Pharmacokinetic (PK) analysis in clinical trials is critical to understanding the absorption, distribution, metabolism, and excretion profile. Pharmacokinetic studies during clinical trials are conducted in healthy volunteers and/or study patients. These studies are critical for designing and performing subsequent stages of clinical trials. Besides, PK analysis in clinical trials helps evaluate the safety and efficacy data while developing new drug products and their post-marketing evaluations.
Understanding bioavailability is also critical to comprehend the entire ADME profile of a drug product. But what is the bioavailability of a drug? Bioavailability refers to the amount of drug available at the site of action. Notably, toxicological data and nonclinical pharmacological evaluations should be considered while studying clinical pharmacokinetic studies. The current article discusses PK analysis in clinical trials and its role in drug development and regulatory approval.
Pharmacokinetic studies in clinical trials
Clinical pharmacokinetic studies help drug developers determine appropriate applications of a product suitable for patient characteristics such as genotype of enzymes, disease states, and influence on drug-drug interactions. Moreover, pharmacokinetic studies help in therapeutic drug monitoring. Therapeutic drug monitoring is necessary to evaluate individual PK parameters in close relation to adverse drug reactions and drug efficacy in individual study subjects.
Each investigational drug product is unique. It may differ in pharmacological actions, chemical and physical properties, pharmacokinetic and toxicity data, and applications in clinical use. Hence, drug developers should have appropriate development plans while developing new drug products. Besides, regulatory guidelines such as the International Conference on Harmonization and US FDA regulations should be considered while developing advanced drug products such as gene therapy.
During clinical pharmacokinetic studies, scientists should choose appropriate bioanalytical methods depending on the inherent properties of a drug product while considering all existing information from early nonclinical studies. Some drug products may require supplementary testing. These additional requirements help avoid unnecessary testing during the drug development phase.
Analytical methods employed during clinical pharmacokinetic studies should be adequately validated, in terms of precision, accuracy, specificity, and quantitation limits. Besides, adequate stability considerations are necessary while transporting, storing, and analyzing study samples.
PK analysis in clinical trials should employ assay methods that were used from the early stages of drug development. However, analytical methods may differ from early-stage drug development. Hence, drug developers should perform cross-validation to clarify the connection between different assays.
In cases when researchers may not be able to measure or detect drug products and their metabolites in biological samples despite enhanced assay sensitivity, a proper explanation is required. Pharmacokinetics parameters should be adequately estimated through adverse reactions or pharmacologic data for determining PK properties in human tissues and organs.
Early stages of drug development do not usually use a final formulation for pharmacokinetic studies. However, PK analysis in clinical trials requires final formulation before submission of the NDA. Importantly, radioisotope or stable isotope-labeled drug products should not have any deviation in their PK properties due to drug labeling.
In conclusion
pharmacokinetic studies are crucial for understanding ADME properties and supporting drug safety and efficacy data.
