Pharmacokinetic (PK) assays have importance in drug discovery and development processes. PK bioanalysis helps researchers identify new drug products, assess their benefits and toxic effects, and guide the design of subsequent clinical trials. However, it is crucial to characterize and validate PK assays for reliable and accurate results. Besides, PK clinical and nonclinical trials must strictly adhere to FDA drug development process guidelines.
The current article gives insight into PK studies in clinical and nonclinical trials.
PK testing in the preclinical setting
PK assays evaluate the absorption, distribution, metabolism, and excretion of a drug product through an organism. Assessing PK properties help sponsors investigate the safety and efficacy profiles of drug products and identify appropriate drug doses for nonclinical and clinical studies. Early preclinical studies involve assessing PK properties in different animal models. These models include non-human primates, rodents, and other animal species. Such non-human studies ensure that a safe and effective dosage is discovered before human studies.
Once early preclinical studies are completed, sponsors focus on lead compound optimization and identification studies. At this stage, a specific number of identified compounds are subjected to preclinical development and toxicological analysis. Such studies may alter the PK properties of the drug candidates. Hence, these modified compounds must be tested for any differences in PK properties.
Moreover, further investigations such as gender differences, fed states, and drug accumulation studies are necessary for comparing single vs. multiple dose PK studies. Higher doses may require added approaches to determine the safe dose levels. Furthermore, in the case of different animal models, PK data is extrapolated from each model and compared to identify critical data points.
Pharmacokinetic clinical trials
Based on the PK results from early preclinical studies, researchers can then design PK testing in clinical trials. In the initial stage, participants are subjected to a single ascending dose (SAD) clinical trial. This initial section ensures that drug effects and safety are monitored at a predefined single drug dose. Only after assessing the drug effects through SAD studies, researchers then move on to multiple ascending doses (MAD) clinical trials for studying steady-state exposures.
During the early clinical trial phase, a small population of healthy volunteers is selected to estimate the initial PK parameters before scaling them to efficacious levels. Such studies involve the assessment of PK parameters before and after the administration of the drug candidate. This measure ensures that adverse events are limited or suspended before escalating the drug doses.
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However, sometime, such as cancer therapeutic, the drug may be initially tested in the disease population. This approach avoids the potential risk in healthy subjects. Not to mention, this process requires clearance from regulatory authorities.
For generic drug products, bioequivalence studies are needed to demonstrate equivalence between the drug candidate and a reference-listed drug. Here, bioequivalence is demonstrated by comparing PK parameters such as bioavailability, Cmax, and AUC.
In Conclusion
PK studies are crucial for the success of a drug development project. They form the basis for demonstrating the safety and efficacy of a novel drug product.
