Pharmacokinetic services are crucial for the process of drug development. Pharmacokinetic studies evaluate drug movement through the body. It does so by evaluating drug exposure over time. Pharmacokinetic studies could be modified and supplemented to assess different parameters, such as PK ADA assay in immunogenicity testing.
Pharmacokinetic services often complement PK studies with pharmacodynamic evaluations. Pharmacodynamic studies are concerned with understanding pharmacological responses once a drug has reached its site of action. Pharmacokinetic services perform relevant PK/PD assay to help determine the duration, onset, and magnitude of a drug’s effect. The current article describes pharmacokinetic services and their role in drug development.
Pharmacokinetic Services in Drug Development
Each patient uniquely influences on the processing of a drug product in the body. These individual factors include weight, sex, age, and genetics. Additionally, the minimum plasma concentration and the desired pharmacological response at that concentration vary among patients. Therefore, researchers must design the dosing regimen based on PK/PD data and ensure that most of the patient population attains adequate therapeutic exposure without intolerable adverse effects.
Moreover, drug metabolism data, and pharmacokinetic evaluations, are crucial to understanding drug biotransformation in relation to drug safety and efficacy. Drug metabolism and pharmacokinetic studies help drug developers evaluate drug properties and confirm that the administrated drug clears from the body without toxic effects and harmful metabolites. Pharmacokinetic services employ several in vitro and in vivo evaluations to predict potential risk factors early during the drug discovery and development phase and help researchers make informed decisions.
Generally, PK is described through a plasma concentration and time curve. However, the pharmacokinetic profile of a drug product includes all basic ADME processes. The ADME properties of a drug product, along with other pharmacokinetic components, can help decision-makers assess the efficacy and safety of drug therapy. An optimal pharmacokinetic profile demonstrates that a drug compound, when administered at a given dose, achieves the required concentration to elicit a desired biological response for a sufficient period in the target organ. Moreover, pharmacokinetic services can identify soft spots of a drug product in metabolic pathways. For example, in vitro and in vivo data demonstrating short half-life, low bioavailability, and high clearance indicate suboptimal pharmacodynamic effects.
The body performs an enzymatic reaction to convert a drug into its metabolites. The primary function of this process is to convert a lipophilic molecule into a more water-soluble component. Humans and animals may metabolize the compounds in unique ways. Hence drug metabolism studies are a crucial component of preclinical studies.
In vitro studies allow researchers to collect drug metabolism data and answer relevant questions about drug interaction with animal or human cells. There are three primary in vitro drug metabolism studies, namely metabolic stability, metabolic characterization, and reaction phenotyping. In each of these studies, researchers can employ several animal models. Comparing toxicity data among animal models and human studies helps researchers finalize an animal species for in vivo and in vitro studies. Moreover, enzyme inhibition and induction are two additional studies researchers employ to investigate drug-metabolizing enzymes.
Pharmacokinetic services also focus on in vivo studies to evaluate the ADME properties of a drug product. In vivo studies are crucial to assess the parent drug and determine its potential toxicity before beginning first-in-human trials. These studies help define the root of administration, the choice of preclinical species, and the starting doses for subsequent clinical trials.
