title: Absorption and disposition of N-(1, 1-dimethylethyl)-N'-[2-(4-pyridinyl)-4-pyrimidinyl]urea in rats and dogs.
abstract: N-(1, 1-Dimethylethyl)-N'-[2-(4-pyridinyl)-4-pyrimidinyl]urea, Win 40, 882, was eliminated from the blood stream of dogs by two apparent first-order processes with alpha- and beta-phase half-lives of 0.2 hr and 1.4 hr, respectively. Radioactivity of the administered dose was excreted by rats in the feces and via the kidneys; about 40-45% of the dose was recovered in the feces, with the remainder in the urine, over a six day period. One of the terminal methyl groups of the tert-butyl moiety of Win 40,882 is sequentially oxidized by the rat to the alcohol, aldehyde and carboxylic acid. In addition, some of the aldehyde was further metabolized to generate two different monohydroxylated aldehydic metabolites; these hydroxyaldehydes accounted for less than 10% of the dose administered. An unusual metabolic pattern was noted in the excretion of Win 40,882. Over 30% of the urinary metabolites contained the carboxaldehyde function; only8% of the urinary radioactivity was represented by the further oxidation of the aldehyde group to generate the carboxylic acid.
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D004285:Dogs; D005243:Feces / Q000032:analysis; D005260:Female; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity; D013997:Time Factors; D014018:Tissue Distribution; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D011743:Pyrimidines; D014508:Urea