PRECLINICAL STUDIES

Definition:
A study to test a drug, a procedure, or another medical treatment in animals.
● The aim of a preclinical study is to collect data in support of the safety of the new
treatment.
● Preclinical studies are required before clinical trials in humans can be started.
● Products may include new medical devices, drugs, gene therapy solutions etc.
● After identifying a compound, it is tested on animals to expose the whole
pharmacological profile.
● Experiments are generally performed on rodents like mice, rats, guinea pigs,
hamsters, rabbits.
● After successful results, experiments are performed on larger animals like cats,
dogs and monkeys.
● As the evaluation progresses unfavourable compounds get rejected at each step.

Objectives:
● Whether a drug will move on to studies in humans.
● Designing phase I clinical trials.
● Help to identify criteria for evaluating safety in humans.
● Detect overt toxicity.
● Identify, describe and characterize hazards.
● Establish dose-response estimation of pharmacology and toxic effects.
● Assess drug distribution to organ systems.
● Identify metabolic, kinetic and elimination pathways.

Types:
1. Short term animal studies(acute): Determine pharmacological actions and
toxicity.
2. Long term animal studies(chronic): Look for potential side effects that may result
from long term use like carcinogenicity.

Steps:
1. Identify a drug target.
2. Develop a bioassay.
3. Screen the drug in the assay.
4. Establish effective and toxic doses.
5. File for approval as an investigational new drug.
Types of studies included:
1. Screening tests: These are simply and rapidly performed tests to indicate the
presence or absence of a particular pharmacodynamic activity. Eg. Analgesic
activity.
2. Tests on isolated organs, bacterial cultures: These are preliminary tests to detect
specific activity. Eg. Anti-bacterial, vasodilator.
3. Tests on animal models of human disease: Animal models used such as kindled
seizures in rats, genetically hypersensitive rats, experiments TB in mouse etc.
4. General observational tests: Drug is injected in tripling doses to small groups of
mice which are observed for hidden effects.
5. Confirmatory tests and analogous activities: Compounds found active are taken
up for detailed study by complex tests and confirm the activity.
6. Mechanism of action: Attempts are made to find out the mechanism of action.
Eg.Whether an anti hypertensive is a ꞵ-blocker/ ACE inhibitor.
7. Systemic pharmacology: The effect on major organ systems are studied
irrespective of the primary action.
8. Quantitative test: The dose-response relationship, maximal effects and
comparative efficacy with existing drugs is carried out.
9. Toxicity test: Acute toxicity-single high doses are given to small groups of animals
that are observed for hidden effects and mortality for 1-3 days. Organ toxicity and
lethal dose calculated.

Importance:
● To determine the toxic dose and pharmacological action.
● To check the kinetic profile of a drug and based on it, select the route of
administration in humans for clinical trials.
● It is the requirement of the regulatory body for performing clinical trials.
● From an ethical viewpoint, it is necessary to check safety of drugs on
animals before starting to check on human beings.