Repeated Dose Toxicity Study

The repeated toxicity test (long-term toxicity test) is the new drug to complete the main pharmacodynamics and acute toxicity test to confirm the other study value of the repeated administration of toxicity test to observe the toxic effects of drugs on animals.

A long-term toxicity test is in a period (the length of time to take the drug according to the clinical application of the decision, generally over one month) by repeated multiple administrations, observation of experimental animals, toxic reactions, hematology, blood Biochemical and pathological changes, analysis of the relationship between the dose of harmful effects, the main target organ, the nature and extent of toxic reactions, the reversibility of poisonous reactions, animal tolerance, non-toxic reaction dose, toxic reaction dose, and safety range; It can also understand the time of toxicity, peak time, duration; whether there is delayed toxicity, whether there is an accumulation of toxicity, tolerance and so on.

Repeated toxicity test is one of the main contents of drug safety evaluation and the primary basis for the transition to clinical trial. It is essential to prescribe the starting dose and safe dose range of the clinical trial, suggesting that the clinical trial focus on monitoring indicators, clinical trial drug poisoning detoxification is of great significance.

Repeated administration toxicity test is the core of non-clinical safety evaluation of drugs; it is acute toxicity, reproductive toxicity and carcinogenicity, and other toxicology research, closely linked to the drug from the pharmaceutical research into clinical trials as an essential part.

In the course of drug development, the purpose of the long-term toxicity test is to characterize the toxic effects of the test substance by repeated administration of the animal test, to predict the possible adverse effects on the human body, and reduce the risk of medication after the use of the clinical trial of subjects.

This test includes the following five aspects:

1. Predict the test substance's possible adverse effects, including the nature of adverse reactions, the degree of dose-response relationship and time-response relationship, reversibility, etc.

2. Determine the repeated administration of the test substance Toxic target organ or target tissue

3. Presumptive clinical trial of the initial dose and repeated drug dose range

4. Prompted clinical trials to need to focus on monitoring indicators

5, Can also be clinical trials of detoxification or rescue measures to provide a reference.

It must be emphasized that the ultimate goal of repeated administration toxicity tests is to serve clinical trials and clinical medication. This principle aims to provide a technical reference for long-term toxicity testing, assist in the technical review of pharmaceuticals, and promote a broader consensus on long-term toxicity testing between drug review agencies and drug registration applicants.

This is a general principle of the long-term toxicity test of chemical drugs, only representing the current basic understanding of long-term toxicity testing, which is only partially the content of the long-term toxicity test that must be completed. The long-term toxicity test of specific drugs should be based on this principle, according to the characteristics of the drug, to develop test programs.