Subchronic toxicity and toxicokinetics of LZB, a new proton pump inhibitor, after 13-week repeated oral administration in dogs
文献类型：期刊论文
| 作者 | Mao, Yu2; Zhang, Xiaodong2; Li, Li1; Yuan, Bojun2; Lu, Guocal2 |
| 刊名 | REGULATORY TOXICOLOGY AND PHARMACOLOGY
 |
| 出版日期 | 2008-02 |
| 卷号 | 50期号:1页码:75-86 |
| 关键词 | LZB subchronic toxicity toxicokinetics 13-week oral administration beagle dogs |
| ISSN号 | 0273-2300 |
| DOI | 10.1016/j.yrtph.2007.10.006 |
| 文献子类 | Article |
| 英文摘要 | The subchronic toxicity and toxicokinetics of a novel proton pump inhibitor, pymeprazole (LZB), were investigated in beagle dogs by daily oral administration for 13 consecutive weeks. Three test groups received doses of 30, 100 and 300 mg/kg/day of LZB. Rabeprazole of 60 mg/kg/day was used as positive control. The 13-week repeated oral doses of LZB resulted in objective signs of mild gastrointestinal disturbance for high-close group animals. One individual dog of high-dose group was found to be lethargy and astasia at the last month of administration; for hematology, mild anemia was observed at high-dose females; for clinical chemistry, higher cholest, trigly and gastrin were observed at high-dose females, higher ASAT, ALAT, cholesterol, triglyceride and gastrin at high-dose males were also observed; for histopathology, the primary effects of LZB were related to gastric mucosa of high-dose group seen by H and E or Grimelius stain. Impairment of surface epithelium was observed by SEM. The treat-related effects basically were reversible for a 4-week drug-free period. As for positive control group, 13-week oral administration of rabeprazole resulted in more severe toxicity than high-dose group of LZB although much lower dose was employed. The accumulation of LZB after 13-week oral administration was not notable at the toxic dose of 300 mg/kg/day. The toxic dose was considered to be 100 mg/kg/day and the no-observed-adverse-effect level (NOAEL) to be 30 mg/kg/day, which is much higher than other PPIs. The toxicological target could be stomach, liver, hematological system and nervous system. (c) 2007 Elsevier Inc. All rights reserved. |
| WOS关键词 | ACID-RELATED DISORDERS ; OMEPRAZOLE ; SECRETION ; SAFETY ; PANTOPRAZOLE ; RATS |
| WOS研究方向 | Legal Medicine ; Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000252632800007 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273001]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Yuan, Bojun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Metab Pharmacokinet, Shanghai 201203, Peoples R China 2.Mil Med Univ 2, Ctr Evaluat Drug Safety, Shanghai 200433, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Mao, Yu,Zhang, Xiaodong,Li, Li,et al. Subchronic toxicity and toxicokinetics of LZB, a new proton pump inhibitor, after 13-week repeated oral administration in dogs[J]. REGULATORY TOXICOLOGY AND PHARMACOLOGY,2008,50(1):75-86. |
| APA | Mao, Yu,Zhang, Xiaodong,Li, Li,Yuan, Bojun,&Lu, Guocal.(2008).Subchronic toxicity and toxicokinetics of LZB, a new proton pump inhibitor, after 13-week repeated oral administration in dogs.REGULATORY TOXICOLOGY AND PHARMACOLOGY,50(1),75-86. |
| MLA | Mao, Yu,et al."Subchronic toxicity and toxicokinetics of LZB, a new proton pump inhibitor, after 13-week repeated oral administration in dogs".REGULATORY TOXICOLOGY AND PHARMACOLOGY 50.1(2008):75-86. |
入库方式： OAI收割
来源：上海药物研究所
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