Influence of CYP2D6 genetic polymorphism on pharmacokinetics of metoprolol in Chinese population

Abstract

Abstract: AIM: To investigate the influence of CYP2D6 genetic polymorphism on pharmacokinetics of metoprolol in Chinese volunteers. METHODS: CYP2D6 genotypes were determined by genechips. Forty adult healthy Chinese volunteers were divided into the following four groups (n=10 in each group); Group 1: CYP2D6 *2W *10W, Group 2: CYP2D6 * 2H *10W or CYP2D6 *2M *10W, Group 3: CYP2D6 *2M *10H, Group 4: CYP2D6 *2M * 10M.After oral administration of 100 mg metoprolol, plasma and urine samples were collected from each subject over a 24-h period.The plasma and urine concentrations of metoprolol and its metabolite α-hydroxy metoprolol (HM) were determined by HPLC with fluorescence detection.RESULTS: The main pharmacokinetic parameters of metoprolol andHM in Group 2 were not significantly different from those in Group 1.In Group 3, t_1/2, AUC and C_max of metoprolol were significantly higher than those in Group 1, while t_1/2 of HM was 47.3% longer than that in Group 1 and AUC was 56.0% lower than that in Group 1.In Group 4, t_1/2, AUC and C_max of metoprolol were significantly higher than those in Group 1 and Group 3, respectively. While for HM, there was a significant difference compared with those in Group 1 and Group 3.The oral clearance and renal clearance in Group 3 and Group 4 were significantly lower than those in Group 1.The metabolic ratio (MR_0-24) in Group 3 and Group 4 were 1.82 and 3.96 times than that in Group 1, respectively.CONCLUSION: The present results show that CYP2D6 *2 has no influence on the pharmacokinetics of metoprolol, but CYP2D6 *10 reduces CYP2D6 activity which leads to the change of phenotype, and the homozygotes has more significant influence on the pharmacokinetics of metoprolol than the heterozygotes in Chinese population.

Key words: CYP2D6, Chinese population, metoprolol, α-hydroxy metoprolol, pharmacokinetics

CLC Number:

R969.1
R285

LI Qin, WANG Rui, GUO Ya, PEI Fei. Influence of CYP2D6 genetic polymorphism on pharmacokinetics of metoprolol in Chinese population[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(7): 796-802.

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