Pharmacokinetics (PK) is defined as the branch of pharmacology dedicated to determination of the fate of substances administered to a living organism.
Pharmacokinetics refers to the movement of drug into, through, and out of the body—the time course of its liberation, absorption, distribution, metabolism, and excretion (ADME).
- Liberation – the process of release of a drug from the pharmaceutical formulation
- Absorption – the process of a substance entering the blood circulation.
- Distribution – the dispersion or dissemination of substances throughout the fluids and tissues of the body.
- Metabolism (or biotransformation, or inactivation) – the recognition by the organism that a foreign substance is present and the irreversible transformation of administered compounds into metabolites.
- Excretion – the removal of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue
Pharmacokinetics is essentially the study of how the organism affects the drug, whereas pharmacodynamics is the study of how a drug affects the body organism. Both together influence dosing, benefit, and adverse effects.
Bioanalysis is integral to our understanding of the pharmacokinetic profile of a therapeutic. The concentration/time data obtained from analysis of biological samples feeds the modeling of a drug’s fate in an organism.
As bioanalytical experts we are happy to work with any type of molecule ranging from conventional small molecules to biopharmaceuticals (large molecules). Most bioanalytical assays use blood-based matrices such as plasma or serum but we are equally comfortable working with non-routine matrices such as urine, CSF, feces and tissues as part of the assessment of distribution and excretion.
There has been an increasing focus on large molecule therapeutics in development and pharmaceutical companies have aligned their development pipelines more in that direction. The increasingly complex nature of the analytes under investigation has meant that bioanalytical has had to evolve to keep up. KCAS has built an expert team developing sensitive and selective assays using ligand binding technologies for quantitation of large molecules. These approaches are routinely applied for the bulk of our biomolecule PK support but they do not represent a panacea. Limited availability of quality reagents or presence of analogues mean that an alternative approach such as Hybrid LC-MS/MS may be more applicable. Combining the principles of ligand binding for target analyte enrichment with the selectivity offered by chromatography and mass spectrometry make it possible to determine low concentrations of large molecule analytes in the presence of other matrix components at similar levels to ligand binding.
The benefit of this is that we have two expert teams working with complementary analytical technologies under one roof. We can readily formulate the best approach for your large molecule PK project. The close proximity of the teams also means we can readily pivot between methodologies should we encounter major issues.
KCAS aims to be a collaborative team member when supporting your drug development program. We have built our core expertise to support all aspects of pharmacokinetics, independent of the size of the drug. To ensure that you get the output you want we are happy to provide non-compartmental PK modeling for non-clinical and clinical studies.