Effects of CYP2D610 on plasma trough concentration of metoprolol in patients with coronary artery disease.
10.12122/j.issn.1673-4254.2019.03.11
- Author:
Qian ZHU
1
;
Weihua LAI
2
;
Liwen LI
3
;
Hanping LI
4
;
Shilong ZHONG
1
Author Information
1. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
2. Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
3. Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
4. Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
- Publication Type:Journal Article
- Keywords:
CYP2D6*10;
blood pressure;
heart rate;
metoprolol;
trough concentration
- MeSH:
Adrenergic beta-Antagonists;
Chromatography, Liquid;
Coronary Artery Disease;
Cytochrome P-450 CYP2D6;
Genotype;
Humans;
Metoprolol;
Tandem Mass Spectrometry
- From:
Journal of Southern Medical University
2019;39(3):328-336
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To study the effect of CYP2D610 (c.100 C>T) on plasma trough concentrations of metoprolol and its metabolite α-hydroxy metoprolol, blood pressure and heart rate in patients with coronary artery disease.
METHODS:The patients with coronary artery disease taking metoprolol tablets (=128) and those taking metoprolol sustained-release tablets (=126) were genotyped for CYP2D610 using Taqman real-time quantitative PCR. The trough concentrations of metoprolol and α-hydroxy metoprolol were determined with UPLC-MS/MS, and the dose-normalized concentrations (C/D) were compared among the patients with different CYP2D610 genotypes in both groups. Resting blood pressure and heart rate were recorded in all the patients when the concentration of metoprolol reached the steady state and were compared among the patients with different genotypes.
RESULTS:In patients taking metoprolol sustained-release tablets, the plasma trough concentration of α-hydroxy metoprolol was significantly associated with the systolic blood pressure (=0.0204). The CYP2D610 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol ( < 0.01) in patients receiving metoprolol in both formulations, and in both groups, the C/D of metoprolol was significantly higher in the patients with a TT genotype than in those with a CC or CT genotype ( < 0.01); compared with those with the CT genotype, the patients with the TT genotype had a significantly lower C/D of α-hydroxy metoprolol ( < 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (=0.0281) and TT (=0.0196) genotypes had lower diastolic blood pressure than patients with the CC genotypes, but the systolic blood pressure or heart rate did not differ significantly among them.
CONCLUSIONS:CYP2D610T allele mutation can reduce the metabolism of metoprolol, increase the C/D of metoprolol and decrease the C/D of α-metoprolol and diastolic blood pressure in patients with coronary artery disease, but CYP2D610 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.
