Mechanistic embedding of concise physiological absorption models for enhanced prediction in population pharmacokinetic modeling of oral ibuprofen.

Ibuprofen, a commonly used non-steroidal anti-inflammatory drug (NSAID), exhibits considerable variability in pharmacokinetics following oral administration, particularly during the absorption phase. This study aimed to enhance the mechanistic understanding of ibuprofen absorption by developing and integrating physiologically-informed models of absorption within a population pharmacokinetic (PopPK) framework. Using existing datasets of ibuprofen plasma concentrations, two one-compartment PopPK models with linear elimination were developed: the Sequential Absorption Pharmacokinetic (SAPK) model, which accounts for pH-dependent gastrointestinal absorption, and the Partial Absorption Pharmacokinetic (PAPK) model, which reflects absorption triggered by gastric emptying. Both models adequately described the observed concentration-time profiles and explained individual variability in absorption. These findings offer valuable insight into ibuprofen absorption kinetics and support the advancement of personalized dosing strategies.