Allopurinol toxicity: its toxic organ-specificity between the liver and the kidney in the rat.

In this study, allopurinol toxicity was investigated in the liver and the kidney in the rat. Allopurinol was intraperitoneally administered to rats, once a day, for 1, 3 or 10 days, in doses of 3, 10, 30 and 100 mg/kg body weight/day. At the 24th hour after the last administration, the rat was sacrificed, and blood and tissue samples were taken for analyses. In doses of 30 mg/kg/day and more, decreases of the body weight and the liver weight were observed, while the kidney weight increased. The plasma activities of alkaline phosphatase, glutamic oxaloacetic and glutamic pyruvic transaminases showed no increases, while the blood urea nitrogen and creatinine increased. These changes were the most remarkable in the 3 day administration, whereas they approached the control level thereafter. In doses of 10 mg/kg/day and less, no significant changes were observed in comparison to the control. These results denote that the minimal toxic dose ranges between 10 and 30 mg/kg/day, and that the kidney is more sensitive than the liver. In addition, these results also denote that the renal and hepatic failures are reversively restored even when allopurinol is further administered later than the 3 day. This fact suggests not only that the capacity inactivating allopurinol in the body is increased, but also that the enzymatic induction in the allopurinol inactivation system is accelerated.