Population pharmacokinetic/pharmacodynamic modeling of warfarin by nonlinear mixed effects model / 药学学报
Acta Pharmaceutica Sinica
;
(12): 1280-1284, 2015.
Article
in Chinese
| WPRIM
| ID: wpr-320089
ABSTRACT
The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows CL = θCL · (WT/60)θWT · θCYP · eηCL (if CYP2C9*1/*1, θCYP = 1; if *1/*3, θCYP = 0.708); EC50 = θEC50 · θVKOR · eηEC50 (if VKORC1- 1639AA, θVKOR = 1; if GA, θVKOR = 2.01; V = θV; K(E0) = θK(E0); Emax = θEmax; E0 = θE0 · eηE0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Polymorphism, Genetic
/
Warfarin
/
Body Weight
/
Pharmacokinetics
/
Nonlinear Dynamics
/
International Normalized Ratio
/
Vitamin K Epoxide Reductases
/
Cytochrome P-450 CYP2C9
/
Genetics
Type of study:
Prognostic study
Limits:
Humans
Language:
Chinese
Journal:
Acta Pharmaceutica Sinica
Year:
2015
Type:
Article
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