Membrane bioreactors for digestive system to study drugs absorption and bioavailability

This chapter describes a new gastro intestinal (GI) model, based on membrane bioreactors, able to evaluate the bioavailability of drugs, also in presence of food. The model includes the physiology of five compartments: stomach, duodenum, jejunum, colon, and blood. All the compartments are interconnected with valves that control the flux in input and output from the compartments (discontinuous running mode). The molecule passage in the blood occurs though a transmembrane flux. The simulation of GI absorption starts with the input of the bolus in the stomach. The emptying of the stomach is controlled by enzymatic reactions in the duodenum, therefore controlling this stage without any external function or parameters, but only using the physiological process. The parameters used work for the optimal condition of the reactions (pH in optimal range, presence of bile salts, etc.). Paracetamol and ketoprofen are the drugs implemented for model validation. The data obtained from the model are comparable with in vivo results from literature. The reference parameters are maximum concentration, time to enter and exit from therapeutic range, and time to reach the maximum concentration. The tests "with food" include a nutrient concentration to simulate a meal with 150 g of bread and 20 g of butter. The maximum concentration in blood for the test 1 is 0.153 mmol L- 1 for the paracetamol, while for ketoprofen it is 0.0243 mmol L- 1. The times to reach the maximum concentration for both the ketoprofen and paracetamol are about 55 min. In the presence of the meal, drugs show different pharmacokinetics. The maximum concentration for ketoprofen is 0.0135 mmol L- 1. The time to reach the maximum concentration is 3 h and 35 min.