Qian Zhu1,2, Weihua Lai3, Liwen Li4, Hanping Li2, Shilong Zhong1,2,3. 1. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. 2. 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. 3. Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China. 4. Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Abstract
OBJECTIVE: To study the effect of CYP2D6*10 (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 (n=128) and those taking metoprolol sustained-release tablets (n=126) were genotyped for CYP2D6*10 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 CYP2D6*10 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 (P=0.0204). The CYP2D6*10 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol (P < 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 (P < 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 (P < 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (P=0.0281) and TT (P=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: CYP2D6*10T 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 CYP2D6*10 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.
OBJECTIVE: To study the effect of CYP2D6*10 (c.100 C&gt;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 (n=128) and those taking metoprolol sustained-release tablets (n=126) were genotyped for CYP2D6*10 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 CYP2D6*10 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 (P=0.0204). The CYP2D6*10 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol (P &lt; 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 (P &lt; 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 (P &lt; 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (P=0.0281) and TT (P=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:CYP2D6*10T 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 CYP2D6*10 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.
Authors: Michael Herman; Jennifer Donovan; Maichi Tran; Brigid McKenna; Joel M Gore; Robert J Goldberg; Dennis A Tighe Journal: Am Heart J Date: 2009-09 Impact factor: 4.749
Authors: I S Hamadeh; T Y Langaee; R Dwivedi; S Garcia; B M Burkley; T C Skaar; A B Chapman; J G Gums; S T Turner; Y Gong; R M Cooper-DeHoff; J A Johnson Journal: Clin Pharmacol Ther Date: 2014-03-17 Impact factor: 6.875