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.