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.
Kim
S H
SH
College of Pharmacy, Seoul National University, Republic of Korea.
Kim
W B
WB
Kwon
J W
JW
Lee
M G
MG
D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D015780:Carbapenems / Q000009:adverse effects* / Q000493:pharmacokinetics; D004347:Drug Interactions; D007677:Kidney Function Tests; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D020011:Protective Agents / Q000627:therapeutic use*; D011817:Rabbits
D015780:Carbapenems; C099230:DA 1131; D020011:Protective Agents; C047207:N-benzoylalanine; D000409:Alanine