Most people are familiar with Clinical trials, which involve Testing the efficacy and safety of a New Chemical Entity (NCE) in human volunteers. However, not many are aware of the process and the huge amount of research involved before a pharmaceutical company gets permission to carry out Clinical trials. These are called Preclinical studies and form an important part of the Drug discovery process.
Drug Discovery:
The process of drug discovery is long and demanding, often stretching up to 15 to 20 years to get a new drug to the patient.
Drug discovery starts, as most things today, in software – or silico so to say. It helps determine the therapeutic target for the particular disease under consideration. Eg. We may need to inhibit or increase the activity of a specific enzyme or receptor or protein in the body so that we get a
therapeutic effect for the disease. In silico software also helps us identify potential molecules that could effectively bind to our therapeutic target. We then move on to the testing part namely preclinical and then the clinical testing phase, which is done in animals and humans,
respectively.
Once we have satisfactory data from this, we progress to the next stage – the in vivo stage. In the in vivo stage, we check the safety, toxicity, activity etc., of the drug inside the body, i.e., in animals, which progresses from smaller animals (rodents) to larger ones (primates), depending on the type of study. The process for the testing of compounds in vivo is set – it starts with pharmacokinetic studies, then pharmacological studies, and finally toxicity studies.
Now let’s discuss the flow of the in vivo testing.
1. Pharmacokinetic studies:
During these studies, we check the pharmacological profile of the drug, specifically, the ADME – Absorption, Distribution, Metabolism and Excretion of the drug. The drug compounds are administered to animals, and we conduct tests for the drug concentrations in blood plasma or tissues to get an idea about the Pharmacokinetic graph or profile.
2. Pharmacodynamic or Pharmacological studies:
In this we develop animal models of a particular disease and test whether the drug is showing any activity against the disease. It also gives us the data on its possible mechanism of action and its interactions with different enzymes, receptors or molecules. Toxicity studies: In these, we evaluate the safety level of the drug and determine the safe doses of the drugs that can be used to achieve the best possible effect of the drug, along with the short-term and long term effects of the drugs.
Why are these studies important?
The data that can be mined from these studies is massively helpful and includes possible dosage form, route of administration, dosage regimen, toxic and safe dose, possible mechanism of action, risks, side effects, tand oxicity. It is also an integral part of the drug discovery process, and data is required for further regulatory approval.
They play an important role in several processes, like:
- Ensuring safety for human volunteers taking part in clinical trials
- Predicting drug interactions
- Identifying dose levels
- Developing tentative dosing regimen
- Identifying bioavailability
- Identifying toxicity levels
So, in conclusion, we may summarize that Preclinical studies are an important step in drug discovery prior to human trials, with great potential for generating data related to new drug compounds, its activity, safety, efficacy, etc., besides being a mandatory step for proceeding with the regulatory drug approval framework.
Ms. Shubhangi Deshpande
Faculty Member at AISSMSCOP and has prior Industry experience as a Research Assistant in the Preclinical testing of Drugs.