title: No influence of CYP2D6*10 genotype and phenotype on the pharmacokinetics of nebivolol in healthy Chinese subjects.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Life Sciences, Central South University, Changsha, China.|Research Institute of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.affiliation: Research Institute of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Central South University, Changsha, China.|Haikou People's Hospital and Affiliated Haikou Hospital of Xiangya Medical School, Central South University, Haikou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Research Institute of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: L
authors.initials: L
authors.lastname: He
authors.affiliation: Research Institute of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: Research Institute of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Hunan Tiger Xiangya R&D Co., Ltd, Changsha, China.
authors.forename: L
authors.initials: L
authors.lastname: Ran
authors.affiliation: Hunan Tiger Xiangya R&D Co., Ltd, Changsha, China.
authors.forename: M
authors.initials: M
authors.lastname: Yu
authors.affiliation: Hunan Tiger Xiangya R&D Co., Ltd, Changsha, China.
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.affiliation: Research Institute of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: P
authors.initials: P
authors.lastname: Yu
authors.affiliation: Hunan Tiger Xiangya R&D Co., Ltd, Changsha, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Research Institute of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Cheng
keywords: CYP2D6*10; dextromethorphan; genotype; nebivolol; pharmacokinetics; phenotype