Integration of a Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Tegoprazan and Its Metabolite: Application for Predicting Food Effect and Intragastric pH Alterations.

Abstract

A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model for tegoprazan and its major metabolite M1 was developed to predict PK and PD profiles under various scenarios. The PBPK model for tegoprazan and M1 was developed and predicted using the SimCYP® simulator and verified using clinical study data obtained after a single administration of tegoprazan. The established PBPK/PD model was used to predict PK profiles after repeated administrations of tegoprazan, postprandial PK profiles, and intragastric pH changes. The predicted tegoprazan and M1 concentration–time profiles fit the observed profiles well. The arithmetic mean ratios (95% confidence intervals) of the predicted to observed values for the area under the curve (AUC0–24 h), maximum plasma drug concentration (Cmax), and clearance (CL) for tegoprazan and M1 were within a 30% interval. Delayed time of maximum concentration (Tmax) and decreased Cmax were predicted in the postprandial PK profiles compared with the fasted state. This PBPK/PD model may be used to predict PK profiles after repeated tegoprazan administrations and to predict differences in physiological factors in the gastrointestinal tract or changes in gastric acid pH after tegoprazan administration.