Experimental studies on nephrotoxicity and pharmacokinetics of ly 146032 (daptomycin) in rats

B. Kreft*, C. De Wit, R. Krech, Reinhard Marre, E. Schulz, K. Sack

*Corresponding author for this work
9 Citations (Scopus)


The nephrotoxicity and pharmacokinetics of LY 146032 (daptomycin) were studied in an experimental rat model. Nephrotoxicity was assessed by measuring urinary loss of tubular cells and malate dehydrogenase. LY 146032 (10-250 mg/kg daily iv) led to a dose-dependent and reversible increase of cell elimination. The tubulo-toxic threshold dose is stated to be 10 mg/kg daily. Nephrotoxicity induced by LY 146032 can be reduced by coadministration of fosfomycin or D-glucaro-1·5-lactam, and enhanced by combination with tobramycin. LY 146032 accumulated in renal tissue during repeated administration. Electron microscopy revealed histopathological changes in the kidneys. Therefore the nephrotoxic potential of LY 146032 should be taken into consideration in clinical trials.

Original languageEnglish
JournalJournal of Antimicrobial Chemotherapy
Issue number4
Pages (from-to)635-643
Number of pages9
Publication statusPublished - 04.1990

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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