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- W2395541708 abstract "The metabolic disposition and pharmacokinetics of the aldose reductase inhibitor tolrestat were studied in rats, dogs, and assamese and capuchin monkeys. In addition, the ocular penetration of tolrestat was examined in rabbits. The bioavailability of tolrestat was 81% in rats and 68% in dogs. In contrast to rats, a major proportion of the serum 14C in dogs and monkeys was due to unchanged drug. The terminal elimination half-life of tolrestat in serum was 3.5 hr in rats, 11 hr in dogs, and 9 hr in monkeys; in both dogs and monkeys, the total body clearance was 200 ml/kg X hr, and the volume of distribution was 3 liters/kg. In rats and dogs, serum tolrestat concentrations were similar after single and multiple po doses, and were linearly dose-related up to 25 mg/kg, but increased disproportionately at higher doses. Tolrestat was at least 98% bound to rat and dog serum proteins. Except for organs associated with absorption and elimination, tissue 14C levels were lower than in serum of rats and capuchin monkeys, and there was no tissue 14C accumulation. The 14C from topically applied 14C-tolrestat readily penetrated into the eyes of rabbits. Liver microsomal cytochrome P-450 was virtually unaltered in tolrestat-treated rats. Tolrestat (and/or its metabolites) underwent enterohepatic circulation in rats. Most of the 14C from 14C-tolrestat administered po and iv to rats and dogs was excreted in the feces. Based on 14C excretion, the absorption of tolrestat was 84% in rats and 82% in dogs.(ABSTRACT TRUNCATED AT 250 WORDS)" @default.
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- W2395541708 date "1985-07-01" @default.
- W2395541708 modified "2023-09-23" @default.
- W2395541708 title "Metabolic disposition and pharmacokinetics of the aldose reductase inhibitor tolrestat in rats, dogs, and monkeys." @default.
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