The pharmacology and toxicology of tobramycin in animals and humans are reviewed. After intramuscular and intravenous administration, tobramycin diffuses throughout most body tissues and tissue fluids. Therapeutic concentrations can be obtained by intravitreal or intradural injections. Dogs tolerate intracisternal doses of 0.2 mg/kg without adverse reaction. The half-life of tobramycin in cochlear fluid of guinea pigs and in renal tissues of rats is significantly longer than the serum half-life in these species and is reflected in the ototoxic and nephrotoxic potential of tobramycin and other aminoglycosides. In man, the serum half-life of tobramycin is 2 hr; renal clearance, apparent volume of distribution, and recovery from urine are similar to those parameters for gentamicin. The serum half-life in neonates in prolonged (4.5-8.7 hr). Concentrations of tobramycin in serum are effectively reduced by hemodialysis, but peritoneal dialysis is less efficient in elimination of the antibiotic. Tobramycin crosses the placenta and is concentrated in the kidney and urine of the fetus.
The safety of cefamandole nafate in laboratory animals was evaluated in six species. The acute toxicity of cefamandole after intravenous or subcutaneous administration was similar to that of cephalothin sodium. The subacute and chronic toxicity of cefamandole was studied in rats and dogs for periods of two weeks to six months at doses of 250--1,000 mg/kg per day in rats and 125--1,500 mg/kg per day in dogs. No evidence of significant systemic toxicity was observed in these studies. There were, however, various degrees of local injury at the injection sites that resulted in slight decreases in hemoglobin, hematocrit, and red blood cell counts in the animals in which injury at the injection site was most severe. Studies of reproduction in rats and mice indicated that cefamandole nafate had no teratogenic effects and no adverse effects on fertility, gestation, or growth of offspring. Comparative studies of nephrotoxicity in rabbits demonstrated that the nephrotoxicity of cefamandole nafate was considerably less than that of cefazolin.
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