Tolrestat kinetics

Journal Article · Mon Oct 01 00:00:00 EDT 1984 · Clin. Pharmacol. Ther.; (United States)

DOI:https://doi.org/10.1038/clpt.1984.209· OSTI ID:5763196

Hicks, D R; Kraml, M; Cayen, M N; Dubuc, J; Ryder, S; Dvornik, D

The kinetics of tolrestat, a potent inhibitor of aldose reductase, were examined. Serum concentrations of tolrestat and of total /sup 14/C were measured after dosing normal subjects and subjects with diabetes with /sup 14/C-labeled tolrestat. In normal subjects, tolrestat was rapidly absorbed and disappearance from serum was biphasic. Distribution and elimination t 1/2s were approximately 2 and 10 to 12 hr, respectively, after single and multiple doses. Unchanged tolrestat accounted for the major portion of /sup 14/C in serum. Radioactivity was rapidly and completely excreted in urine and feces in an approximate ratio of 2:1. Findings were much the same in subjects with diabetes. In normal subjects, the kinetics of oral tolrestat were independent of dose in the 10 to 800 mg range. Repetitive dosing did not result in unexpected cumulation. Tolrestat was more than 99% bound to serum protein; it did not compete with warfarin for binding sites but was displaced to some extent by high concentrations of tolbutamide or salicylate.

• Research Organization: Ayerst Labs., Princeton, NJ
• OSTI ID: 5763196
• Journal Information: Clin. Pharmacol. Ther.; (United States), Vol. 36:4
• Country of Publication: United States
• Language: English

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