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

Abstract

Background FA 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]. Methods WAR 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). Results Among 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