الفهرس 
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Abstract
The present study was conducted to study pharmacokinetic and pharmacodynamic properties of DCX in Egyptian breast cancer patients and the interpatient variability of cytochrome3A4 activity, as estimated using urinary metabolites of exogenous cortisol.
To achieve this goal, fourteen female Patients with metastatic breast cancer, World Health Organization (WHO) performance status 0 to 2, were treated with 100mg/m2 single agent DCX, given every 21 days. Hydrocortisone 300 mg was administered intravenously to these patients 2 days before DCX treatment. CYP3A4 activity was determined by estimation of urinary metabolites of hydrocortisone. Pharmacokinetic blood samples were taken after administration of DCX. The correlation between pharmacokinetics, pharmacodymics and CYP3A4 activity were determined by the following:
1- .To phenotype these patients according to the CYP3A4 activity which estimated by the urinary metabolites of exogenous cortisol which detected by HPLC technique.
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2- To study the pharmacokinetic parameters of DCX in this patients as AUC, Cmax, t1/2 and clearance of the drug. DCX concentration in the plasma also detected by HPLC technique.
3- .Determination of the content of plasma α-1-acid glycoprotein by ELISA Kit.
4- Polymerase Chain Reaction (PCR) for CYP3A4 enzyme by:
• DNA extraction from whole blood using DNA extraction kit.
• DNA absorbance analysis by nanodrop.
• Ensure DNA intactness by agarose gel analysis.
The results of the study have revealed the following:
• After cortisol administration, total amount of 24-hour urinary 6β-OHF and FC were19.97 ±10.43 mg/24hr and 16.84 ±10.36 mg/24hr (mean ±SD) respectively. On the other hand, the 6β-OHF/FC ratio after cortisol administration was 1.86±1.933.
• The DCX CL was 19.9± 4.5 L/hr (mean ±SD), and AUC averaged 7.2 μg/ml.hr (range 5-8.8 μg/ml.hr). The volume of distribution was 65.6 ±28.6 L (mean
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±SD), Cmax was 2.4±0.6 μg/ml, T½α was 8.8 minute and T½β was 4.5 hr.
• Docetaxel PK parameters were correlated, significant correlation was only found between 6β-OHF/FC ratio and neutropenia (p = 0.04) and between 6β-OHF and C max (p = 0.04).
• Low CYP3A4 activity (6β-OHF/FC ratio <1) appears to be associated with higher response (p ≤ 0.0001, considered significant).
• Due to small sample size, polymorphism analysis couldn’t be completed.