Fertility study of cefodizime sodium in mice--intravenous administration from pre-conceptional period through early period of gestation

Abstract

Cefodizime sodium (THR-221) was intravenously administered to mice of both sexes at dose levels of 300, 1000, 2000 and 3000 mg/kg/day, and its effects on the fertility of male and female mice and on their offspring were examined. Twenty-four males and 24 females were used per dose and as a control group. The males were dosed for 9 weeks prior to mating and through the mating period, and the females were treated from 2 weeks before mating through day 6 of gestation. Cesarean sections were performed on all pregnant mice in each group (16-23) on day 18 of gestation. Of the parental mice, 1, 2 and 1 males died at 0 (control), 2000 and 3000 mg/kg/day, respectively, and 5 females died at 3000 mg/kg/day. Inflammatory changes in the skin at the injection site were observed in the males at 3000 mg/kg/day. In the males, the kidney weight at 3000 mg/kg/day and the spleen weights at 2000 and 3000 mg/kg/day increased, and the thymus weight at 3000 mg/kg/day decreased, as compared with the control values. No differences appeared between any compound-treated group and the control group in the following maternal and fetal parameters: copulation rate, conception rate, and body and placental weights, crown-rump length and sex ratio of the live fetuses. External, visceral and skeletal examinations on the live fetuses revealed no compound-related abnormalities. From the present results, it is considered that the no-effect doses of THR-221 for the parental mice and the fetuses are 1000 and 3000 mg/kg/day, respectively.