[Cefepime (BMY-28142 diHCl/L-arginine blend): one-month repeated dose subcutaneous toxicity study in rats].

In order to investigate the toxicity of cefepime (CFPM, BMY-28142 diHCl/L-arginine blend upon repeated subcutaneous dosing), the test article was administered to Crj:CD(SD) rats of both sexes at daily dose levels of 150 (low dose), 500 (intermediate dose) and 1,500 (high dose) mg/kg/day by subcutaneous route for 28 days. Two additional groups of rats were given either saline (negative control) or L-arginine (vehicle control). Doses were equally divided and administered twice each day with an interval of approximately 5 hours between the 2 doses of a same day. A half of rats in negative control and high dose groups were retained for examination during one-month recovery period. The results obtained are summarized as follows: 1. Upon general observations, it was found that drug-related changes were restricted to the injection sites. Depilation and scab-formation of the injection sites were noted in high dose rats of both sexes and intermediate dose females. No deaths occurred during the study. 2. Slightly depressed body weight gains were observed for high dose males during the latter part of the dosing period. 3. Slightly lower food consumptions were noted for intermediate and high dose males at Week 1. 4. Slightly higher water consumptions were generally detected for high dose rats during the dosing period. 5. Hematological examinations revealed that a slight decrease in the average value of relative lymphocyte counts and a slight increase in the average value of relative segmented neutrophil counts were evident for high dose males. These findings might be attributable to the inflammatory reactions at the injection sites.(ABSTRACT TRUNCATED AT 250 WORDS)