Receptor activation using multi-biomarker pharmacokinetic/pharmacodynamic modelling

Abstract

receptor activation was evaluated using quinpirole as a paradigm compound. ), as well as plasma concentrations of 13 hormones and neuropeptides, were measured. Experiments were performed at day 1 and repeated after 7-day s.c. drug administration. PK/PD modelling was applied to identify the in vivo concentration-effect relations and neuroendocrine dynamics. receptor expression levels on the pituitary hormone-releasing cells predicted the concentration-effect relationship differences. Baseline levels (ACTH, prolactin, TSH), hormone release (ACTH) and potency (TSH) changed with treatment duration. agonists in clinical practice. Further development towards quantitative systems pharmacology models will eventually facilitate mechanistic drug development. BACKGROUND AND PURPOSE EXPERIMENTAL APPROACH KEY RESULTS CONCLUSIONS AND IMPLICATION