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Study of the principles in the first phase of experimental pharmacology: the basic step with assumption hypothesis.
BMC Pharmacology and Toxicology ( IF 2.8 ) Pub Date : 2019-05-21 , DOI: 10.1186/s40360-019-0306-x
Yilkal Tariku Belay 1
Affiliation  

BACKGROUND Experimental pharmacology deals with effects of various test substances studied on different animal species which is aimed at finding out safe therapeutic agent suitable for public health as well as mechanism and site of action of a test substance. It is the basic step in the discovery of new drugs or studying the pharmacological actions of already developed one using both preclinical and clinical study designs in a stepwise phase of investigations. However, the investigations in the first phase of experimental pharmacology are usually concluded with assumption hypothesis without any adequate validation of the scientific evidence. Single dose acute toxicology had been conducted on Balb c mice with three different level of doses prepared from each of three different test chemicals (Dichlorvos, Chlorpyrifos and Cypermethrin) with known median lethal dose (LD50) to define the fundamental principles, cause of toxicity and investigation timeframe in the first phase of experimental pharmacology. METHODS The methods used for data collection were: procurement of test chemicals, investigation of single dose acute toxicity on Balb c mice and quantitative immunoglobulins test. Data was thematically compiled for validation of the findings from each of the sources. RESULTS The result showed that the dose had never limited the toxic property of tested chemicals but the magnitude of adverse effect and length of time at which adverse effect was manifested on treated Balb c mice. The toxicity of tested chemicals was however limited by the toxic reaction rate of a dose in the biological process of exposed Balb c mice. The toxic effect of tested chemicals became magnified within a short period of time when large amount administered orally. It also remained after a long period of time when small amount administered in the same route. CONCLUSION Adequate investigation time for acute toxicity study was therefore essential for comprehensive analysis of pharmacological property of tested chemicals at different level of doses.

中文翻译:

实验药理学第一阶段原理的研究:带有假设假设的基本步骤。

背景技术实验药理学研究了在不同动物物种上研究的各种测试物质的作用,其目的是寻找适合公众健康的安全治疗剂以及测试物质的作用机理和作用部位。这是发现新药或通过分阶段研究的临床前和临床研究设计来研究已经开发的药物的药理作用的基本步骤。但是,在实验药理学第一阶段的研究通常以假设假设为结论,而没有对科学证据进行任何充分的验证。已对Balb c小鼠进行了单剂量急性毒理学研究,小鼠使用三种不同的测试化学品(敌敌畏,毒死rif和氯氰菊酯)具有已知的中值致死剂量(LD50),以定义实验药理学第一阶段的基本原理,毒性原因和研究时间表。方法用于数据收集的方法是:购买测试化学药品,对Balb c小鼠进行单剂量急性毒性调查和定量免疫球蛋白测试。对数据进行了主题汇编,以验证来自每个来源的发现。结果结果表明,该剂量从未限制过所测试化学药品的毒性,而是对治疗的Balb c小鼠产生了不良反应的程度和出现不良反应的时间长短。然而,在暴露的Balb c小鼠的生物学过程中,受试化学药品的毒性受到剂量毒性反应速率的限制。当大量口服时,被测化学品的毒性作用在短时间内被放大。长时间以相同的途径给药后,它也会保留下来。结论因此,充足的急性毒性研究时间对于全面分析不同剂量水平的被测化学品的药理特性至关重要。
更新日期:2019-05-21
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