中国药物警戒 ›› 2026, Vol. 23 ›› Issue (2): 147-154.
DOI: 10.19803/j.1672-8629.20250632

• 基础与临床研究 • 上一篇    下一篇

新利司他杂质A大鼠90 d重复灌胃给药毒性研究

杜建才1, 姚方方1△, 刘若训2, 赵云1, 李国超1, 仇德洋1, 李斌1, 姚景春1,*   

  1. 1鲁南制药集团股份有限公司新药安评中心，中药制药共性技术国家重点实验室，山东 临沂 273499;
    2淄博市中医医院药学部，山东 淄博 255020
  • 收稿日期:2025-09-06 出版日期:2026-02-15 发布日期:2026-02-13
  • 通讯作者: *姚景春，男，硕士，研究员，新药临床前药理毒理学。E-mail: yaojingchun@lunan.com
  • 作者简介:杜建才，女，硕士，助理研究员，药理毒理实验研究。△为并列第一作者。
  • 基金资助:
    山东省自然科学基金资助项目（ZR2022LZY021）

Toxicity of 90-Day Repeated Ingastric Administration of Cetilistat Impurity A in Rats

DU Jiancai1, YAO Fangfang1△, LIU Ruoxun2, ZHAO Yun1, LI Guochao1, QIU Deyang1, LI Bin1, YAO Jingchun1,*   

  1. 1Center for Drug Safety Evaluation of Lunan Pharmaceutical Group Corporation, State Key Laboratory of Common Technology in Traditional Chinese Medicine Manufacturing, Linyi Shandong 273499, China;
    2Pharmacy Department of Zibo Traditional Chinese Medicine Hospital, Zibo Shandong 255020, China
  • Received:2025-09-06 Online:2026-02-15 Published:2026-02-13

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摘要： 目的 探究连续90 d重复灌胃给药新利司他杂质A对SD大鼠出现的潜在毒性反应，为减肥药新利司他的毒副反应研究提供参考。方法 SPF级SD大鼠120只，随机分为4组，即新利司他杂质A 20.0、80.0、320.0 mg·kg-1·d-1 3个剂量组（低剂量组、中剂量组、高剂量组）和溶媒对照组（0.5%羧甲基纤维素钠溶液），每组30只雌雄各半。按照10 mL·kg-1·d-1的给药体积，每日1次，连续给药90 d，停药恢复28 d。试验期间，每天进行一般状态观察，每周1次摄食量测定，2次体重称重。给药期结束和恢复期结束分别进行眼科及尿液检查、血液学检查、血凝检查、血清生化学及电解质检查、骨髓涂片检查、组织病理学检查。结果 新利司他杂质A各剂量组未引起动物一般状态、摄食量、体重、眼科、尿液、血凝指标的异常改变（P>0.05）。中性粒细胞百分比（NEU%）和丙氨酸氨基转移酶、血清总胆红素、总蛋白及尿素值有轻微改变（P<0.05），但数值均在正常范围内，组织病理学检查心脏、肾脏、肝脏、前列腺等个别脏器组织出现轻微病理改变，形态学改变、各组发生例数、病变程度差异均无统计学意义（P>0.05），考虑为动物自发性改变。结论 SD大鼠按照20.0、80.0、320.0 mg·kg-1·d-1剂量连续经口灌胃给药新利司他杂质A未发现明显毒副作用。

关键词: 新利司他杂质A, 新利司他, 灌胃, 重复给药, 毒性, 大鼠

Abstract: Objective To assess the potential toxicity of 90-day consecutive ingastric administration of cetilistat impurity A in SD rats. Methods A total of 120 SPF-grade SD rats were randomly assigned to four groups: the low-dose, medium-dose, and high-dose(20.0, 80.0, and 320.0 mg·kg-1·d-1) treatment groups and a solvent control group that received 0.5% sodium carboxymethyl cellulose solution. There were 30 rats in each group (half male and half female). The volume of administration was 10 mL·kg-1·d-1, once daily and for 90 days, followed by a 28-day recovery period. During the study, health status of these rats was observed daily, food intake was measured weekly, and body weight was recorded twice. At the end of dosing and recovery periods, indexes related to ophthalmology, urine, hematology, coagulation, serum biochemistry, and electrolytes were detected, along with bone marrow smears and histopathological examination. Results No significant changes in health status, food intake, body weight, ophthalmology, urine, or coagulation parameters were observed in any of the dose groups (P>0.05). Minor changes were observed in neutrophil percentages (NEU%) of alanine aminotransferase, total bilirubin, total protein, and urea (P<0.05), but all the values remained within normal limits. Histopathological examination revealed mild pathological changes in such organs as the heart, kidney, liver, and prostate. However, the incidence and severity of these changes were similar across these groups (P>0.05), suggesting that these alterations were likely spontaneous. Conclusion No significant toxic effects are observed in SD rats administered with cetilistat impurity A ingastricly at doses of 20.0, 80.0, and 320.0 mg·kg-1·d-1 for 90 days.

Key words: Cetilistat Impurity A, Cetilistat, Ingastric Administration, Repeated Dosing, Toxicity, Rats

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