PHARMACOKINETICS OF DOXORUBICIN AND EPIRUBICIN IN MICE DURING CHLORPROMAZINE-INDUCED HYPOTHERMIA

Blood concentrations of doxo- and epirubicin were studied in mice afte r i.v. or i.p. administration under normal and hypothermic conditions. The animals either were pretreated i.p. with chlorpromazine at 15 mg/ kg and allowed to cool to a rectal temperature of 28 degrees C or were given saline i.p. with their rectal temperature remaining at 37 degre es C. The anthracyclines were 14-C-14-labeled and were given at a dose of 0.85 mg/kg. Blood samples were taken at 5, 15, and 25 min and 2, 6 , 24, and 48 hours after injection and were analyzed by liquid scintil lation counting. The blood concentration related to time was similar f or the two anthracyclines. The peak concentration was highest for i.v. administration and was higher for the hypothermic groups. The peak co ncentration and the area under the curve were highest under hypothermi c conditions. The terminal half-life was longer after i.p. administrat ion. The ratio calculated for the blood concentration under hypothermi c/normothermic conditions over time was substantially increased after i.p. administration, the increase being most pronounced for epirubicin . The pharmacokinetic characteristics found might be related to the an thracycline toxicity encountered in tumor-inoculated mice treated at d ifferent body temperatures.