Predicting budesonide performance in healthy subjects and patients with Crohn's disease using biorelevant in vitro dissolution testing and PBPK modeling

Objectives: Drug product performance might be affected in Crohn's disease (CD) patients compared to healthy subjects due pathophysiological changes. Since a low number of clinical studies is performed this patient population, physiologically-based pharmacokinetic (PBPK) models with integrated results from biorelevant vitro dissolution could used assess differences the bioavailability drugs. Using approach, budesonide was as model drug and its CD predicted against observed data. The release tests, under versus conditions, revealed similar extent controlled-release formulation fasted state, whereas fed state lower CD. Differences physiology were identified literature their impact on investigated PBPK model, revealing highest simulated for reduced hepatic CYP3A4 enzyme abundance human serum albumin concentration. For patients, higher exposure population adapted agreement Budesonide successfully using modeling testing. Following predictions direction magnitude changes made other drugs guide prescribers adjust dosage regimens accordingly.