Intraindividual and interindividual variabilities in endogenous cortisol 6ß-hydroxylation clearance as an index for in vivo CYP3A phenotyping in humans.
Drug Metab Dispos
; 41(2): 475-9, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-23175666
ABSTRACT
This study was designed to evaluate the in vivo activity of cytochrome P450 3A (CYP3A) in 49 healthy Japanese subjects aged 22-58 years using endogenous cortisol 6ß-hydroxylation clearance [CLm(6ß)], a novel biomarker for CYP3A phenotyping. CLm(6ß) in the 49 healthy subjects was 2.40 ± 0.79 ml/min with an approximately 4-fold interindividual variability of CYP3A activity. The mean clearance in the 24 women was 2.50 ± 0.89 ml/min; the value in the women was higher than in the 25 men (2.30 ± 0.69 ml/min) by approximately 9%. We also measured the change of CLm(6ß) in 14 healthy subjects in the morning at 1000-1200 every 2 or 3 days over a period of 36-53 days and observed a 1.5-fold to 3.4-fold day-to-day intraindividual variability in the CYP3A activity. The mean value for CLm(6ß) in each subject for 36-53 days was 2.54 ± 0.76 ml/min (n = 14). We also evaluated the CLm(6ß) every 2 hours from 800-2000 in 26 healthy subjects. The within-day intraindividual clearance variability was 1.1-fold to 2.5-fold (2.45 ± 0.91 ml/min, n = 26). No characteristic diurnal rhythms were observed in the in vivo activity of CYP3A.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Hidrocortisona
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Citocromo P-450 CYP3A
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article