Pharmacokinetics and disposition of lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent, in rat and monkey.
14C-Labelled 1-(2,6-dimethylphenyl)-3-methylamidinourea hydrochloride (14C-WHR-1142A, lidamidine hydrochloride) was rapidly and quantitatively absorbed from the gastrointestinal tract of rat and monkey after a single oral dose of 5 mg/kg (base). Peak 14C levels occurred within 30 min and the radiolabel was found in both the plasma and cellular components of whole blood. The half-life of the parent compound was 30 min in rat and 1 h in the monkey. The label was essentially cleared from all tissues examined within 24 h in the rat. In both rat and monkey, the compound was extensively metabolized (greater than 90%) prior to excretion and eliminated primarily in the urine (95% of the 14C dose could be accounted for in urine within 24 h in the monkey and 65% within 24 h in the rat); about 15-20% of the dose was recovered in feces within 24 h in the rat. In rat, a significant portion of the dose was eliminated in bile, and enterohepatic recirculation of 14C excreted in bile occurred. In contrast, biliary elimination of 14C was not a major pathway in the monkey.
D000578:Amidines / Q000097:blood / Q000378:metabolism*; D000818:Animals; D000930:Antidiarrheals / Q000097:blood / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D005260:Female; D000882:Haplorhini; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D013045:Species Specificity; D014018:Tissue Distribution
D000578:Amidines; D000930:Antidiarrheals