Pharmacokinetic (PK) testing studies the effects a body has on the administered drug product. Generally, PK assays are evaluated using biological samples such as plasma, serum, blood, and urine. PK testing also includes assessing rare matrices such as CSF and bronchoalveolar lavage fluid. However, regardless of the sample matrix, the drug concentration measured in PK analysis corresponds to the drug concentration available at the site of action. Besides, PK studies also involve measuring excreted drugs through urine. These data points are proportional to plasma drug concentrations.
The pharmacokinetic analysis provides a series of measured drug concentrations over a specific period giving a peek into the effect a body has on the drug product as it moves through different compartments. Hence, PK analysis has several applications in clinical research, academic studies, and clinical medicine. Let us study how PK services employ pharmacokinetic testing to understand drug behavior in the drug discovery process. The current article simplifies PK’s role by highlighting PK analysis through different drug discovery and development processes.
Non Clinical pharmacokinetic analysis
Before beginning human studies, pharmacokinetic services gather numerous in vivo and in vitro data. Ultimately, toxicokinetic analysis through single and repeated-dose toxicity studies provides early doses for in-human studies. Although PK data from animal models are generated through nonclinical studies, toxicokinetic studies produce a substantial portion of PK data. This data is crucial for designing subsequent human studies.
Depending on the data observed through early PK analysis, researchers can utilize several methods to determine the starting doses for later human studies. These methods can include identifying the no observed adverse effect level or employing complex scaling models to anticipate human outcomes.
Clinical pharmacokinetic studies
Generally, the clinical drug development phase comprises three phases, Phase I, II, and III. Once sponsors identify a new drug, and after adequate in vitro and animal studies, an IND application is filed for seeking approval to test the drug in human participants.
During phase I studies, the drug is administered to a small healthy population to assess the therapeutic and safety profile of the drug product. These studies begin with lower drug concentration and continuously escalate till it reaches toxic levels. These studies include first inhuman studies, single ascending dose studies (SAD), and multiple ascending dose studies (MAD).
The primary aim of the first-in-human studies is to identify safe levels and monitor toxicity, especially related to morbidity or mortality. Generally, first-in-human studies are SAD studies. In these studies, a small number of participants are administered the drug or placebo, and toxicity and safety levels are monitored through several physiological and biochemical tests. Once sponsors identify a safe drug dose, a higher dose is administered. In this manner, the drug doses are increased ascendingly. Once SAD studies are completed, sponsors move on to MAD studies. As most drugs are designed for repeated administration, MAD studies are crucial in understanding drug behavior over repeated use.
Must Read: The Role of PK Labs in Clinical Trial Design and Execution
Phase II studies not only assess drug safety and efficacy, but researchers test the drug product in the target patient population. PK studies help determine the changes in drug behavior between the target patient population and healthy subjects. Finally, Phase III studies evaluate the drug in a larger patient population. PK studies at this stage are usually performed for confirmatory purposes.
