Effects of CYP3A4*1G and CYP3A5*3 polymorphisms on pharmacokinetics of tylerdipine hydrochloride in healthy Chinese subjects.
Xenobiotica
; 49(3): 375-380, 2019 Mar.
Article
en En
| MEDLINE
| ID: mdl-29521134
ABSTRACT
The aim of this analysis was to explore the influence of CYP3A4*1G and CYP3A5*3 polymorphisms on the pharmacokinetics of tylerdipine in healthy Chinese subjects. A total of 64 and 63 healthy Chinese subjects were included and identified as the genotypes of CYP3A4*1G and CYP3A5*3, respectively. Plasma samples were collected for up to 120 h post-dose to characterize the pharmacokinetic profile following single oral dose of the drug (5, 15, 20, 25 and 30 mg). Plasma levels were measured by a high-performance liquid chromatography-mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated using non-compartmental method. The maximum concentration (Cmax) and the area under the curve (AUC0-24 h) were all corrected by the dose given. In the wild-type group, the mean dose-corrected AUC0-24 h was 1.35-fold larger than in CYP3A4*1G carriers (p = .018). Among the three CYP3A5 genotypes, there showed significantly difference (p = .008) in the t1/2, but no significant difference was observed for the AUC0-24 h and Cmax. In subjects with the CYP3A5*3/*3 genotype, the mean t1/2 was 1.35-fold higher than in CYP3A5*1/*1 group (p = .007). And the t1/2 in CYP3A5*3 carriers also was 1.32-fold higher than in the wild-type group (p = .004). CYP3A4*1G and CYP3A5*3 polymorphisms may influence tylerdipine pharmacokinetic in healthy Chinese subjects.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
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Bloqueadores de los Canales de Calcio
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Citocromo P-450 CYP3A
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Nitrobencenos
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Xenobiotica
Año:
2019
Tipo del documento:
Article
País de afiliación:
China