title: Measurement of granulocyte pharmacodynamics in whole blood by flow cytometry.
abstract: During the Phase I/II assessment of new therapies with the potential to suppress eosinophil and neutrophil inflammation, there is a need to assess the peripheral blood pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the drug. This has relevance in respiratory disease since drugs that target eosinophillic inflammation are in development for asthma; whereas neutrophil-directed therapies are being introduced for treatment of chronic obstructive airways disease (COPD). Pharmacokinetic evaluation is required to determine the concentration of drug substance (and possibly metabolites) in peripheral blood at intervals following single or repeated dosing. Pharmacodynamic assessment is also required since many drug substances have a duration of action which is prolonged beyond the time when drug substance is detectable in the blood (see Fig. 1). Fig. 1. Whole blood pharmacodynamics. In preclinical studies, animal or human blood is treated with test agents. In clinical studies, human subjects are treated with drug and blood removed for analysis. GAFS, gated autofluorescence forward scatter; PK, pharmacokinetics; PD, pharmacoldynamics.
authors.affiliation: Royal Brompton Clinical Studies Unit, National Heart and Lung Institute, Imperial College School of Science, Technology and Medicine, London, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Bryan
authors.forename: M J
authors.initials: MJ
authors.lastname: Leckie
authors.forename: G
authors.initials: G
authors.lastname: Jenkins
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: T J
authors.initials: TJ
authors.lastname: Williams
authors.forename: I
authors.initials: I
authors.lastname: Sabroe
authors.forename: T T
authors.initials: TT
authors.lastname: Hansel