The effects of whole-body hyperthermia on the disposition and metabolism of Adriamycin were investigated in male New Zealand rabbits. Hyperthermia [rectal temperature, 42.3 ± 0.1° (S.D.)] was produced in nonacclimatized, unrestrained animals by placing them in a humidity (95%)- and temperature (34°)-regulated chamber. Normothermic controls (rectal temperature, 39.7 ± 0.1°) were maintained at ambient temperature and humidity. Adriamycin was administered i.v. to both groups over a 60-sec period at a dose of 5 mg/kg, and arterial blood samples were removed serially at several times up to 60 min. Animals were sacrificed with pentobarbital, and bladder urine, bile, and tissue samples were removed and immediately frozen until analyzed fluorometrically.
In general, the rate of clearance of Adriamycin from the plasma was similar in both groups; however, small but significant decreases in the distributive α phase were observed in the hyperthermic group. Analysis of tissue concentrations of Adriamycin, adriamycinol, and aglycones revealed significant increases only in skeletal muscle and duodenum of hyperthermic compared to normothermic rabbits. Urinary and biliary levels of Adriamycin and its metabolites were not different in the two groups, but the percentage of total urinary products attributable to adriamycinol was significantly higher in the hyperthermic group.
Plasma creatine phosphokinase activity and the respective brain and muscle isozymes were increased in animals following hyperthermia plus Adriamycin treatment as compared with pre-Adriamycin levels. Adriamycin treatment resulted in significant reductions in plasma calcium and significant increases in plasma aldolase in both experimental groups, but other parameters including lactic dehydrogenase, serum glutamic oxalacetic transaminase, alkaline phosphatase, phosphorus, magnesium, potassium, sodium, chloride, carbon dioxide, blood urea nitrogen, creatine, cholesterol, bilirubin, uric acid, and total protein remained within normal limits. Hyperglycemia was produced by the combination of whole-body hyperthermia and Adriamycin treatment.