REPRODUCTION OF RATS UNDER 6315-S (FLOMOXEF)

(2) INTRAVENOUS ADMINISTRATION DURING FETAL ORGANOGENESIS

Abstract

The effects of 6315-S (flomoxef), on Sprague Dawley dams, fetuses and pups were compared with those of cefazolin sodium (CEZ). The 25%(W/V) solutions of the antibiotics were given i. v. once daily for 11 consecutive days beginning on day 7 of pregnancy at doses of 0 (saline, control), 800, 1, 600 and 3, 200 mg/kg/day of 6315-S, or 800 mg/kg/day of CEZ. About 2/3 of the pregnant rats in each group were autopsied on day 21 of pregnancy to examine viability, intrauterine growth and anomalies of fetuses. Skeletal examinations were done on half of le fetuses in each litter after staining with alizarin red-S. Visceral examinations were carried out on the remaining fetuses in each litter by Wilson's freehand section method. Twelve pregnant rats in each group were allowed to deliver and nurse their pups. The pups were examined for viability, growth, development, reflex functions, skeletal system (soft X-ray), behavior (water T-maze and open-field tests), puberty (vaginal opening and penile type), and reproductive performance.
Neither adverse effects on fetal viability nor teratogenic potential were observed in fetuses of the 6315-S groups. Since no dose-related but significant retardation of intrauterine growth of fetuses was found in the 6315-S groups, a supplemental study was done by treatment with low doses of 6315-S. The results showed that the maximum no-effect dose of 6315-S for the intrauterine growth of fetuses was 200 mg/kg/day. Gestation period, parturition and nursing behavior of the mother rats given 6315-S were normal. Body weight gain of newborn pups was suppressed in 6315-S groups in the 1st week, and the suppression continued till about the 10th week in male pups of the 3, 200 mg/kg-treated group. However, the viability, development, reflex and behavioral parameters, sexual maturation, and reproductive performance of the pups born from the 6315-S treated mothers were all normal, suggesting that the suppression of body weight gain in the 6315-S groups exerted no adverse effects on any of the parameters examined. There was no essential difference in the effects attributable to the different treatments in groups given equivalent doses of 6315-S and CEZ.