Figure 1.
Flow diagram of the randomized trial of the control and genotype groups.
The patient numbers participated during the entire date range of the study were shown in parentheses and samples analyzed in this study were collected from 2010 to 2012.
Table 1.
Patient demographics.
Figure 2.
The population pharmacokinetic-pharmacodynamic (PK-PD) models of warfarin.
Three models were employed to describe the time courses of the plasma concentration of S-warfarin, Cp(S) by the 1-compartment model (Eq.1) and normal prothrombin (NPT) by the indirect model (Eq.2) and the INR by the nonlinear model (Eq.3). Population parameters of CL(S) in PK, IC50 and Kout in PD-1 and λ in PD-2 were estimated.
Figure 3.
Diagnostic plots employed to evaluate population analyses.
Relationships between population predictions of Cp(S) (A), NPT (B) and INR (C) and the observed values (left panel), those between individual predictions of Cp(S) (A), NPT (B) and INR (C) and the corresponding observed values (middle panel), and those between population predictions of Cp(S) (A), NPT (B) and INR (C) and weighted residuals (right panel).
Table 2.
Summary of population PK-PD parameters for Cp(S), NPT and INR.
Figure 4.
Impacts of predictors extracted from PK-PD analyses.
Influences of CYP2C9*3 mutation and body surface area (BSA) on CL(S) in the time courses of Cp(S) (A), VKORC1*2 and CYP4F2*3 on IC50 in the time courses of NPT (B and C, respectively) and NPT0 on λ in the relationship between NPT and INR (D) were predicted in typical Chinese patients with a BSA of 1.77 m2 (165 cm and 70 kg) after administration of racemic warfarin at 3.0 mg/d.
Figure 5.
Comparisons of PK-PD parameters between the INR≥4 and <4 groups.
Oral clearance of S-warfarin, CL(S), IC50 and the exponent λ were compared between the two groups of patients with an INR of ≥4 and <4 during warfarin induction treatment. Data are shown as box-and-whisker plots. The horizontal line indicates the median and the box covers the 25–75th percentiles. Closed circles (•) are outliers. **P<0.01 between the two groups.
Table 3.
Logistic regression analysis of predictors associated with INR≥4.