[Reproductive and developmental toxicity studies on cefepime dihydrochloride administered subcutaneously to rats during the premating, gestation and lactation periods].

Cefepime dihydrochloride (CFPM) was administered subcutaneously daily at doses of 0, 150, 500 and 1,000 mg/kg for 63 days prior to mating and during mating to male Crj: CD (SD) rats and for 14 days prior to mating and during mating, as well as periods of gestation and lactation to female SD rats. Saline and L-arginine hydrochloride (L-arginine) were used as control articles. Daily doses of test and control articles were equally divided and administered twice a day (b.i.d.). The results obtained are summarized as follows: 1. Soft stool was observed for both male and female F0 rats at CFPM 1,000 mg/kg at the first week of administration period. Further, depilation of injection sites was found in 7 males and 12 females at the same dose level. 2. Body weight gains were suppressed in male F0 rats from Day 28 to 63 of administration period at CFPM 1,000 mg/kg. Moreover, food consumption was reduced in F0 female rats during the first week of administration period at all dose levels of CFPM. 3. CFPM failed to affect the reproductive performance in both male and female F0 rats. 4. Kidney weights were increased in both male and female F0 rats and adrenal weights were augmented in male F0 rats at CFPM 1,000 mg/kg. On the other hand, cecal enlargement were observed for F0 dams treated with CFPM. However, these changes were not considered to be unique to this drug, because they have been described with most antibiotics in this species and appears to be results of modifications in gut flora. 5. Prenatal developments in F1 fetuses were not affected by CFPM. 6. CFPM failed to affect delivery status of F0 dams or survival and lactation indices in F1 pups. 7. CFPM did not affect postnatal differentiations, developmental behaviors, learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 8. Body weight gains and food consumption in both male and female F1 rats were not affected by CFPM. 9. CFPM did not alter the organ weights in both male and female F1 rats. 10. There were no significant differences between drug treated animals and controls regarding the reproductive performance and delivery status of F1 rats. 11. Influences on survival indices, body weights and organ weights were not apparently observed for F2 pups even at CFPM 1,000 mg/kg. Based on the reproductive and developmental indices, the no-effect dose level of CFPM under the present experimental condition was estimated to be 1,000 mg/kg/day against dams (F0) and their offspring (F1).