The pharmacokinetics of epirubicin and docetaxel in combination in rats

Purpose: The aim of the present study was to investigate possible pharmacok inetic interactions between epirubicin (EPI) and docetaxel (DTX) in rats. M ethods: Male Sprague Dawley rats (n = 36) were used in the study. They rece ived 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. Blo od samples were collected at Various time-points between 3 min and 45 h aft er dose administration. DTX and EPI plasma concentrations were determined b y HPLC analysis. Pharmacokinetic evaluation was carried out using the NONME M program. Results: A three-compartment model best described the concentrat ion-time profiles for EPI. Clearance (CL), intercompartmental clearances (Q 2 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 su fficient to describe the DTX data. CL. intercompartmental clearance (Q), VI 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 ei ther 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 dru gs in rats.