No influence of CYP2D6*10 genotype and phenotype on the pharmacokinetics of nebivolol in healthy Chinese subjects. (27th July 2015)

• Record Type: Journal Article
• Authors: Luo, X.; Lei, Y.; He, L.; Liu, W.; Li, M.; Ran, L.; Yu, M.; Guo, X.; Yu, P.; Liu, Z.; Cheng, Z.
• Is Part Of: Journal of clinical pharmacy and therapeutics. Volume 40:Number 5(2015:Oct.)
• Page Start: 561
• Page End: 565
• Publication Date: 2015-07-27
• Subjects: Clinical pharmacology -- Periodicals; Chemotherapy -- Periodicals; 615
• DOI: 10.1111/jcpt.12310
• Languages: English
• ISSNs: 0269-4727

Abstract

<abstract abstract-type="main" id="jcpt12310-abs-0001"> <title>Summary</title> <sec id="jcpt12310-sec-0001" sec-type="section"> <title>What is known and objective</title> <p>Nebivolol, a clinically important antihypertensive drug, mainly metabolized by cytochrome P450 (CYP) 2D6, shows wide interindividual variability in pharmacokinetics. The <italic>CYP2D6*10</italic> 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 <italic>CYP2D6*10</italic> genotype and phenotype are associated with changes in the pharmacokinetics of nebivolol in Chinese subjects.</p> </sec> <sec id="jcpt12310-sec-0002" sec-type="section"> <title>Methods</title> <p>Twenty‐four healthy subjects were divided into three groups according to <italic>CYP2D6*1/*1</italic> (<italic>n</italic> = 7), <italic>CYP2D6*1/*10</italic> (<italic>n</italic> = 5) and <italic>CYP2D6*10/*10</italic> (<italic>n</italic> = 12) genotypes. The <italic>*1/*1</italic> homozygotes and <italic>*1/*10</italic> heterozygotes were C allele carriers. All subjects received oral single dose of nebivolol and dextromethorphan. Blood and urine samples were gathered at various times.</p> </sec> <sec id="jcpt12310-sec-0003" sec-type="section"> <title>Results</title> <p>There were no statistically significant differences in the pharmacokinetics of nebivolol between the three <italic>CYP2D6*10</italic> genotypes, and no gene‐dose effect was seen. The pharmacokinetic parameters of <italic>CYP2D6*10/*10</italic> subjects were also similar to those of <italic>CYP2D6*1</italic> carriers. A weak relationship between CYP2D6 phenotype and nebivolol clearance was found.</p> </sec> <sec id="jcpt12310-sec-0004" sec-type="section"> <title>What is new and conclusion</title> <p>The <italic>CYP2D6*10</italic> genotype and phenotype were not associated with significant alterations in the pharmacokinetics of nebivolol. <italic>CYP2D6*10</italic> alone does not account for the large interindividual differences observed in the disposition of nebivolol among Chinese healthy subjects.</p> </sec> </abstract>