PHARMACOKINETIC AND TISSUE DISTRIBUTION CHANGES OF ADRIAMYCIN AND ADRIAMYCINOL AFTER INTRAVENOUS ADMINISTRATION OF ADRIAMYCIN TO ALLOXAN-INDUCED DIABETES-MELLITUS RATS

The pharmacokinetic and tissue distribution changes of adriamycin (ADM) were investigated after intravenous (i.v.) administration of ADM, 16 mg/kg, to the control rats and alloxan-induced diabetes mellitus rats (AIDRs). After 1 min i.v. infusion of ADM, apparent 'constant' plasma levels of ADM were maintained from 2 to 12 h in the AIDRs, whereas the levels were detected only up to 3 h in the control rats. Adriamycinol was detected only up to 1 and 5 min for the control rats and AIDRs, respectively, with significantly higher levels in the AIDRs. In tissue distribution studies, the amount of ADM obtained from the heart, lung, stomach, liver, small intestine, large intestine, fat, and lymph nodes were significantly higher in the AIDRs than that in the control rats. The tissue to plasma ratios of the liver, fat, and muscle also increased significantly in the AIDRs than those in the control rats. The amount of adriamycinol obtained from the lung, kidney, and liver was significantly higher in the AIDRs. All 7 control rats survived longer than 48 h, however 7 out of 9 AIDRs died between 36-48 h after i.v. administration of ADM, suggesting that the i.v. doses of ADM in diabetes mellitus patients may need to be modified if the present rat data could be extrapolated to human.