[Reproductive and developmental toxicity studies of landiolol hydrochloride (ONO-1101) (3). Teratogenicity study in rabbits].
A teratogenicity study of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in KAR:NZW rabbits. ONO-1101 was administered intravenously at a dose level of 0 (control), 25, 50 or 100 mg/kg/day to pregnant rabbit from day 6 to 18 of gestation to examine the effects on dams and fetuses. Death occurred on 3 animals in the 100 mg/kg/day group and one animal in the 50 mg/kg/day group during the treatment period. Hypoactivity, bradypnea/apnea and clonic convulsion after administration was observed in animal dosed 100 mg/kg/day. No maternal effects were seen on body weight, food consumption, necropsy findings or organ weights. External, skeletal and visceral findings revealed no adverse effects of ONO-1101 on fetuses. From the above results, it is estimated that the no-toxic dose level of ONO-1101 under these experimental conditions is 25 mg/kg/day for dams and 100 mg/kg for fetuses.
Nishimura
T
T
Fukui Institute for Safety Research, Ono Pharmaceutical Co., Ltd., Japan.
Chihara
N
N
Sakamoto
T
T
Nakagawa
Y
Y
Aze
Y
Y
Tanaka
M
M
Shimouchi
K
K
Ozeki
Y
Y
Fujita
T
T
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007275:Injections, Intravenous; D008431:Maternal-Fetal Exchange; D009025:Morpholines / Q000008:administration & dosage / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011817:Rabbits; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity
D000319:Adrenergic beta-Antagonists; D009025:Morpholines; C077049:landiolol; D014508:Urea