Habekacin: nephrotoxicity, pharmacokinetics and prophylactic efficacy in rats.
1-N[(S)-4-amino-2-hydroxybutyryl]-kanamycin B (habekacin), a new aminoglycoside antibiotic found in 1973 was tested for its nephrotoxicity, pharmacokinetics and prophylactic efficacy in 351 female rats. Increased urinary elimination of tubule cells and malate dehydrogenase ( MDH) demonstrated tubulotoxicity even at the minimal dosage of 2.5 mg/kg/d. At high dosages (100 or 50 mg/kg/d) habekacin produced more tubule damage than dibekacin. At lower dosages (20, 10 or 5 mg/kg/d) both aminoglycosides showed similar effects. Additionally, possible glomerular lesions were found at high dosages (100 mg/kg/d) as indicated by proteinuria, CAF (cellulose acetate foil)-electrophoresis of the urinary protein and raised albumin/globulin ratio. - Pharmacological studies revealed serum concentrations similar to dibekacin, in renal tissue, however, the concentrations of habekacin were much higher than those of dibekacin. - In experimental E. coli pyelonephritis, 9 single doses of habekacin or dibekacin (5 mg/kg) given prophylactically reduced the bacterial counts significantly; a single dose of the antibiotics (5 mg/kg) was slightly effective.[1]References
- Habekacin: nephrotoxicity, pharmacokinetics and prophylactic efficacy in rats. Stewens, J., Marre, R., Engelbart, K., Schulz, E., Sack, K. Arzneimittel-Forschung. (1985) [Pubmed]
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