Chapter 37 - Pharmacokinetic Methods

Abstract

Considerable resources are dedicated to pharmacokinetics (PK) studies in drug discovery. Advancement criteria in drug discovery and development usually include guidelines for the major PK parameters. PK behavior represents a composite of the underlying physicochemical and biochemical properties of the compound in the dynamic living system. Individual PK parameters can be used as guides for diagnosing the properties of the compound in order to improve performance by structural modification. Discovery methods for animal PK studies utilize all of the techniques that are applied for human clinical PK study samples. Pharmacokinetic studies in drug discovery typically dose two to four animals with a test compound in a generic formulation. The large number of compounds studied in drug discovery has stimulated interest in accelerated methods that increase the throughput of pharmacokinetic analysis. Samples from discrete dosing experiments are sometimes mixed for processing, commonly termed pooling. This allows for less sample preparation and LC/MS/MS analyses. It is necessary to pool only compounds of different molecular weight. The adoption of LC/MS/MS quantitation for PK studies in the early 1990s greatly accelerated the speed and sensitivity of the analyses. An example of hypothetical pharmacokinetic data from an experiment is provided.