Pharmacokinetics of a new carbapenem, DA-1131, after intravenous administration to rats with alloxan-induced diabetes mellitus.
Because physiological changes occurring in diabetes patients could alter the pharmacokinetics of drugs used to treat the disease, the pharmacokinetics and tissue distribution of DA-1131, a new carbapenem antibiotic, were investigated after 1-min intravenous (i.v.) administration of the drug, 50 mg kg-1, to control and alloxan-induced diabetes mellitus (AIDM) rats. The impaired kidney function was observed by pretreatment with alloxan based on physiological parameters of plasma, creatinine clearance, and the kidney microscopy. After 1-min i.v. infusion of DA-1131, the plasma concentrations of DA-1131 and the total area under the plasma concentration-time curve of DA-1131 from time zero to time infinity (AUC) increased significantly in the AIDM rats (7350 versus 4400 micrograms min mL-1) when compared with those in control rats. This was due to significantly slower total body clearance (Cl) of DA-1131 (6.80 versus 11.4 mL min-1 kg-1) in AIDM rats than that in control rats. The significantly slower Cl of DA-1131 in AIDM rats was due to significantly slower renal (2.62 versus 4.95 mL min-1 kg-1, because of the considerably decreased glomerular filtration rate of DA-1131) and nonrenal (3.99 versus 6.34 mL min-1 kg-1, possibly because of the considerably slower metabolism in rat liver and kidney) clearance in AIDM rats. The amount of DA-1131 recovered from each rat tissue studied was significantly higher in AIDM rats than that in control rats, however, the tissue to plasma ratios were not significantly different between the two groups of rats.
Kim
S H
SH
College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Gu, Republic of Korea.
Kim
W B
WB
Lee
M G
MG
D000496:Alloxan; D000818:Animals; D015780:Carbapenems / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D015780:Carbapenems; C099230:DA 1131; D000496:Alloxan