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Population pharmacokinetics of metoprolol in Chinese post-PCI patients
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  • Hui Chen,
  • Huiwu Hong,
  • Wenjiao Zhao,
  • Huan Wang
Hui Chen
The shengli clinical Medical college of Fujian Medical University
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Huiwu Hong
The shengli clinical Medical college of Fujian Medical University
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Wenjiao Zhao
Fuzhou second Hospital
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Huan Wang
The shengli clinical Medical college of Fujian Medical University
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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.