Receptor Half-Life

Receptor half-life, \(t_{1/2,R}\), defines the degradation rate or turnover rate of a membrane receptor. Most models in Assess treat internalization and degradation as a single process. When the target of a drug is a receptor, \(t_{1/2, R}\) plays a role in target mediated drug disposition (TMDD).

Receptor Half-Life in Assess

The most direct measurements of receptor half-life are in vitro measurements of protein levels over time in the presence of cycloheximide, an inhibitor of protein synthesis. Other assays include pulse-chase and flow cytometry or imaging based assays of internalization using antibodies. Considerations when interpreting experiments include whether presence of ligand or antibody reagents altered the internalization/degradation behavior of the receptor. For very stable receptors, the half-life of the cells expressing the receptors may be the more appropriate rate to use in the model.