A pharmacokinetic study provides the basis for determining drug exposures in the body over time. PK parameters are used in the evaluation of the absorption, distribution, metabolism, and excretion (ADME) processes of drugs.
In simpler terms, a pharmacokinetics study focuses on understanding the effect a body has on the administered drug product. By exploring individual ADME components, pharmacokinetics labs help clinicians prescribe the correct doses that will generate the highest benefit but with the least associated risk factors. Besides, pharmacokinetic studies aid in adjusting the drug doses depending on individual physiology and lifestyle. Hence, PK sample analysis is crucial for the success of a drug development project. From drug discovery and preclinical studies to clinical trials, pharmacokinetic assays are employed at every stage of drug development. Let us explore the importance of PK in clinical research through ADME studies.
Absorption brings an administered drug product into the systemic circulation. Absorption affects the concentration and speed at which a drug reaches its target location. Clinical pharmacokinetic services employ different administration methods to generate clinical trial PK data. These routes of administration include oral, intramuscular, intravenous, subcutaneous, intrathecal, rectal, buccal, ocular, vaginal, inhaled, otic, transdermal, and nebulized. Each method has its advantages and limitations during PK analysis in clinical trials.
Absorption also includes liberating the active ingredient from the pharmaceutical drug form. Pharmacokinetics in clinical trials focuses on drug liberation, especially for oral medications. For example, the oral medication may reside in the throat or esophagus for an extended period after being ingested. This delay may damage the mucosa and impede the onset of drug effects. Besides, the low pH in the stomach may chemically react with the drugs even before they reach systemic circulation. Therefore, pharmacokinetic services are concerned, particularly with drug absorption and liberation.
Drug distribution varies from individual to individual. This variation is based on the drug properties and individual physiology. Hence, diffusion and convection are the primary factors affecting PK sample analysis in clinical trials. Moreover, these factors are affected by the size, binding kinetics, and polarity of the drug and the fluid status and body habitus of the patient. The primary aim of distribution in PK trials is to achieve effective drug concentration. For a drug product to be effective and active, it must reach its desired compartmental destination based on the volume of distribution and not protein-bound concentration.
Metabolism is the next step in a PK study clinical trial. It is the action of segregating the drug compound into components. Metabolism converts a drug compound into more water-soluble components and progresses them to renal clearance. It also metabolizes a prodrug into its active metabolites. Each body compartment, such as skin, plasma, gastrointestinal tract, lungs, and kidneys, has its metabolism strategy. PK labs and PK CROs focus on phase I and II reactions in the liver, as most of the metabolism occurs in the liver.
Excretion is the final phase of PK evaluations in clinical trials. It is through excretion that a drug is eliminated from the system. Generally, kidneys are common excretory organs. Although, certain drugs can be excreted through the skin, lungs, or gastrointestinal tract. However, pharmacokinetic CROs are always focused on complications associated with the reabsorption of specific compounds. In conclusion, PK assays are essential in generating ADME data.