title: [Toxicity studies of landiolol hydrochloride (ONO-1101) (3). 4-week repeated dose intravenous toxicity study in dogs with 4-week recovery test].
abstract: 4-week repeated dose toxicity study with 4-week recovery test of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in beagle dogs. ONO-1101 was administered intravenously to dogs of both sexes at a dose level of 0 (control), 12.5, 25 or 50 mg/kg/day. No deaths occurred throughout the treatment period. Transitory licking chops, vomiting, nausea, diarrhea and soft feces were observed occasionally in both sexes dosed 25 and 50 mg/kg/day and the incidence seemed dose-dependent. However, those incidence declined in the course of the treatment period. Hematology showed a decrease in red blood cell count, hematocrit and hemoglobin value in both sexes receiving 25 and 50 mg/kg/day. ONO-1101 did not effect on body weight, food consumption, respiratory rate, pulse, rectal temperature, heart rate, blood pressure, electrocardiography, renal or hepatic function, ophthalmology, urinalysis, occult blood in feces, blood chemistry, organ weights, necropsy and microscopic findings at any doses. These results indicate that the no-adverse-effect level of ONO-1101 in dogs is 12.5 mg/kg/day for both sexes in this study.
authors.affiliation: Fukui Institute for Safety Research, Ono Pharmaceutical Co., Ltd., Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Yanagi
authors.forename: Y
authors.initials: Y
authors.lastname: Shichino
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Ueda
authors.forename: H
authors.initials: H
authors.lastname: Oida
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Yonezawa
authors.forename: T
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001769:Blood / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005243:Feces; D005260:Female; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D012007:Rectum / Q000502:physiology; D013997:Time Factors; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D014556:Urine
chemical_list: D000319:Adrenergic beta-Antagonists; D009025:Morpholines; C077049:landiolol; D014508:Urea