Evaluation of pharmacokinetics of warfarin from validated pharmacokinetic-pharmacodynamic model.

Background: Pharmacokinetics of warfarin has not been described in our population. We derived the pharmacokinetic parameters from a validated pharmacokinetic-pharmacodynamic model.

Methods: Patients receiving warfarin for at least 6 months were recruited and their demographic characteristics, prothrombin time international normalized ratio (PT-INR), warfarin doses and concomitant drugs were collected. Using a validated pharmacokinetic-pharmacodynamic model, we predicted maximum plasma concentration ( ), total clearance ( ), volume of distribution ( ) and elimination rate (). Warfarin sensitive index (WSI) and warfarin composite measures (WCM) were estimated from the dose and INR values. Liver weight was predicted using validated formula.

Results: Two-hundred and twenty patients were recruited. The following were the predicted pharmacokinetic parameters: (mg/L) was 5.8 (0.4); (L/day) was 1 (0.1); CL (L/day) was 2.1 (0.2); and (L) was 7.6 (0.2). Patients with and elimination rate outside the mean+1.96 SD had significantly lower WSI and higher WCM. Significant correlations were observed between with CL, , and of warfarin. Significant correlations were also observed between CL and of warfarin with liver weight of the study participants.

Conclusion: We predicted pharmacokinetic parameters of warfarin from the validated pharmacokinetic-pharmacodynamic model in our population. More studies are needed exploring the relationship between various pharmacodynamic indices of warfarin and pharmacokinetic parameters of warfarin.