Vol.55 No.S-1 October 2007
Reproductive and developmental toxicity studies of garenoxacin
1)Research Laboratories, Toyama Chemical Co., Ltd., 2-4-1 Shimookui, Toyama, Japan
2)Safety Research Institute for Chemical Compounds Co., Ltd.
Abstract
Reproductive and developmental toxicity studies of garenoxacin mesilate hydrate(GRNX) were conducted in Sprague-Dawley rats and New Zealand White rabbits.
In the oral study of fertility and early embryonic development to implantation in rats, suppressed body weight gain and decreased food consumption in males in the 100 and 400 mg/kg groups, and suppressed body weight gain in females in the 1,000 mg/kg group were noted. No effects of GRNX were noted in reproductive ability, sperm examination, estrous cycle, or intrauterine condition on Day 15 of gestation.
In the oral study of pre- and postnatal development, including maternal function in rats, suppressed body weight gain and decreased food consumption were noted during gestation period in dams in the 250 and 1,000 mg/kg groups. No effects of GRNX were noted in reproductive ability of dams, which were indicated by maintenance of pregnancy, delivery or nursing. In offspring, no effects of GRNX were noted in viability, body weight changes, general sign, postnatal development, reflex response, open field performance, learning ability, reproductive ability, or intrauterine condition on Day 20 of gestation.
In the oral study of embryo-fetal development in rats, suppressed body weight gain and decreased food consumption were noted in dams in the 1,000 mg/kg group. No effects of GRNX were noted in reproductive ability of dams, which were indicated by maintenance of pregnancy or findings of caesarean section at term. In fetuses, no effects of GRNX were noted in the number of live, dead and resorbed fetuses, body weights, sex ratio, or external, visceral and skeletal examination. GRNX was concluded to be not teratogenic in rats.
In the intravenous study of embryo-fetal development in rabbits, suppressed body weight gain and decreased food consumption were noted in dams in the 6.25, 12.5 and 25 mg/kg groups, with abortion occurring for 1 to 3 dams. In the 12.5 mg/kg group, death after abortion was observed for 1 dam. In fetuses, decreased body weight of live fetuses and increased incidence with thymic remnant in the neck were observed. These changes were considered to be an effect of delayed growth of fetuses due to the lower body weight of dams, and it could therefore be concluded that GRNX was not teratogenic in rabbits.
Key word
garenoxacin, des-fluoro(6)-quinolone, reproductive and developmental toxicity study, rats and rabbits
Received
May 15, 2007
Accepted
August 22, 2007
Jpn. J. Chemother. 55 (S-1): 62-74, 2007
