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.

Source: Effect of vitamin K2 on the anticoagulant activity of warfarin during the perioperative period of catheter ablation: Population analysis of retrospective clinical data