Dexamethasone as a probe for CYP3A4 metabolism: evidence of gender effect.
Cancer Chemother Pharmacol
; 60(2): 305-8, 2007 Jul.
Article
em En
| MEDLINE
| ID: mdl-17124593
ABSTRACT
BACKGROUND:
A study was conducted to evaluate prospectively the correlation between docetaxel clearance and pharmacokinetics of dexamethasone previously obtained in 21 patients. PATIENTS ANDMETHODS:
Dexamethasone pharmacokinetics were performed in 17 patients 24 h before docetaxel treatment as monochemotherapy. Dexamethasone and docetaxel plasma concentrations were determined by HPLC methods. Determination of docetaxel unbound fraction in plasma was performed using microequilibrium dialysis.RESULTS:
Significant correlation was observed between observed plasma docetaxel clearances (CL(docetaxel)) and values predicted from dexamethasone plasma clearance (CL(dexa)), unbound plasma docetaxel fraction estimated from serum alpha1-acid glycoprotein level (fu(alpha1-AAG)), and hepatic metastasis status. However, after splitting of the prospective data set according to gender, no correlation was observed for males (R(2) = 0.08, NS, n = 10), then strong correlation was observed for females (R(2) = 0.78, P < 0.01, n = 7). Multivariate analysis was performed from data obtained in the women included in the first study and those of this prospective study (n = 18). Docetaxel CL was significantly correlated with CL(dexa) (P = 0.001) and fu(alpha1-AAG) (P = 0.01) according to the relationship (with +/-95% confidence intervals) CL(docetaxel) (l/h) = 1.92 (+/-0.94) x CL(dexa) (l/h) + 2.68 (+/-1.95) x fu(alpha1-AAG) (%) (R(2) = 0.68).CONCLUSION:
Dexamethasone may be used to predict docetaxel clearances in females, but not in males.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dexametasona
/
Antineoplásicos Hormonais
/
Sistema Enzimático do Citocromo P-450
/
Taxoides
/
Neoplasias
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Aspecto:
Determinantes_sociais_saude
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
França