General Pharmacology Research of New Drugs

What is General Pharmacology Research?

General Pharmacology research refers to the study of extensive pharmacological effects of new drugs other than the main pharmacological effects. It mainly studies the effects of drugs on the spirit, nervous system, cardiovascular system, respiratory system, and other systems.

General Pharmacology Research of New Drugs is divided into three categories, namely Primary Pharmacodynamic, Secondary Pharmacodynamic and Safety Pharmacology. In addition, additional and/or supplementary studies on safety pharmacology (Follow-up and Supplemental Safety Pharmacology Studies) may be required according to experimental requirements. Safety pharmacology is mainly to study the potential undesired adverse effects on physiological functions of drugs at doses within or above the therapeutic range, that is, to observe the effects of drugs on the central nervous system, cardiovascular system, and respiratory system. Additional and/or supplementary safety pharmacology studies may be conducted as needed.

General pharmacology research refers to a wide range of pharmacological research beyond the main pharmacodynamic effects, including the research categories of secondary pharmacodynamics and safety pharmacology. Through general pharmacological research, it is possible to determine the unexpected drug effect of the test substance, which may be related to human safety; evaluate the adverse drug reactions and/or observed in toxicology and/or clinical studies of the test substance Pathophysiological effects; studies of observed and/or presumed mechanisms of adverse drug reactions.

Drug Safety Evaluation

Medicilon has a quality management system for drug safety evaluation based on the internationally certified AAALAC quality standard and compliance with international and domestic GLP regulations.

www.medicilon.com/services/drug-safety-evaluation/

Since 2008, we have continued to meet international standards and completed high-quality GLP safety evaluation services, establishing a long-term brand effect. Medicilon can perform systematic evaluation services covering multiple toxicity endpoints and has internationally recognized pathology studies to support our safety evaluation studies.

Follow-up Safety Pharmacology Studies: Estimate possible adverse reactions based on the pharmacological effects and chemical types of the drug. If there is any doubt about the results of the existing animal and clinical trials, which may affect human safety, additional safety pharmacology research should be carried out, that is, in-depth research on the central nervous system, cardiovascular system and respiratory system.

Supplemental Safety Pharmacology Studies: It is to evaluate the effect of the test drug on the functions of organs other than the central nervous system, cardiovascular system and respiratory system, including the urinary system, autonomic nervous system, gastrointestinal system and Research on other organs and tissues.

Through general pharmacological research, it can provide reference for the design of long-term toxicity test, provide information for clinical research and safe drug use, and provide information for the development of new indications. Experimental animals commonly used mice, rats, dogs and so on. Both in vivo and in vitro systems can be used for general pharmacological research. General pharmacological studies in vivo should try to determine the dose-effect relationship and time-effect relationship of adverse effects; in vitro studies should try to determine the dose-effect relationship of the test substance. General pharmacology focuses on the effects on the central nervous system, cardiovascular system and respiratory system.

History of general pharmacology

In 1968, at the Berlin Pharmacology Conference, Professor Irwin S made an important report on "Comprehensive Testing and Evaluation" - "Procedure for Systematic Quantitative and Quantitative Evaluation of Mouse Behavior and Physiological State", which laid an important foundation for the development of general pharmacology. In 1993, the "Compilation of Guiding Principles for Preclinical Research of New Drugs (Western Medicine)" promulgated by the Ministry of Health of China, for the first time appeared the guiding principles for general pharmacological research of new drugs.

In 1997, ICH (International Conference on Harmonization of Technical Regulations for Registration of Drugs for Human Use) issued the "Guidelines for the Timeline of Non-clinical Safety Research for Clinical Trials of Drugs" (Guidelines M3) and "Preclinical Safety Evaluation of Biotechnology Drugs" " (S6 Guiding Principles) for the first time changed general pharmacology research to safety pharmacology, which raised safety pharmacology to a new stage. Before the concept of safety pharmacology was adopted, the concept of general pharmacology research was widely used.

International Conference on Harmonization of Requirements for Registration Pharmaceuticals for Human Use, referred to as ICH, was co-sponsored by the tripartite drug administration authorities of the European Community, Japan, and the United States and the tripartite pharmaceutical enterprise management agency in 1990 , an international coordination organization that coordinates the existing differences in the technical regulations for the registration of pharmaceuticals for human use in the three countries.

General pharmacological research from the perspective of pharmacology - why do general pharmacology research?

Drugs are applied to the human body and are distributed to various organs and tissues in the body along with the blood circulation. Therefore, before using a new compound, you should have a basic understanding of its overall effect. Only with a basic understanding of its comprehensive pharmacological effects can a correct evaluation of the main pharmacological effects be made. Since the drug acts on the whole, it should have a holistic understanding.

Secondly, general pharmacological research also helps to understand the pharmacological mechanism of new drugs. Where is the site of action of the new drug and what is the mode of action? Only through comprehensive pharmacological observations can we understand. Only through general pharmacological research and analysis of whether the drug acts on the central nervous system, or the heart, ganglion, peripheral blood vessels, and ion channels, can the indications be correctly grasped in clinical application.

General pharmacological research from the perspective of toxicology - why do general pharmacological research?

The toxicity evaluation of new drugs of course depends on various toxicity evaluation methods such as acute toxicity, long-term toxicity, and special toxicity. However, long-term toxicity evaluation is often preceded by acute toxicity and general pharmacology studies. This is because the long-term toxicity test requires a lot of investment, time-consuming and labor-intensive, and therefore has higher requirements for the experimental design. Through general pharmacological research, it is possible to comprehensively survey the main action sites, action properties and action characteristics of drugs, which is an important reference for the experimental design of long-term toxicity tests. Although long-term toxicity tests have basic regulations in terms of indicators, dosage, observation period, route of administration, animal species and quantity, etc., there should be some more targeted designs that combine the characteristics of each drug. Especially the design of special indicators.

In addition to serving as the basis before long-term toxicity tests, general pharmacological research itself is an indispensable supplement to various toxicity tests. Although various toxicity tests such as acute toxicity test, long-term toxicity test and special toxicity test can reflect the toxic effects of drugs from many aspects, after all, there are still many toxic effects that cannot be found by the above-mentioned tests.

The preclinical pharmacological evaluation of new drugs should complete the general pharmacological studies at the same time as the main pharmacodynamic studies. Through general pharmacological studies, the comprehensive pharmacological effects of new drugs can be understood and the drugs can be used to their full potential. At the same time, it is also a preparation for a comprehensive toxicity study, and it is also an important part of a comprehensive toxicity evaluation. Therefore, the current technical requirements for new drug evaluation in various countries regard general pharmacological research as a must-complete project for preclinical pharmacological evaluation of new drugs.