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

Biopharm Drug Dispos. 1999 Apr;20(3):125-9. doi: 10.1002/(sici)1099-081x(199904)20:3<125::aid-bdd163>3.0.co;2-v.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / therapeutic use
  • Animals
  • Carbapenems / adverse effects*
  • Carbapenems / pharmacokinetics
  • Drug Interactions
  • Kidney Function Tests
  • Kidney Tubular Necrosis, Acute / chemically induced
  • Kidney Tubular Necrosis, Acute / prevention & control*
  • Male
  • Protective Agents / therapeutic use*
  • Rabbits

Substances

  • Carbapenems
  • DA 1131
  • Protective Agents
  • N-benzoylalanine
  • Alanine