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What is toxicokinetics?

Toxicokinetics, referred to as toxicokinetics, is the application of the principles of pharmacokinetics in toxicology.

Apply mathematical methods to study the dynamic process of the amount of foreign compounds or their metabolites changing with time in the body, focusing on the quantitative law of their absorption, distribution, biotransformation and excretion in the body. The analysis steps can be roughly divided into:
1. Propose an appropriate compartment model according to the characteristics of foreign compounds transported in the body;
2. According to the selected compartment model, list the differential equations to solve;
3. Calculate the parameters of the model and their error estimates from the experimental data;
4. Use toxicokinetic data to evaluate the toxicological safety of foreign compounds, or to study the treatment of poisoning and the mechanism of toxicity.

Toxicokinetic test is to use the principles and methods of pharmacokinetics to quantitatively study the absorption, distribution, metabolism, excretion process and characteristics of drugs in animals under toxic doses, and then to explore the law of the occurrence and development of drug toxicity. Understand the distribution of drugs in animals and their target organs.

Research value
For innovative drugs, toxicokinetics research has obvious value in the following aspects:
1. Describe the systemic exposure of the drug in toxicity studies and the relationship between dose and time;
2. Describe the effects of repeated doses of extension of exposure on metabolic processes, including effects on metabolic enzymes (such as induction or inhibition of drug-metabolizing enzymes);
3. Explain the toxicological findings or changes of the drug in the toxicity test. Evaluate the toxicity of drugs in different species, sex, age, physical state such as disease or pregnancy, and support the selection of animal species and drug regimen for non-clinical toxicity studies;
4. Analyze the value of animal toxicity performance in clinical safety evaluation, such as liver toxicity or kidney damage caused by drug accumulation, which can provide information for subsequent safety evaluation;
5. Toxicology tests combined with toxicokinetic studies can provide more sufficient information support for non-clinical studies, such as clinical phase I dose selection, dose exploration tests, toxicity reactions and their severity analysis, etc.;
6. In some cases, a short-term subacute toxicity test (1-3 months) accompanied by a toxicokinetic study can better support the drug’s entry into early clinical trials, help reduce the safety risks of clinical trials, and help shorten the duration of the drug. research period.

To provide the basis for further other toxicity tests, and to provide the basis for the diagnosis and treatment of clinical drug use and drug overdose in the future.