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.