药物发现与评价：安全性及药代动力学评估

English | PDF (True) | 2013 | 1387 Pages | ISBN : 3642252397 | 27.1 MB

Safety aspects have become an outstanding issue in the process of drug discovery and development. Until 15 years ago safety aspects were addressed by pharmacological testing of the selected compound in high doses in tests directed at indications other than the intended indication of the new compound. These tests were followed by pharmacokinetic studies, which were mainly aimed at confirming of a suitable half-life time and at oral activity. Safety aspects relied mostly on toxicity studies, which however gave information on changes of organ structure rather than on organ function. Toxicological and pharmacokinetic studies were adapted to the progress of studies in clinical pharmacology and clinical trails. But the success rate in the pharmaceutical industry and the introduction of new chemical entities to the market per year dropped dramatically, whereas the development time for a new compound increased, sometimes exceeding the patent protection. A change of strategy was therefore adopted, involving the following changes

- Parallel instead of sequential involvement of the various disciplines (multidimensional compound optimization).

- The term "Safety Pharmacology" was coined. The International Conference on Harmonization (ICH) founded a Safety Pharmacology Working Group. Easily accessible and the most informative tests now have to be selected.

- Exposure of a drug to the body by pharmacokinetic studies on absorption, distribution, metabolism and excretion has to be investigated at an early stage of development and can contribute to the selection of a compound for development.

Toxicology experienced major achievements by the introduction of new methods, e.g., in silico methods, toxicogenomics and toxicoproteomics.

The book is a landmark in the continuously changing world of drugs. As such it is important reading for many groups: not only for all students of pharmacology and toxicology but also for physicians, especially those involved in clinical trials of drugs, and for pharmacists who have to know the safety requirements of drugs.

The book is absolutely essential for scientists and managers in the pharmaceutical industry who are involved in drug finding, drug development and decision making in the development process.

In particular, the book will be of use for government institutions and committees working on official guidelines for drug evaluation worldwide.

安全性方面的问题已成为药物发现和开发过程中一个突出的议题。直到十五年前，安全性问题都是通过对选定化合物在高剂量下的药理学测试来解决，这些测试的目标是治疗不同于新化合物预期用途的症状。接下来进行的是药代动力学研究，其主要目的是确认合适的半衰期时间以及口服活性。安全性方面主要依赖毒性研究，尽管这些研究提供了器官结构变化的信息，但并没有提供器官功能的变化信息。毒理学和药代动力学研究都遵循临床药理学和临床试验的进步。然而，在制药行业中的成功率显著下降，并且每年引入市场的新化学实体的数量也急剧减少，而新化合物的研发周期却延长了，有时甚至超过了专利保护期。因此，采取了一种新的策略，涉及以下改变： - 并行而非序列地参与各种学科（多维度的化合物优化）。 - 创建了一个新的术语“安全性药理学”。国际协调委员会（ICH）成立了一个专门的安全性药理学工作组。现在必须选择最易获得且最有信息性的测试。 - 在药物开发早期，必须研究药物对身体的影响，包括吸收、分布、代谢和排泄的药代动力学研究，这可以有助于化合物的选择进行开发。 毒理学通过引入新的方法取得了重大成就，例如体外的方法、毒物基因组学和毒蛋白组学等。 这本书是不断变化中的药物世界中的一座里程碑。因此，它对于许多团体来说都是重要的读物：不仅是所有药理学和毒理学的学生，而且对临床试验中的医生特别重要，尤其是那些研究药物的医生，以及需要了解药品安全要求的药师。 对于参与药物发现、开发和决策过程的行业科学家和经理来说，这本书是必不可少的。 尤其，这本书将对世界各地负责制定药物评价官方指南的政府机构和委员会有用。

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