In drug discovery trials, it is necessary to accurately know the possibility that molecules can cause harm to organisms. After understanding the behavior of the drug substance under study in the body, it will provide a basis for the design of clinical trials and valuable data for the launch of new drugs to the market. One of the research fields that can help inform about drug discovery and design information is pharmacodynamics.
But what is pharmacodynamics? This article will briefly summarize this topic and its application in preclinical trials of drug discovery. The current research on increasing the scalability of the PK/PD (pharmaco-kineties, PK pharmacodynamics /(pharmacodynamics, PD drug efficacy) model commonly used in preclinical research will also be briefly introduced.
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 studies how organisms affect drugs. Pharmacology and pharmacokinetics are usually combined in PK/PD trial 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 dose-corresponding response relationship, that is, the relationship between the drug concentration and its corresponding biological effect (whether negative or positive).
Negative/adverse effects include increasing the possibility of cell mutations (also known as carcinogenic activity), inducing physiological damage, abnormal chronic diseases, adverse reproductive effects and lethality. Therefore, understanding drug behavior is absolutely crucial in drug development research.
Multicellular pharmacodynamics
The concept of pharmacodynamics has been expanded to include multi-cell pharmacodynamics (MCPD). The concept of MCPD can help researchers understand the dynamic and static relationships between drugs and multicellular three-dimensional tissues in organisms. In this way, the effects of drugs on small multicellular systems can be studied in vivo and on computers.
Networked multicellular pharmacodynamics expands the concept of MCPD to include the precise modeling of regulatory genomic networks combined with signal transduction pathways. By using these concepts, it is possible to study the complex interacting components within cells and how drugs affect them more effectively.
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 the voluntariness of drug trials and researchers that the drugs in drug development do not cause unknown side effects and can be used safely. Therefore, it is of vital importance to accurately clarify the effects of substances on the human body in preclinical research.
Preclinical trials need to follow certain regulatory procedures in order for drugs to enter human test subjects. Most experiments involve two animal models, one is a rodent and the other is a non-rodent. The pharmacokinetic and pharmacokinetic models of drug action provide specific parameters, which are then used in relevant clinical trials to inform the initial dose.
Expand pharmacodynamics from preclinical animal studies to humans
One of the current problems in pharmacodynamic modeling is the data scalability from preclinical animal studies to human studies, and how to accurately predict the behavior of drugs in the human body.
Integrating the information obtained from in vitro bioassances and preclinical pharmacological 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 duration and intensity of the pharmacological effects of the drugs.
In bioanalysis, evolution omics and computer software have been improved driven by pharmacodynamics. Over the past 50 years, the possibility of conducting a comprehensive assessment of the molecular-to-systemic pharmacodynamics of various drugs has been increasing. 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 pharmacodynamic data. The further improvement of PK/PD modeling should enhance 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 fundamental expectations of PK/PD modeling.
This evaluation 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 enhance people's understanding of the differences among species in drug responses.
Thanks to such research, it is now possible to extrapolate in vitro, computer simulation and preclinical animal studies to predict the pharmacodynamic properties of drugs in the human body.
