700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ ReadersThis Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)
Research Article Open Access
Purpose: To study the correlation between pharmacokinetics & pharmacodynamic of docetaxel and CYP3A4 activity in Egyptian cancer patients.
Patients and methods: Fourteen Egyptian female Patients with metastatic breast cancer, World Health Organization (WHO) performance status 0 to 2, had received prior chemotherapy regimen, were treated with single-agent docetaxel (100 mg/m2), given every 21 days. Hydrocortisone 300 mg IV was administered 2 days before docetaxel treatment and Cytochrome 3A4 activity was determined by measuring the level of urinary metabolites of 6β-hydroxy cortisol (6β-OHF) and cortisol (FC). For the pharmacokinetic study, Blood samples were taken before and after IV infusion for 1 hr of 100 mg/m2 docetaxel. The level of the drug was determined using HPLC and the correlation between pharmacokinetics and CYP3A4 activity were determined.
Results: After cortisol administration, the total amount of 24-hour urinary 6β-OHF and FC were19.97 ± 10.43 and 16.84 ± 10.36 mg/24 h (mean ± SD) respectively. On the other hand, the 6β-OHF/FC ratio after cortisol administration was 1.86 ± 1.933. The pharmacokinetic parameters of docetaxel were clearance 19.9 ± 4.5 L/hr, the volume of distribution 65.6 ± 28.6 L (mean ± SD) and AUC 7.2 μg/ml.hr (range 5-8.8 μg/ml.hr) ± SD). A significant correlation was found between 6β-OHF/FC ratio and neutropenia (p=0.04) in addition correlation between 6β-OHF and Cmax (p=0.04).
Conclusion: The interpatient variability of CYP3A4 activity in each patient could be predicted by measuring the total amount of 24 hour urinary 63-OHF after cortisol administration. Individualized dosing to optimize drug exposure for each patient could be performed based on this method. A farther study of fixed versus individualized dosing of docetaxel is needed to determine whether individualized chemotherapy with the application of this method can reduce PK and toxicity variability.
Docetaxel pharmacokinetic, CYP3A4 activity, Neutropenia, Response, Applied Biopharmaceutics, Clinical Pharmacology