fortimicin-a-sulfate and Kidney-Diseases

The nephrotoxicity of dactimicin, the first aminoglycoside possessing the N-formimidoyl group, was compared with that of astromicin and, in part, amikacin, ribostamycin, kanamycin and gentamicin as reference aminoglycoside antibiotics. When a dose of 200 mg/kg was given intramuscularly to dehydrated mice, dactimicin caused no change of BUN and serum creatinine, while reference aminoglycosides caused significant elevations of the parameters. In the urinalysis of rats at doses of 40 and 80 mg/kg per day for 11 days or 21 days, dactimicin caused little changes in urinary parameters except for nucleated cells and NAG. In a detailed comparison between dactimicin and astromicin at 20, 40, 80, 120, 180 and 270 mg/kg for 11 or 30 days, dactimicin induced fewer changes in nucleated cells and NAG at high dosages. While dactimicin and astromicin caused no significant changes in BUN and serum creatinine at dosages of 20-270 mg/kg, histological observations using light and electron microscopes revealed that dactimicin consistently showed fewer lesions on the proximal tubular cells than those of astromicin for all dosages. When injected intramuscularly in rats, dactimicin and astromicin showed a similar distribution in the blood and main organs, except for the kidney, in which renal accumulation of dactimicin was about 60% of that of astromicin. Dactimicin slowly degraded in vitro and in vivo to give fortimicin B as a main product which was accumulated in the kidney. Through comparative studies with astromicin, it was disclosed that the N-formimidoyl group of dactimicin did not increase but decreased the nephrotoxicity, probably by suppressing reabsorption of dactimicin via proximal tubular cells.

Topics: Acetylglucosamine; Amikacin; Aminoglycosides; Animals; Anti-Bacterial Agents; Blood Urea Nitrogen; Creatinine; Kidney; Kidney Diseases; L-Lactate Dehydrogenase; Male; Mice; Organ Size; Osmolar Concentration; Proteinuria; Rats; Urodynamics

Dactimicin is a new member of the pseudodisaccharide group of antibiotics. It possesses an unusual N-formimidoyl group which differentiates it from astromicin. Dactimicin is active against wide variety of bacteria, including resistant strains with aminoglycoside-modifying enzymes. However, AAC(3)-I enzyme slowly acetylates dactimicin. Animal toxicity studies show that the ototoxicity and nephrotoxicity of dactimicin are lower than those of amikacin and gentamicin. No notable abnormal findings have been found in pharmacological and toxicological studies.

Topics: Amikacin; Aminoglycosides; Animals; Anti-Bacterial Agents; Bacteria; Drug Resistance, Microbial; Female; Guinea Pigs; Hearing Disorders; Kidney Diseases; Male; Mice; Microbial Sensitivity Tests; Rats

Astromicin (ASTM), a new aminoglycoside antibiotic, was administered to 7 patients with renal disorders. Concentrations of ASTM in blood were determined for pharmacokinetic analysis. ASTM was administered by intravenous drip infusion over 1 hour at a dose of 200 mg to each of 6 patients and at a dose of 100 mg to 1 patient. Renal function was observed by the clearance of intrinsic creatinine (Ccr) as the indicator. Concentrations of ASTM in blood became higher and retention times longer as degrees of the loss of renal function were larger. Although ASTM is proved to be one of drugs with the highest degree of safety compared with other existing aminoglycoside antibiotics, it should be administered with care to patients with renal disorders.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Female; Humans; Infusions, Intravenous; Kidney Diseases; Kinetics; Male; Middle Aged