Key result
CYP2D6*10 mutation linked to up to ~71% lower metoprolol clearance in post-PCI patients.
Why the study?
A population pharmacokinetic model of metoprolol in Chinese post-PCI patients was lacking, and the impact of CYP2D6*10 genotype on metoprolol clearance was unclear.
Does CYP2D6*10 gene mutation affect the clearance rate of metoprolol in Chinese post-PCI patients?
Observational (n=43)
Does CYP2D6*10 gene mutation affect the clearance rate of metoprolol in Chinese post-PCI patients?
In Chinese post-PCI patients, the CYP2D6*10 gene mutation significantly reduces metoprolol clearance in a gene-dose dependent manner, highlighting the potential utility of genotype-guided dosing.
May warrant genotype-informed dosing caution in Chinese post-PCI patients; leaves open randomized confirmation of clinical utility.
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.
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Chen et al. (2020) conducted an observational in Coronary heart disease after PCI (n=43). CYP2D6*10 gene mutation vs. CYP2D6*1*1 genotype was evaluated on Metoprolol clearance rate. The CYP2D6*10 mutation significantly reduced metoprolol clearance in Chinese post-PCI patients, decreasing by 36.6% for the *1/*10 genotype and 70.7% for the *10/*10 genotype compared to *1/*1.
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