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  • Title: No influence of CYP2D6*10 genotype and phenotype on the pharmacokinetics of nebivolol in healthy Chinese subjects.
    Author: Luo X, Lei Y, He L, Liu W, Li M, Ran L, Yu M, Guo X, Yu P, Liu Z, Cheng Z.
    Journal: J Clin Pharm Ther; 2015 Oct; 40(5):561-565. PubMed ID: 26214065.
    Abstract:
    WHAT IS KNOWN AND OBJECTIVE: Nebivolol, a clinically important antihypertensive drug, mainly metabolized by cytochrome P450 (CYP) 2D6, shows wide interindividual variability in pharmacokinetics. The CYP2D6*10 allele (100C>T; rs1065852), present at a high frequency in the Chinese population, is associated with alteration in the pharmacokinetics of many drugs, but its effect on the pharmacokinetics of nebivolol is unknown. The aim of our study was to investigate whether the CYP2D6*10 genotype and phenotype are associated with changes in the pharmacokinetics of nebivolol in Chinese subjects. METHODS: Twenty-four healthy subjects were divided into three groups according to CYP2D6*1/*1 (n = 7), CYP2D6*1/*10 (n = 5) and CYP2D6*10/*10 (n = 12) genotypes. The *1/*1 homozygotes and *1/*10 heterozygotes were C allele carriers. All subjects received oral single dose of nebivolol and dextromethorphan. Blood and urine samples were gathered at various times. RESULTS: There were no statistically significant differences in the pharmacokinetics of nebivolol between the three CYP2D6*10 genotypes, and no gene-dose effect was seen. The pharmacokinetic parameters of CYP2D6*10/*10 subjects were also similar to those of CYP2D6*1 carriers. A weak relationship between CYP2D6 phenotype and nebivolol clearance was found. WHAT IS NEW AND CONCLUSION: The CYP2D6*10 genotype and phenotype were not associated with significant alterations in the pharmacokinetics of nebivolol. CYP2D6*10 alone does not account for the large interindividual differences observed in the disposition of nebivolol among Chinese healthy subjects.
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