AIM: To investigate the effect of steady-state lasofoxifene on the pharmacokinetics and pharmacodynamics of warfarin. METHODS:Twelve healthy postmenopausal women receivedwarfarin (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.
RCT Entities:
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.
Authors: R Loebstein; H Yonath; D Peleg; S Almog; M Rotenberg; A Lubetsky; J Roitelman; D Harats; H Halkin; D Ezra Journal: Clin Pharmacol Ther Date: 2001-08 Impact factor: 6.875
Authors: Steven Lane; Sameh Al-Zubiedi; Ellen Hatch; Ivan Matthews; Andrea L Jorgensen; Panos Deloukas; Ann K Daly; B Kevin Park; Leon Aarons; Kayode Ogungbenro; Farhad Kamali; Dyfrig Hughes; Munir Pirmohamed Journal: Br J Clin Pharmacol Date: 2012-01 Impact factor: 4.335