The effect of folic acid (FA) supplumentation on warfarin (WAR) dose requirement and the formation clearance of (S)-7' OH-warfarin (original) (raw)

Clinical Pharmacology & Therapeutics, 2005

Abstract

ABSTRACT BackgroundFA supplementation in patients with FA deficiency is associated with increased clearance of phenytoin towards its CYP2C9-mediated metabolite, p-HPPH. The aim of this study was to determine the effect of FA concentration and supplementation on the dose requirement of the CYP2C9 substrate WAR, and the formation clearance of (S)-7' OH-warfarin[CLf7OHW].MethodsWAR dose was recorded, and CLf7OHW and FA concentrations were measured in 98 patients at stable WAR anticoagulation. In 22 patients with FA deficiency CLf7OHW was re-evaluated following FA treatment (5mg/day).ResultsAmong patient with FA deficiency FA concentration was 3.99±1.86 ng/ml prior to and 21.65±5.84 ng/ml following FA treatment (p<0.0001). CLf7OHW increased following FA treatment from 1.06±0.86 to 2.11±2.48, ml/min, (p= 0.017), however there was no difference in WAR dose (5.93± 2.38 vs. 6.06±2.51, mg/day, p=0.30). There was no significant correlation between FA concentration and WAR dose or CLf7OHW in the entire cohort (n=98).Conclusions In patients with FA deficiency, FA supplementation was associated with increased CLf7OHW. Further study is warranted to determine the clinical significance of the interaction between WAR and FA.Clinical Pharmacology & Therapeutics (2005) 77, P41-P41; doi: 10.1016/j.clpt.2004.12.051

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