The pharmacokinetics of epirubicin and docetaxel in combination in rats.
OBJECTIVE
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.


CONCLUSIONS
Concurrent treatment with EPI and DTX does not appear to cause any changes in the pharmacokinetics of the drugs in rats.
Sandström
M
M
Department of Pharmacy, Division of Biopharmaceutics and Pharmacokinetics, Uppsala University, Box 580, SE-751 23 Uppsala, Sweden.
Simonsen
L E
LE
Freijs
A
A
Karlsson
M O
MO
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000097:blood / Q000493:pharmacokinetics*; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012984:Software; D043823:Taxoids
D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D017239:Paclitaxel