title: A 4-week oral toxicity study of an antiviral drug combination consisting of arbidol and acetaminophen in rats.
abstract: The antiviral drug combination consisting of arbidol and acetaminophen was investigated for its 4-week repeated oral administration in Sprague-Dawley rats. Groups of rats (10/sex in low-dose group, 15/sex in other three groups) were given at doses of 0, 200, 400, and 800 mg/kg/day. Clinical signs, mortality, body weight, food consumption, hematology, clinical biochemistry, macroscopic findings, organ weights, and histopathology were examined. The administration resulted in increased incidence of piloerection in most of the high-dose females and in some of the high-dose males and mid-dose females. Histopathological examinations revealed minor treatment-related change in the stomach of the high-dose animals. A decrease in body-weight gains and an increase in liver weight were observed in the mid- and high-dose groups. These treatment-related effects were reversible at the 2-week recovery period. A number of other clinical and pathological findings were not considered to be treatment related, since these changes occurred only in one sex were among the normal historical ranges, which were not supported by histopathological findings. Under the conditions of the present study, the no-observed-adverse-effect-level for 4-week oral administration to rats was considered 200 mg/kg/day, based on clinical observations, pathological findings, body-weight losses, and liver-weight changes.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China. mengwang.drug@hotmail.com
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Shu
authors.forename: Wen-Xia
authors.initials: WX
authors.lastname: Bai
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Pan
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Pan
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000633:toxicity*; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000633:toxicity*; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004435:Eating / Q000187:drug effects; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D006651:Histocytochemistry; D007211:Indoles / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides
chemical_list: D000082:Acetaminophen; D018712:Analgesics, Non-Narcotic; D000998:Antiviral Agents; D004338:Drug Combinations; D006454:Hemoglobins; D007211:Indoles; C086979:umifenovir; D013440:Sulfides