Influence of CYP2D6*5 and *10 polymorphism on the pharmacokinetics of nebivolol in healthy Chinese subjects.
J Clin Pharm Ther
; 45(4): 632-637, 2020 Aug.
Article
em En
| MEDLINE
| ID: mdl-32379356
ABSTRACT
WHAT IS KNOWN AND OBJECTIVE:
Nebivolol, a selective ß1 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 ANDDISCUSSION:
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 ANDCONCLUSION:
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
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Citocromo P-450 CYP2D6
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Povo Asiático
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Nebivolol
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article