Effects of cilastatin on the pharmacokinetics of a new carbapenem, DA-1131, in rats, rabbits, and dogs.
DA-1131, a new carbapenem antibiotic, undergoes renal metabolism by renal dehydropeptidase I (DHP-I), located on the brush border of the proximal tubular cell. Species differences with regard to the effects of cilastatin, a renal DHP-I inhibitor, were investigated after a 1-min intravenous infusion of DA-1131, with or without cilastatin, to rats, rabbits, and dogs. After intravenous infusion, the nonrenal clearance (CL(NR)) of DA-1131 was significantly slower in rats (3.00 versus 8.01 ml/min/kg) and rabbits (2.41 versus 6.77 ml/min/kg) when the drug was coadministered with cilastatin; this could be due to the slower metabolism of DA-1131 by rat and rabbit kidney DHP-I. This indicated that renal metabolism of DA-1131 by renal DHP-I was inhibited by cilastatin. However, coadministration with cilastatin to dogs did not affect the CL(NR) of DA-1131.
Kim
S H
SH
College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Korea.
Kwon
J W
JW
Kim
W B
WB
Lee
M G
MG
D000818:Animals; D015780:Carbapenems / Q000493:pharmacokinetics*; D015377:Cilastatin / Q000494:pharmacology*; D004150:Dipeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004285:Dogs; D004347:Drug Interactions; D008657:Metabolic Clearance Rate; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D015780:Carbapenems; C099230:DA 1131; D011480:Protease Inhibitors; D015377:Cilastatin; D004150:Dipeptidases; C038937:dipeptidase