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The pharmacokinetics of epirubicin and docetaxel in combination in rats
M Sandström1, L E Simonsen, A Freijs
1Department of Pharmacy, Division of Biopharmaceutics and Pharmacokinetics, Uppsala University, Box 580, SE-751 23 Uppsala, Sweden.
Purpose:
The aim of the present study was to investigate possible pharmacokinetic interactions between epirubicin (EPI) and docetaxel (DTX) in rats.
Methods:
Male Sprague Dawley rats (n = 36) were used in the study. They received either DTX (5 mg/kg, n = 9), EPI (3.5 mg/kg, n = 13), or a combination (5 mg/kg + 3.5 mg/kg, n = 14), administered as intravenous bolus doses. Blood samples were collected at various time-points between 3 min and 45 h after dose administration. DTX and EPI plasma concentrations were determined by HPLC analysis. Pharmacokinetic evaluation was carried out using the NONMEM program.
Results:
A three-compartment model best described the concentration-time profiles for EPI. Clearance (CL), intercompartmental clearances (Q2 and Q3), central (V1) and peripheral (V2 and V3) volumes of distribution were estimated as 3. 57 l/h per kg, 5.01 l/h per kg, 12.48 l/h per kg, 0.805 l/kg, 3.67 l/kg and 158 l/kg, respectively. A two-compartment model was sufficient to describe the DTX data. CL, intercompartmental clearance (Q), V1 and V2 for DTX were estimated as 7.3 l/h per kg, 4. 6 l/h per kg, 0.69 l/kg and 2.6 l/kg, respectively. No significant change in the disposition of either drug was found when they were administered in combination compared to when they were given singly.
Conclusion:
Concurrent treatment with EPI and DTX does not appear to cause any changes in the pharmacokinetics of the drugs in rats.