ADME is an abbreviation for Absorption, Distribution, Metabolism, and Excretion. It represents the drug's disposal process after the drug enters the body. These four properties of the drug determine the concentration, tissue distribution, and metabolic pathways of a drug in the body. It has a very important reference value of predicting the bio-availability and biological activity of the drug (ie, whether a drug can reach its target and produce the appropriate therapeutic effect). Therefore, knowing the ADME properties of a compound is of great importance to the drug development process.
Drug development is a high-risk, high-input, but also a high return process. In this process, the earlier the drug ADME characteristics are evaluated and optimized, the less the ADME characteristics are eliminated in time, which greatly reduces the waste of unnecessary input and resources in the later period. The ADME testing services mainly include high-throughput ADME screening, in vitro drug metabolism testing, drug permeability and transport experiments.
High-throughput ADME screening
As a powerful tool for early drug screening, high-throughput technology has been widely used in the discovery and optimization of lead compounds, making it possible to quickly and efficiently screen large quantities of compounds. The ADME screening process mainly includes the following five steps:
- To be screened for drug screening
- MS/MS method optimization
- ADME detection and sample removal
- LC-MS/MS raw data collection and processing
- Archive of analyzed data
In vitro drug metabolism testing
The safety and effectiveness of drugs are the two most important aspects of the drug development process, and both of these are largely influenced by the interaction between drug metabolism pathways and drugs. Since the drug is normally metabolized into one or more metabolites with increased or decreased activity after entering the body, the metabolic rate of the drug, the biological activity of the metabolites, and the elimination process will directly affect the survival time of the drug in the active form in the body, which affects the plasma concentration and may cause toxic reactions. In addition, the interactions between drugs and drug-metabolizing enzymes also affect the metabolic rates of other drugs and their persistence in the body. Therefore, understanding the metabolic pathways of drugs is very important for better prediction of drug toxicity or side effects and interactions between drugs. At the same time, this information can also provide some guidance for the formulation of dosing regimens, including combined medications.
The main purposes of drug metabolism testing include:
- Identify the main metabolic pathways of drugs and their metabolic enzymes
- Assess the effect of the test drug on the metabolism of other drugs
Drug permeability and transport experiments
The ability of drugs to pass through biofilms is an important factor affecting the absorption of drugs into the blood stream through the digestive tract mucosa and into the various tissues and organs through the bloodstream. Poor drug permeability can result in poor absorption of the drug or affect its distribution in the body. The penetrating ability of drugs is mainly affected by passive diffusion and active transport.
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