title: Effect of probenecid on the renal excretion mechanism of a new carbapenem, DA-1131, in rats and rabbits.
abstract: The effects of probenecid, an anion transport inhibitor, on the renal excretion mechanism of a new anionic carbapenem, DA-1131, were investigated after a 1-min intravenous infusion of DA-1131 at 100 mg/kg of body weight to rabbits and 50 mg/kg to rats with or without probenecid at 50 mg/kg for both species. In control rabbits, the renal clearance (CLR) of DA-1131 and the glomerular filtration rate based on creatinine clearance (CLCR) were 6.14 +/- 2.09 and 2.26 +/- 0.589 ml/min/kg, respectively. When considering the less than 10% plasma protein binding of DA-1131 in rabbits, renal tubular secretion of DA-1131 was observed in rabbits. The CLR of DA-1131 (3. 87 +/- 0.543 ml/min/kg) decreased significantly with treatment with probenecid in rabbits, indicating that the renal tubular secretion of DA-1131 was inhibited by probenecid. However, in control rats, the CLR of DA-1131 (5.80 +/- 1.94 ml/min/kg) was comparable to the CLCR (4.29 +/- 1.64 ml/min/kg), indicating that DA-1131 was mainly excreted by glomerular filtration in rats. Therefore, it could be expected that the CLR of DA-1131 could not be affected by treatment with probenecid in rats; this was proved by a similar CLR of DA-1131 with treatment with (6.93 +/- 0.675 ml/min/kg) or without (5.80 +/- 1.94 ml/min/kg) probenecid. Therefore, the renal secretion of DA-1131 is a factor in rabbits but is not a factor in rats.
authors.affiliation: College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: W B
authors.initials: WB
authors.lastname: Kim
authors.forename: M G
authors.initials: MG
authors.lastname: Lee
mesh_terms: D000818:Animals; D019540:Area Under Curve; D015780:Carbapenems / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D007275:Injections, Intravenous; D008297:Male; D011339:Probenecid / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015780:Carbapenems; C099230:DA 1131; D003404:Creatinine; D011339:Probenecid