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What is pharmacodynamics?
What is pharmacodynamics? In a drug discovery experiment, it is necessary to accurately know the possibility of a molecule causing harm to organisms. Understanding the behavior of the drug substance under study in the body will provide a basis for the design of clinical trials and provide valuable data for the launch of new drugs on the market. One of the research areas that can help inform drug discovery and design information is pharmacodynamics.
But what is pharmacodynamics? This article will give a brief overview of this topic and how it is used in drug discovery preclinical trials. It will also briefly introduce the current research on increasing the scalability of PK/PD (pharmaco-kineties, PK pharmacodynamics/(pharmacodynamics, PD drug efficacy) models commonly used in preclinical research.
Overview of Pharmacodynamics
Pharmacodynamics (PD) and pharmacokinetics (PK) constitute the two main branches of pharmacology. Pharmacology studies the biological and physiological effects of drugs on organisms, while pharmacokinetics study how the objects affect drugs. Pharmacology and pharmacokinetics are usually combined in PK/PD test models, which are widely used in preclinical trials.
Pharmacodynamics and pharmacokinetics share common influencing factors, such as dosage, drug benefits, and adverse reactions. Pharmacodynamics particularly emphasizes the response relationship corresponding to the dose, that is, the relationship between the drug concentration and the corresponding biological impact (whether negative or positive).
Negative/adverse effects include increased likelihood of cell mutations (also known as carcinogenic activity), induced physiological damage, abnormal chronic diseases, adverse reproductive effects, and lethality. Therefore, the understanding of drug behavior is absolutely crucial in drug development research.
Recently, the concept of pharmacodynamics has been extended to include multicellular pharmacodynamics (MCPD). The MCPD concept can help researchers understand the dynamic and static relationship between drugs and multicellular three-dimensional tissues in organisms. In this way, the effects of drugs on the smallest multicellular system can be studied in vivo and on a computer.
Networked multicellular pharmacodynamics extends the MCPD concept to include precise modeling of regulatory genomic networks that incorporate signal transduction pathways. Using these concepts, you can more effectively study the complex interacting components in cells and how drugs affect them.
Why is it important to apply pharmacodynamic models in preclinical trials?
As mentioned above, the adverse effects of drugs on organisms may be diverse. It is necessary to ensure that the voluntary nature of drug trials and researchers is that the drugs in drug development will not cause unknown side effects and can be used safely. Therefore, it is very important to accurately clarify the effects of substances on the human body in preclinical research.
Pre-clinical trials need to follow certain regulatory procedures to allow drugs to enter human test subjects. Most experiments include two animal models, one is a rodent and the other is a non-rodent. The pharmacodynamic and pharmacokinetic model of drug action provides specific parameters, which are then used to inform the initial dose in relevant clinical trials.
Expansion of pharmacodynamics from preclinical animal research to humans
One problem of current pharmacodynamic modeling is the scalability of data from preclinical animal studies to human studies, and how to accurately predict the behavior of drugs in humans.
Integrating information obtained from in vitro bioassays and preclinical pharmacology studies in animals can help scientists predict any clinical and adverse effects of drugs. The PK/PD model has several important drug and system-specific factors, including the time course and intensity of the drug’s pharmacological effects.
In bioanalysis, evolutionary omics and computer software have been improved driven by pharmacodynamics. In the past 50 years, the possibility of comprehensive evaluation of the molecular to systemic pharmacodynamics of various drugs has increased. The contemporary PK PD model is constantly evolving.
Due to the fact that this development and model attempt to simulate system-level characteristics, there are many opportunities to expand the pharmacodynamic data. Further improvement of translation PK/PD modeling should improve the efficiency of key drug discovery and development steps.
Recent studies have explored the ability of pharmacodynamics to increase scalability. The review conducted by the team led by Donald E Mager emphasized the basic principles of pharmacodynamics and the basic expectations of PK/PD modeling.
The review also includes a case study on the PK/PD modeling work of recombinant human erythropoietin. This case study is used to demonstrate the potential of pharmacodynamics and can improve people’s understanding of the differences in drug response between species.
Thanks to such studies, it is now possible to extrapolate in vitro, computer simulations and preclinical animal studies to predict the pharmacodynamic properties of drugs in humans.
Preclinical animal studies use pharmacodynamics and pharmacokinetics to predict the behavior of drugs in humans. The use of the PK/PD model can inform parameters such as the dose administered and the potential side effects of the drug used.
With the latest advances in pharmacodynamic modeling, including the increasing scalability of collected data, scientists hope to better understand the behavior of drugs in the human body. This will help future researchers develop safer drugs to put on the market.
(source:internet, reference only)