Nephroprotective effect of betamipron on a new carbapenem, DA-1131, in rabbits

The nephroprotective effect of betamipron (200 mg/kg) was evaluated after intravenous administration of a high dose of DA-1131 (200 mg/kg) to rabbits. Extensive tubular necrosis was observed without betamipron but the necrosis was not observed with betamipron at 8 h after intravenous administration of DA-1131 based on kidney microscopy. By treatment with betamipron, the amounts and tissue to plasma (T/P) ratios of DA-1131 in renal cortex and whole kidney decreased significantly (65-91% decrease) at both 30 min and 2 h after intravenous administration of the drug to rabbits. This indicated that the accumulation of DA-1131 in rabbit renal cortex and whole kidney was inhibited by betamipron. This resulted in significantly greater percentages of intravenous DA-1131 excreted in urine as unchanged drug, 60.9 versus 40.1%, and significantly faster renal clearance (Cl(r)) of DA-1131 (6.10 versus 3.22 mL/min/kg) by treatment with betamipron. By treatment with betamipron, the amounts and T/P ratios of DA-1131 in renal cortex and whole kidney decreased significantly from 30 min and the renal function remained intact at 8 h after intravenous administration of DA-1131. The above data suggested that the nephroprotective effect of betamipron was fast and persisted for a long period of time in rabbits.