A study published in the Journal of Pharmaceutical Health Care in 2016 conducted population pharmacokinetic/pharmacodynamic modeling for retrospective clinical data to investigate the effect of vitamin K2on the anticoagulant activity of warfarin in the perioperative period of catheter ablation. 579 INR values of prothrombin time from 100 patients were analyzed using the nonlinear mixed-effects modeling program NONMEM. A 1-compartment model was adapted to the pharmacokinetics of warfarin and vitamin K2, and the indirect response model was used to investigate the relationship between plasma concentration and the pharmacodynamic response of warfarin and vitamin K2.
The population parameters obtained successfully explained the observed INR values and indicated an increase in sensitivity to warfarin in patients with reduced renal function. Vitamin K2 administration of more than 20 mg caused a slight dose-dependent decrease in INR on the day of catheter ablation and a delayed INR elevation after warfarin re-initiation. A pharmacokinetic/pharmacodynamic model was successfully built to explain the retrospective INR data during catheter ablation.