The influence of (R)- and (S)-warfarin, vitamin K and vitamin K epoxide upon warfarin anticoagulation.
The contribution of (R)- and (S)-warfarin enantiomers, vitamin K and vitamin K epoxide and patient factors to inter-individual variability in daily warfarin requirements were examined in a group of 73 patients. Simple correlation analysis showed a significant positive relationship between INR values and plasma (S)-warfarin concentrations (r = 0.25; p = 0.038). Multivariate analysis for relationships with INR demonstrated a highly significant positive relationship between INR and (S)-warfarin (p = 0.004) and plasma vitamin K epoxide concentrations (p = 0.028), and a significant negative relationship between INR and plasma vitamin K concentrations (p = 0.034). Twenty five percent of variation in INR could be explained by these variables (adjusted R2 = 0.25). Correlation analysis of data showed that warfarin dosage was significantly and negatively correlated with patient age (r = -0.42; p <0.0001). Patient age accounted for 25% of variation in warfarin dosage requirements (R2 = 0.25). The combined effects of age and vitamin K appear to account for much of the inter-individual variability in warfarin dosage requirements.
Wolfson Unit of Clinical Pharmacology, University of Newcastle, Newcastle upon Tyne, UK. Farhad.Kamali@ncl.ac.uk
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F
Kamali
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Edwards
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TJ
Butler
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Wynne
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D014644:Genetic Variation; D006801:Humans; D019934:International Normalized Ratio; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D013237:Stereoisomerism; D014812:Vitamin K / Q000097:blood*; D010837:Vitamin K 1 / Q000031:analogs & derivatives* / Q000097:blood; D014859:Warfarin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000925:Anticoagulants; D001779:Blood Coagulation Factors; D014812:Vitamin K; C016186:vitamin K1 oxide; D014859:Warfarin; D010837:Vitamin K 1