[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (5). 6-month repeated dose intravenous toxicity study in dogs with 1-month recovery test].
A 6-month repeated dose toxicity study with 1-month recovery test of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in beagle dogs. The dogs of both sexes were administered ONO-5046.Na intravenously at a daily dose of 0 (vehicle control), 7.5, 15 or 30 mg/kg. In the 15 mg/kg and above groups, transient ataxic gait was observed. It is considered that this symptom could be attributed to the pharmacological effect of ONO-5046.Na. Macro- and microscopic hemorrhage at the injection site was observed in the ONO-5046.Na treated groups. However, it is considered that these findings could be attributed to the long-term repeated dosing procedure, and were not toxic changes. There were no treatment-related changes in body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, electrocardiography and organ weights. These results indicate that the NOAEL of ONO-5046.Na in dogs is 30 mg/kg/day for both sexes in this study.
Okamoto
M
M
Biology and Zoology Research Center Inc., Shizuoka, Japan.
Ide
M
M
Suzuki
H
H
Ishii
T
T
Tamura
K
K
Numata
H
H
Katsumata
T
T
Fujita
T
T
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004431:Ear, External / Q000187:drug effects; D005260:Female; D005684:Gait / Q000187:drug effects; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D007275:Injections, Intravenous; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D013449:Sulfonamides / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors
D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D005998:Glycine