifene reduced the maximum prothrombin time (PTmax) by 10% and the area under the PT versus time curve from 0-120 h (AUCPT) by 8% (p less than 0.01). CONCLUSIONS: Raloxifene administration may result in a small increase in systemic warfarin exposure that is associated with a diminution, not augmentation, of the pharmacodynamic effect. Due to the small magnitude of this effect, concomitant administration of raloxifene and warfarin is not likely to result in clinically significant drug-drug interaction.
Review References:	None
Notes:	None
Language:	English
Publication Type:	Jou : rnal-Article
Keywords:	Anticoagulants pharmacokinetics : Anticoagulants pharmacology : Estrogen Antagonists pharmacokinetics : Estrogen Antagonists pharmacology : Raloxifene pharmacokinetics : Raloxifene pharmacology : Warfarin pharmacokinetics : Warfarin pharmacology
URL:	http://www.aaps.org/journals/pharmres.html