Mechanism of renal excretion of carumonam in rats, rabbits, dogs, and monkeys.
The mechanism of the renal excretion of carumonam (CRMN) was investigated in rats, rabbits, dogs, and monkeys. Stop-flow analysis in dogs demonstrated that CRMN is exclusively excreted by glomerular filtration. There was no specific CRMN peak corresponding to the peak of p-aminohippuric acid (PAH) secretion or to the trough of Na+-K+ reabsorption in the stop-flow pattern. Although the PAH peak disappeared when probenecid was administered, the CRMN stop-flow pattern showed no change. In rabbits, however, the CRMN concentration peak corresponding with the PAH peak was detected in the stop-flow pattern; the CRMN peak disappeared when probenecid was administered. The pharmacokinetic parameters in plasma, such as the area under the concentration-time curve, the half-life, and the clearance rate, were affected by probenecid in rats, rabbits, and monkeys, but not in dogs. The results suggest that the renal excretion of CRMN in dogs takes place exclusively through glomerular filtration. In rats, rabbits, and monkeys, however, CRMN is excreted through both glomerular filtration and renal tubular secretion.
Central Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Y
Y
Kita
A
A
Imada
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001398:Aztreonam / Q000031:analogs & derivatives*; D004285:Dogs; D005260:Female; D007668:Kidney / Q000378:metabolism*; D007769:Lactams; D008252:Macaca fascicularis; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008813:Mice, Inbred ICR; D011339:Probenecid / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D000900:Anti-Bacterial Agents; D007769:Lactams; C044145:carumonam; D001398:Aztreonam; D011339:Probenecid