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Role of Toxicokinetic Study in Drug Development and Testing

by Soft2share.com

Have you ever come across a situation wherein your body responds differently to a drug? Toxicokinetics or toxicology is a branch of the pharmacology which is involved in describing the effects and behavior of drug substance and/or drug formulations. Under normal concentration, the drug products are absorbed, metabolized, and eliminated from the body. This depends on what affinity they display for different enzymes, receptors, and transporters. On the contrary, at higher drug concentrations, these enzymes, receptors, and transporters become saturated. This is the reason why your drug behaves and effects you differently.

These days, tk studies are of paramount importance for evaluating systemic exposure of the toxic species to a drug under analysis. The results obtained are then compared with the standard toxicological findings and dose levels. This is based on a generalized assumption that this kind of drug exposure leads to target organ toxicity.

The toxicokinetic study evaluates the ADME (Absorption, Distribution, Metabolism, and Excretion) mechanisms of a drug under analysis.

Overview of the Toxicokinetic Studies –

Here’s a list of the general principles to be considered by every study co-ordinator –

Quantification of Exposure –

This gives the researcher a chance to assess the overall burden on the targeted species.

It makes it easier for the analyst to establish similarities and differentiation between toxicity levels across species.

The setting of dose level (Low, Intermediate, High) –

Pharmacodynamic responses and toxicology findings contribute largely for setting an optimum dose level to perform toxicity studies.

The extent of Exposure Assessment in Toxicity Studies –

It is a pre-requisite of the clinical trials to evaluate the appropriate figure of the animals under analysis as well as that of the dose group. This analysis serves as a base for the risk assessment.

Complication factors in Exposure Interpretation –

Here are complication factors you may come across –

  • A sudden decrease in the systemic exposure on account of protein binding and tissue uptake.
  • Metabolism of the drug product may give rise to pharmacologically active metabolites, antigenic biotechnology metabolites, and toxic metabolites.
  • Factors to be considered for the tk studies are metabolic profile, protein binding, receptor properties, and tissue uptake.

Route of Administration –

Route of administration analysis is critically important both for pharmacokinetic and toxicology studies.

In case, the route of administration is oral, it becomes the responsibility of the clinical technician to check for the oral toxicity.

Determination of Metabolites –

Some situations when the metabolite determination becomes a crucial aspect for toxicokinetic studies –

If your metabolite is a pro-drug and acts as a primary active entity.

In case, the compound undergoes metabolism to form either toxicologically or pharmacologically active metabolites.

 If your drug under analysis is extensively metabolized.

Statistical Evaluation of Data

Statistical evaluation of data must be done to assess drug exposure.

Analytical Evaluation –

Regulatory authorities require the analytical methods should be used for the determination of the blood plasma concentrations of the investigational drug. These analytical testing protocols should be in alignment with the glp toxicological studies of FDA. Frequently employed analytical testing protocols are GC (Gas Chromatography), HPLC (High-Performance Liquid Chromatography), LC-MS (Liquid Chromatography-Mass Spectrometry), Capillary Electrophoresis, and so on.

Reporting –

Food and Drug Administration authorities of any nation where the drug is intended to be marketed requires a thorough documentation system.

Thus, the toxicokinetic study is a scientific discipline that overlaps with the other scientific branches such as biology, chemistry, etc. for studying the adverse effects and behavior of the investigational drug.

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