Schematic illustration of exposure-driven response models (upper row) and biophase-driven response (bottom row). Schematic illustration of exposure-driven response models (upper row) and biophase-driven response (bottom row). The plasma concentration is typically the (proxy) driver of the pharmacological model in an exposure (C)–driven model, in contrast to the DRT model in which a biophase compartment model serves as a surrogate for drug exposure. In DRT analyses, information about dose, route, and rate are pivotal for a stringent analysis. The structure of the hypothetical biophase model is assumed to be extracted from the time course(s) of biologic response-time course as such. The underlying assumption about pharmacological response-time data is that some kind of kinetic information is embedded into them, which then may be approximated by the biophase model. In turn, this represents the potential time course (shape) of the total amount of drug in the body that is expected to “drive” the measured pharmacological response. The gray shaded areas are inferred from experimental concentration-time data (upper row) or dosing information (bottom row) coupled to response-time courses. The response-time courses in the DRT analysis provide the extra “kinetic” information to the model that concentration-driven pharmacodynamic models do not need. PO, per oral; SC, subcutaneous. Johan Gabrielsson et al. Pharmacol Rev 2019;71:89-122 Copyright © 2018 by The Author(s)‏