Abstract
Abstract Aims: Metoprolol (MET) is widely used in post-PCI patient. This
study aimed to establishment a new population pharmacokinetic (PPK)
model of MET in Chinese post-PCI patients. Methods: Blood samples from
subjects were collected and the CYP2D6*10 genotyping was detected by
gene chip. The plasma concentration of MET was determined by LC-MS/MS.
The PPK model of MET was developed by using NONMEM method.
Pharmacogenetic analysis was carried out in the CYP2D6*10 genotyping.
Results: Based on the data of 43 patients with coronary heart disease
(CHD) after PCI, the final PPK model of MET was established as
follows: ; . A covariate analysis showed that only the CYP2D6 gene
mutation had a significantly effect on the MET clearance rate. The
CYP2D6*10 mutation could reduce the MET clearance rate. Compared with
the CYP2D6*1*1 genotype the CYP2D6*1*10 genotype decreased by 36.6%,
the CYP2D*10/*10 decreased by 70.7% and showing a gene dose effect.
Conclusions: The PPK model of MET established in this study is stable
and reliable, which can provide reference for individual administration
of MET. In Chinese patients with CHD after PCI, CYP2D6*10 gene mutation
is one of the important factors affecting the MET clearance rate.