Prediction of Local Drug Exposure of Dry Powder Inhaler CXG87 (budesonide/formoterol) Using Physiologically‐Based Pharmacokinetic Model

Inhaled formulations are the first choices for treating asthma and chronic obstructive pulmonary disease (COPD). Both local and systemic exposures need to be considered when assessing the efficacy and safety of inhaled drugs. Physiologically-based pharmacokinetic (PBPK) models were constructed and verified for budesonide and formoterol with different inhalation devices, CXG87 (test (T) formulation) and Symbicort® Turbuhaler® (reference (R) formulation). The models were then used to evaluate local exposures at different peak inspiratory flow rates (PIFRs) and dose conditions. Local exposures of CXG87 were comparable to the R formulation at PIFR 50-80 L/min at the dose of 200 μg/6 μg (budesonide/ formoterol fumarate), which was determined as the recommended dose. At this dose, CXG87 had local exposure advantages compared with the R formulation at PIFR 30-50 L/min and better local exposure stability at PIFR 30-80 L/min in the indication population. The simulation results indicated that 200 μg/6 μg can be selected as the study dose in the subsequent clinical study of CXG87 in indication patients. In addition, the clinical study could also include a lower flow rate (30-50 L/min) patient population to further evaluate the advantages of the modified formulation CXG87. This is the first study to predict CXG87 local exposure by a verified PBPK model.