The primary objective of pharmacokinetics (PK) in new drug discovery studies is to understand the absorption, distribution, metabolism, and excretion characteristics of a lead compound and attain a concentration-time profile that fulfills all the safety and efficacy profiles. Besides, understanding the PK properties of drug candidates also involves early pharmacokinetic and pharmacodynamic assessments and linking them to in vitro and in vivo efficacy studies.
Thus, PK assays help researchers improve the generation, optimization, selection, and profiling of potential leads and understand the relationship between pharmacokinetic exposure and pharmacodynamic efficacy. Moreover, once robust PK data are generated in animal models, researchers use these data to correlate and anticipate pharmacological responses in human subjects. Hence, a robust PK analysis can be an effective de-risking approach to reduce the uncertainties and increase the success probability of preclinical and clinical studies.
The current article talks about the approaches drug developers use in PK ELISA assay. In general, four types of ELISA assays are available for PK analysis. However, only one, the anti-idiotypic antibody assay, is widely used in PK analysis. Therefore, the anti-idiotypic antibody bridging ELISA assay is the focus of the current article.
PK ELISA assay for new drug discovery
Bridging ELISA assay is a particular sandwich ELISA method used to study the PK properties of a drug product. This immunoassay method detects an oligomeric or dimeric antigen using capture and detection antibodies. The target antigen bridges the two antibodies, and thus the name bridging ELISA. Bridging ELISA is widely used to assess IgG in anti-drug antibody and PK assays.
In PK ELISA assays, the two antigen-binding sites allow the bridging of an antibody immobilized on the microplate surface and another enzyme-labeled detection antibody. The detection antibody is immobilized on the assay plate and incubated with an antigen solution. After the washing step, the secondary enzyme-labeled antibody is added to complete the bridge. Such bridging assays have several advantages in PK analysis. Some benefits are:
- Antibodies are detected irrespective of their origin or isotype
- Fewer amplification steps lead to reduced background readings
- Two bridging events lead to enhanced assay specificity.
Mostly anti-idiotypic antibodies are produced against antibody drugs, and hence they are usually employed in PK analysis. PK focuses on drug metabolism in a living organism. Thus, researchers assess drug absorption, distribution, metabolism, and excretion in study subjects. To better accomplish these factors, scientists must track bound and unbound antibody drugs at distinct time points. For this purpose, scientists employ anti-idiotypic antibodies to assess antibody drugs in several biological matrices, including serum, plasma, urine, and other fluids. Other than anti-idiotypic assays, there are three different PK ELISA assay types. These include antigen capture assays, anti-idiotypic capture sandwich assays, and anti-idiotypic antigen-bridging assays. However, anti-idiotypic bridging assays are widely used to assess PK properties in the drug discovery life cycle.
Conclusion
Although understanding and translating PK data into clinical readouts is something scientists aim at in the near future, PK ELISA assays are still beneficial in discovering and selecting high-quality drug products and empowering clinical proof-of-concept studies.
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