Pharmacokinetic study or PK study is integral to the drug development process. Throughout its various phases, it consists typically of ADME (absorption, distribution, metabolism, and excretion/elimination) studies. PK analysis is critical for drug safety considerations.
The Role Of PK Studies Throughout the Drug Development Journey
Pharmacokinetic study results combine with toxicological data from animal trials. That predicts a safe starting dose for humans. Data from PK analysis in the pre-clinical stage help gather additional safety and efficacy information during later stages.
PK Studies in Phase 1 of Clinical Trial
In phase 1 of clinical drug development, PK analysis helps in determining the safe dosage of the new therapeutic. Pharmacokinetic study results in this phase also reflect the drug exposure effects in special populations such as children, the elderly, etc.
PK Studies in Phases 2 and 3 of Clinical Trial
The main aim of PK studies in phase 2 of clinical trials:
- To understand the effect of the new therapeutic in the patient population as different from normal humans.
- This helps in correlating drug dosage with safety and efficacy.
A range of large studies constitutes phase 3 of clinical trials. The focus is on strengthening the safety and efficacy correlation with dosage. Models get formed on the basis of PK study data of phases 1 and 2 of clinical trials. These models facilitate the choice of dosage ranges
The aim is also to eliminate any possible adverse effects, though such occurrences are rare.
The Importance of Combining Pharmacokinetics with Pharmacodynamics
It is important to capture the interrelationship between pharmacokinetics (PK) and pharmacodynamics (PD). A guidance document published in 2014 emphasizes that.
Collaborative research findings from the reputed Novartis Institutes of Biomedical Research constitute the basis of these guidelines.
Assessing the connection between PK (concentration vs. time) and PD (effect vs. time) in the early phases of research is necessary. That facilitates the effective transition to drug development.
Efficient PK-PD analysis and interpretation help in a more comprehensive understanding of the drug action mechanism.
The benefits of combining of pharmacodynamics and pharmacokinetics in early research:
- Successful identification of additional PK properties.
- Optimization of the compound design.
As per this guidance document, PK-PD modeling can escalate the translation of in vitro compound potency to the in vivo scenario. Effective PK-PD modeling can reduce the number of animal studies needed.
Such modeling also helps the translation of findings from the pre-clinical stage to the clinical trial phases.
Main Principles to Keep in Focus
- There is no need to collect the PK dataset and the PD dataset together. It is important to combine the analysis.
- Formulate the PK-PD hypothesis early in the research stage.
- Refine the initial hypothesis at every stage in the light of the analysis.
- Careful selection of PD biomarkers is necessary when designing PK-PD studies.
- It is important to get PK concentrations and PD readouts from the same animals and samples. Use the same matrix used in the case of satellite animal use.
The drug development process has moved beyond simple PK studies. The practice today is to combine:
- PK-PD analyses
- Population PK (PPK) studies
- Physically-based PK (PBPK) studies, etc.
The advancement, however, has no way diminished the role of PK assays in drug development. They have only become more sophisticated