Influence of CYP2D6*5 and *10 polymorphism on the pharmacokinetics of nebivolol in healthy Chinese subjects.
What is known and objective: Nebivolol, a selective β1 adrenoreceptor antagonist, is predominantly metabolized by cytochrome P450 (CYP)2D6 and shows a wide interindividual variability in pharmacokinetics. The present study was conducted to evaluate the effects of the major CYP2D6 polymorphisms on ne...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 45; no. 4; pp. 632 - 638 |
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| Autores principales: | , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Aug2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=144405601&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 144405601 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Aug2020 vid: 45 iid: 4 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 144405601 144405601 144405601 10.1111/jcpt.13155 144405601 ppf: 632 ppct: 6 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: Influence of CYP2D6*5 and *10 polymorphism on the pharmacokinetics of nebivolol in healthy Chinese subjects. aug: au: Guo, Lifang Wang, Shumin Wan, Zirui Ni, Siyang Xu, Benshan Zhao, Xiuli Liu, Lihong affil: Pharmacy Department, Beijing Chao‐Yang Hospital, Capital Medical University, Beijing, China sug: subj: Nebivolol Hydrochloride Pharmacokinetics Polymorphism, Genetic Chinese Persons Human Genotype Chromatography, High Pressure Liquid Mass Spectrometry Unpaired T-Tests Analysis of Variance Nebivolol Hydrochloride Blood Polymorphism, Single Nucleotide ab: What is known and objective: Nebivolol, a selective β1 adrenoreceptor antagonist, is predominantly metabolized by cytochrome P450 (CYP)2D6 and shows a wide interindividual variability in pharmacokinetics. The present study was conducted to evaluate the effects of the major CYP2D6 polymorphisms on nebivolol disposition in healthy Chinese volunteers. Methods: Twenty‐eight volunteers were enrolled and classified as CYP2D6*1/*1, CYP2D6*1/*10, CYP2D6*10/*10 and CYP2D6*5 carriers according to their genotypes. The concentration of nebivolol was determined by high‐performance liquid chromatography‐tandem mass spectrometry. The association between the pharmacokinetic parameters and genotypes was evaluated using the unpaired t test or analysis of variance. Results and discussion: We evaluated the effects of CYP2D6*5 and *10 polymorphism on the pharmacokinetics of nebivolol. Plasma nebivolol peak concentration and area under the curve (AUC(0‐48 h) and AUC(0‐∞)) were significantly higher in subjects with CYP2D6*5 and CYP2D6*10/*10 polymorphism than those in subjects with wild‐type CYP2D6 (CYP2D6*1/*1), whereas its plasma clearance was significantly lower in the CYP2D6*10/*10 and CYP2D6*5 carriers. No significant differences in the peak time and terminal half‐life of nebivolol were observed among CYP2D6*10/*10, CYP2D6*1/*1 and CYP2D6*5 carriers. What is new and conclusion: Both CYP2D6*5 and *10 polymorphism altered the pharmacokinetics of nebivolol in healthy Chinese volunteers. Further studies are required to investigate the effects of these single‐nucleotide polymorphisms on the pharmacokinetics, pharmacodynamics and toxicity of nebivolol. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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