[Fertility study of cefodizime sodium in mice--intravenous administration from pre-conceptional period through early period of gestation].
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.
Akaike
M
M
Pharma Research and Development Division, Hoechst Japan Limited, Saitama.
Kitatani
T
T
Takayama
K
K
Kobayashi
T
T
D000818:Animals; D002439:Cefotaxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005333:Fetus / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013997:Time Factors
D002439:Cefotaxime; C033356:cefodizime