Effects of lasofoxifene on the pharmacokinetics and pharmacodynamics of single-dose warfarin |
| |
| Authors: | Ouellet Daniele Bramson Candace Carvajal-Gonzalez Santos Roman Doina Randinitis Edward Remmers Ann Gardner Mark J |
| |
| Affiliation: | 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. |
| |
| Keywords: | drug interaction lasofoxifene pharmacodynamics pharmacokinetics warfarin |
| 本文献已被 PubMed 等数据库收录！ |
|
