Distribution of tetrahydrouridine in experimental animals.
2-14C-tetrahydrouridine was prepared and used to determine the serum levels and excretion of tetrahydrouridine by varous experimental animals. In mice injected ip with the agent (50 mg/kg), the serum level of tetrahydrouridine was maximum (76 mug/ml) at 15 minutes. For rats injected with the same dose, the tetrahydrouridine content of serum was greatest (58 mug/ml) at 30 minutes. Within 3 hours, the serum content of the drug in both mice and rats fell to less than 10% of the maximum. The kidneys of mice selectively accumulated tetrahydrouridine; the concentration rose to 275 mug/g at 1 hour after injection. Nearly all of the dose was excreted unchanged in the urine of mice and rats in 24 hours. For a dog and a monkey given an iv dose (50 mg/kg) of tetrahydrouridine, serum levels of the agent were 210 and 200 mug/ml, respectively, at 5 minutes. The apparent half-lives for the initial phase of disappearance were 18 and 20 minutes and those for the later phase were 65 and 70 minutes, respectively. In 24 hours the dog and monkey excreted most of the dose as unchanged tetrahydrouridine. No metabolites were detected in the biologic samples from either species.
D000818:Animals; D004285:Dogs; D005260:Female; D000882:Haplorhini; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D013154:Spleen / Q000378:metabolism; D013767:Tetrahydrouridine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013997:Time Factors; D014529:Uridine / Q000031:analogs & derivatives*
D013767:Tetrahydrouridine; D014529:Uridine