Physiologically-Based Pharmacokinetic Model on the Oral Drug Absorption in Roux-en-Y Gastric Bypass Bariatric Patients: Amoxicillin Tablet and Suspension.

The potential of a physiologically-based pharmacokinetic (PBPK) model to predict oral amoxicillin bioavailability, by considering the physiological changes after "Roux-en-Y gastric bypass" (RYGB) surgery in bariatric patients, was evaluated. A middle-out approach for parameter estimations was undertaken using , , and data. The observed versus predicted plasma concentrations and the model sensitivity of the simulated parameters of AUC and of amoxicillin (AMX) were used to confirm the reliability of the estimation. The model considers that a drug-transporter () in the initial segments of the normal intestine plays a significant role in the AMX absorption. A lower fraction absorbed () was observed in RYGB patients (54.43% for suspension and 45.21% for tablets) compared to healthy subjects (77.48% capsule). Furthermore, the tablet formulation presented a lower dissolved fraction () and compared to the suspension formulation of AMX in RYGB patients (91.70% and 45.21% versus 99.92% and 54.43%, respectively). The AUC and were sensitive to changes in , Peff, and for both healthy and RYGB models. Additionally, AUC and were also sensitive to changes in the parameter for tablet formulation in RYGB patients. The PBPK model showed a reduction in AMX bioavailability as a consequence of reduced intestinal length after RYGB surgery. Additionally, the difference in the predicted and between suspension and tablet suggests that liquid formulations are preferable in postbariatric patients.