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Cephradine, a semisynthetic cephalosporin antibiotic, has a low order of oral and parenteral toxicity in animals. The oral LD,0 in mice and rats ranged from 5 to >8 g/kg, and the intraperitoneal LD50 values in mice and rats were 0.7 to 1.5 g/kg and 4.0 g/kg, respectively. The intravenous LD50 in mice ranged from 3.0 to 3.8 g/kg. In anesthetized dogs, intravenous doses of cephradine (40 and 120 mg/kg, given 45 min apart) had no effect on either the renal or cardiovascular systems. Single intramuscular injections (0.25 ml or 0.5 ml of a solution containing 125 to 235 mg of cephradine/ml) elicited no signs of either pain or local irritation in dogs, and only transient signs of slight-to-moderate irritation were observed in rabbits. In subacute toxicity studies, cephradine was administered for 4 weeks to rats (daily intraperitoneal doses of 160, 480, or 1,600 mg/kg) and dogs (daily intravenous doses of 80, 240, or 800 mg/kg); in addition, over a 2-week period, monkeys were given daily intravenous doses of 60, 180, or 600 mg/kg. No clinical, biochemical, gross, or micropathological changes due to cephradine were observed in these animals; especially notable was the absence of any signs of nephrotoxicity. In chronic toxicity studies, daily doses of cephradine were administered orally to rats (100 to 1,000 mg/kg), dogs (50 to 500 mg/kg), and monkeys (50 to 500 mg/kg) for 26, 26, and 13 weeks, respectively. Significant responses were observed only in rats, in which grossly enlarged, but histologically normal, ceca developed, a common finding in rodents dosed with antibiotics; in addition, there were increases in the relative and absolute weights of the adrenal glands. None of these effects was observed in rats that were necropsied 3 weeks after termination of dosage. In reproduction studies in mice and rats given either daily oral doses (100 or 300 mg/lkg) or daily intraperitoneal doses (rats only; 80 or 320 mg/kg) of cephradine, no drug-related teratogenic changes in the offspring were observed.

Methods have been developed for using the Beckman "Discrete Sample Analyzer" (DSA-560), for automated simultaneous determinations of p-aminohippurate (PAH) and creatinine in the same 50- or 10-µl samples of plasma or urine, respectively, at the rate of 80 samples per hour. In determinations of PAH, a single reagent, p-dimethylaminocinnamaldehyde in 0.1 mol/liter HCl, was added to a protein-free filtrate from plasma or urine. The intensity of the color, measured at 550 nm, obeyed Beer’s law for PAH concentrations from 0.005 to 5.0 g/liter. Data obtained for the same plasma and urine samples by the manual method, were, in general, within ±5% of the results obtained by the automated method. Creatinine was simultaneously determined by adapting the method of Taussky to the DSA-560 instrument; the intensity of the color, measured at 510 nm, obeyed Beer's law for creatinine concentrations ranging from 0.005 to 5.0 g/liter. Data obtained for the same plasma and urine samples by the manual method, were, in general, within ± 5% of the results obtained by the automated method.