Erschienen in:
01.07.2007 | Short Communication
Dexamethasone as a probe for CYP3A4 metabolism: evidence of gender effect
verfasst von:
F. Puisset, E. Chatelut, A. Sparreboom, J.-P. Delord, D. Berchery, I. Lochon, T. Lafont, H. Roché
Erschienen in:
Cancer Chemotherapy and Pharmacology
|
Ausgabe 2/2007
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Abstract
Background
A study was conducted to evaluate prospectively the correlation between docetaxel clearance and pharmacokinetics of dexamethasone previously obtained in 21 patients.
Patients and methods
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 (CLdocetaxel) and values predicted from dexamethasone plasma clearance (CLdexa), unbound plasma docetaxel fraction estimated from serum α1-acid glycoprotein level (fuα1–AAG), and hepatic metastasis status. However, after splitting of the prospective data set according to gender, no correlation was observed for males (R² = 0.08, NS, n = 10), then strong correlation was observed for females (R² = 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 CLdexa (P = 0.001) and fuα1–AAG (P = 0.01) according to the relationship (with ±95% confidence intervals): CLdocetaxel (l/h) = 1.92 (±0.94) × CLdexa (l/h) + 2.68 (±1.95) × fuα1–AAG (%) (R² = 0.68).
Conclusion
Dexamethasone may be used to predict docetaxel clearances in females, but not in males.