Toxicokinetic Studies Vs. Non-Clinical Toxicology

The drug development process passes through both non-clinical and clinical phases. Non-clinical studies are conducted in animal models employing different protocols. During early drug development, sponsors conduct several studies, including ADME studies for drug availability and preliminary studies, such as toxicology studies, safety, and general efficacy studies. These studies generally do not need GLP compliance as they aim at investigating experimental factors for subsequent clinical decisions.

However, other studies need GLP compliance. These introductory GLP studies include genotoxicity, repeated dose toxicity studies, and safety pharmacology studies. Hence, these investigations form the core component of IND enabling studies. The current article highlights the difference between toxicokinetic studies and non-clinical toxicology studies. Let us focus on toxicokinetic studies first and then move on to non-clinical toxicology.

Toxicokinetic studies

Toxicokinetic (TK) studies are generally conducted along with tox studies. These studies are GLP compliant. The primary aim of TK studies is to measure systemic drug exposure in animals and characterize the relationship between the time course and the administered drug doses. Besides, a well-defined PK profile is always advantageous to determine the toxicological findings in the best possible way.

Generally, regulatory guidelines recommend performing toxicokinetic studies during non-clinical toxicology analysis. Toxicokinetic studies also evaluate the potential of drug accumulation in specific tissues or organs. This assessment is crucial, particularly when interpreting toxicological data from non-clinical and clinical toxicology testing and comparing safety and risk factors in human studies..

Moreover, the fundamental aspects to consider while understanding the relationship between systemic drug exposure and absorbed drug fraction in tissues are:

• Identifying drug absorption
• Evaluating the absorption rate
• Drug distribution in the body
• Drug metabolism
• Identifying target organ, rate of metabolism, and generated metabolites
• Route and rate of drug elimination
• Effect of drug ADME properties.

Let us now focus on non-clinical toxicology studies.

Non-clinical toxicology studies

As new therapeutic approaches require guaranteed safety and efficacy in humans, advances in drug development have become a challenge. Non-clinical toxicology studies aim at assessing the drug compound for its toxic effects in different animal models. Besides animal studies, researchers also employ several in vitro approaches to evaluate the non-clinical toxicology profile of a potential drug candidate. However, in vitro approaches are often complemented with in vivo studies.

Performing non-clinical toxicology in a specific sequence is beneficial for a new drug product. Non-clinical toxicology studies include acute, subchronic, and chronic toxicity analysis, mutagenicity tests, reproductive toxicity, safety pharmacology, carcinogenicity, and local tolerance tests. Although a standardized program is not available for non-clinical toxicology studies, a well-designed program helps avoid potential errors and unnecessary testing

Toxicological tests are crucial for the success of a pharmaceutical drug product. Each drug product is unique and requires specific protocols for regulatory approvals. For example, vaccines generally do not require mutagenicity, reproductive or carcinogenicity tests. On the other hand, each drug product has unique characteristics and is developed for a specific disease or disorder. Hence, each toxicological study must be tailored to a particular developmental program. Besides, a well-designed program is necessary to anticipate potential side effects and can help consider additional specifications for a robust drug development endeavor.