What are the Differences between in vivo and in vitro testing of drugs for toxicology Studies?

In toxicology studies, there are two main types of tests used to assess the safety and potential toxic effects of drugs: in vivo tests and in vitro tests. We know that the traditional method of drug toxicology research is to use animal models for in vivo drug testing. Although this method can fully reflect the various toxic effects of drugs and allow long-term observation of chronic toxic effects, there are many interfering factors and it is difficult to conduct metabolic and mechanistic studies.

With the development of science and technology, the use of free organs, cultured cells, or organelles for toxicological in vitro testing has slowly emerged.

Toxicology is the science of studying the harmful effects of chemical, physical, biological, and other exogenous factors on biological systems. It can study the toxic reactions of chemical substances on living organisms, their severity, frequency of occurrence, and mechanisms of toxic effects, as well as qualitative and quantitative evaluation of toxic effects.

The purpose of toxicological studies in drug discovery is to establish the toxicity information of drugs through animal experiments to predict the possibility of human clinical use to develop preventive and control measures, while projecting the purpose of safe reference doses and safety ranges for clinical studies, including drug in vivo tests and drug in vitro tests.

1.       Differences between in vivo and in vitro drug testing studies

In vivo, drug tests are scientific studies that evaluate the safety and efficacy of drugs in vivo using laboratory animals such as mice, rats, or rabbits.

These tests allow researchers to understand the metabolism, pharmacokinetics, and pharmacokinetic characteristics of drugs in animals, determine the effective dose range and toxic effects, and assess the toxicity and potential adverse effects of drugs in animals at different dose ranges.

In vitro, experimental toxicology studies involve the use of techniques such as in vitro models or cell lines to assess the effects of drugs on human cells or tissues and to study the pharmacodynamic and metabolic kinetic properties of drugs.

These studies can help people better understand the mechanism of action of drugs in the human body and also predict the toxic reactions of drugs, to better protect human health.

2.       In vivo testing for toxicological research

In vivo, testing of drugs using whole animals is the basic method of toxicology research, mostly used to detect the general toxicity of drugs, including acute toxicity, subacute toxicity, subchronic toxicity, and chronic toxicity.

Mammals such as mice, rats, guinea pigs, hamsters, rabbits, dogs, and monkeys are generally used to observe the toxic reactions of drugs.

During the experiments, it is necessary to select suitable animals according to the experimental requirements and to improve the reference value of the experimental results by controlling gender, age, genetic characteristics, etc., to better extrapolate the experimental results to humans and make them closer to the actual clinical drug use.

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Advantages:

ž   They mimic the physiological conditions and complex interactions in living organisms.

ž   They enable researchers to assess the overall systemic effects of drugs.

ž   They provide insight into the metabolism, distribution, and potential toxicity of drugs in various organs.

Since humans are the most sensitive animal species and the biological processes in humans and laboratory animals include the metabolism of chemicals, the effects produced by foreign chemicals in laboratory animals can be extrapolated to humans.

Moreover, exposure of experimental animals to high doses of compounds is a necessary and reliable method to discover potential hazards to humans, and the possible exposure pathways of adult healthy experimental animals and humans are the basic choices.

However, traditional methods of toxicological studies are facing great challenges due to the rapidly growing number of compounds to be tested, the high cost and time-consuming nature of testing, interspecies differences, and animal protection.

Disadvantages:

ž   They are time-consuming, expensive, and require ethical considerations due to the use of animals.

ž   Results obtained from animal studies may not always accurately predict human responses.

ž   The high degree of variability among species may limit the extrapolation of data to humans.

3.       In vitro experiments for toxicological studies

In vitro, experiments are used to observe the harmful effects of drugs and drug metabolism using stereological animal organs, cultured cells, organelles or biomimetic systems, etc. They are mostly used for preliminary screening of acute toxic effects of drugs on the organism, study of mechanisms of toxic effects, and biotransformation processes.

The application of such methods solves the ethical problem of using a large number of experimental animals in the overall animal experiments with the endpoint of animal death or dying on the one hand and increases the controllable factors in the experimental process and enhances the reliability of the experimental results on the other hand.

In vitro, testing is a method to provide toxicological information by maintaining the normal physiological function of a target organ or target cell, or even a target molecule in vitro and observing the effect of the subject on it, which has the advantages of simplicity, speed, economy and direct use of human cells, and is used for toxicological research together with the whole test.

Advantages:

ž   They provide a controlled environment to study specific cellular or molecular mechanisms.

ž   They are relatively faster, more cost-effective, and do not involve the ethical issues associated with animal testing.

ž   They can be used to screen a large number of substances or compounds to identify potential toxic effects.

Disadvantages:

ž   They may not fully represent the complexity of the whole organism and may miss systemic effects.

ž   They cannot account for the metabolism, distribution, and excretion of drugs in the body.

ž   They may not accurately predict the effects of drugs in humans due to differences in cell cultures or tissues compared to actual human physiology.

The advantages of using in vitro drug testing for toxicological studies are that there are few interfering factors, easy to control, and metabolic and mechanistic studies can be conducted.

However, the disadvantage is that it does not provide a comprehensive response to the various toxic effects of drugs, lacks the overall toxicokinetic process, and makes it difficult to study the chronic toxic effects of drugs.

In vivo and in vitro drug tests have their advantages and disadvantages in the study of toxicology, so when conducting metabolic or toxicological studies of exogenous substances, the experimental design should be based on the advantages and disadvantages of in vitro and in vivo tests, weighing the pros and cons.

In conclusion, both in vivo and in vitro toxicological studies are indispensable aspects of the preclinical research process of new drugs, and the combination of the two can comprehensively assess the safety and efficacy of drugs and provide an important reference basis for the development of new drugs.