title: Effects of lasofoxifene on the pharmacokinetics and pharmacodynamics of single-dose warfarin.
abstract: OBJECTIVE
  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.affiliation: Pfizer Global Research and Development, Ann Arbor, MI 48105, USA. daniele.ouellet@pfizer.com
authors.forename: Daniele
authors.initials: D
authors.lastname: Ouellet
authors.forename: Candace
authors.initials: C
authors.lastname: Bramson
authors.forename: Santos
authors.initials: S
authors.lastname: Carvajal-Gonzalez
authors.forename: Doina
authors.initials: D
authors.lastname: Roman
authors.forename: Edward
authors.initials: E
authors.lastname: Randinitis
authors.forename: Ann
authors.initials: A
authors.lastname: Remmers
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Gardner
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D018592:Cross-Over Studies; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D019934:International Normalized Ratio; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D017698:Postmenopause; D011517:Prothrombin Time; D011759:Pyrrolidines / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014859:Warfarin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000925:Anticoagulants; D011759:Pyrrolidines; D013764:Tetrahydronaphthalenes; C111332:Lasofoxifene; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases