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Br J Clin Pharmacol. 2006 Jun;61(6):741-5.

Effects of lasofoxifene on the pharmacokinetics and pharmacodynamics of single-dose warfarin.

Author information

1
Pfizer Global Research and Development, Ann Arbor, MI 48105, USA. daniele.ouellet@pfizer.com

Abstract

AIM:

To investigate the effect of steady-state lasofoxifene on the pharmacokinetics and pharmacodynamics of warfarin.

METHODS:

Twelve healthy postmenopausal women received warfarin (single 20-mg dose) alone and during lasofoxifene. R- and S-warfarin concentrations, prothrombin time (PT) and international normalized ratio (INR) were determined with each treatment.

RESULTS:

Lasofoxifene had no clinically meaningful effect on R- or S-warfarin pharmacokinetics. The S-warfarin area under the plasma concentration-time curve (AUC) was 23% and 67% larger in subjects with *1/*2 and *1/*3 heterozygous mutations, relative to *1/*1, respectively. The mean PT AUC and Cmax ratio (90% confidence interval) was 91.9 (89.6, 94.2) and 84.2 (80.6, 87.8), respectively. INR results were similar.

CONCLUSIONS:

Lasofoxifene has no clinically meaningful effect on the pharmacokinetics of warfarin. Although the decrease in PT/INR may not be clinically meaningful, more frequent INR monitoring may be considered during lasofoxifene introduction and discontinuation, consistent with warfarin's label.

PMID:
16722839
PMCID:
PMC1885106
DOI:
10.1111/j.1365-2125.2006.02589.x
[Indexed for MEDLINE]
Free PMC Article
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