Disposition of /sup 14/C tolrestat in laboratory animals and man

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5320593

Ferdinandi, E S; Hicks, D R; Cayen, M N

The disposition of the aldose reductase inhibitor tolrestat (T) was determined in the mouse, rat, dog, assemensis monkey, and man. Serum T and radioactivity ratios, and % of dose excreted after p.o. administration of /sup 14/C-T at a dose of 10 mk/kg (100 mg to man), are presented. Except for the rat and monkey, 55 to 95% of the urinary /sup 14/C was due to T and oxo-tolrestat (oxo-T, N-((5-(trifluoromethyl)-6-methoxy-1-napthalenyl)oxo-methyl)-N-methylglycine). Oxo-T is formed, in part, non-enzymatically from T; a potential intermediate in this transformation was detected in all the urine samples. In man and monkey, about 15% and 68%, respectively, of the urinary /sup 14/C was due to T-glucuronide. In rat urine, >90% of the /sup 14/C was due to polar metabolites; in bile, about 66% of the /sup 14/C was due to T. The composition of the serum /sup 14/C in the mouse and rat was determined. In conclusion, /sup 14/C-T was rapidly and well absorbed by all species. Except for the rat and dog, urine was the main excretion route for /sup 14/C. Urine/sup 14/ comprised mainly T, t-glucuronide of oxo-T in all the species except the rat.

• Research Organization: Ayerst Labs. Research Inc., Princeton, NJ
• OSTI ID: 5320593
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL VARIABILITY
BIOLOGICAL WASTES
BODY FLUIDS
CARBON 14 COMPOUNDS
CLEARANCE
DOGS
ENZYME INHIBITORS
EXCRETION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MAN
MATERIALS
METABOLISM
METABOLITES
MICE
MONKEYS
PRIMATES
RATS
RODENTS
TRACER TECHNIQUES
URINE
VERTEBRATES
WASTES