A new Gastro-Intestinal Model to Study Drugs Bioavailability

This work focuses on a new mathematical model which describes the gastro-intestinal absorption of drugs and the effect of food interactions on drugs bioavailability. The model structure consists of five compartments (stomach, duodenum, jejunum feeding, intestine and blood) simulated though different in-series reactors. All the enzymatic reactions taking place in the gastro-intestinal system are described through the Michaelis-Menten kinetic equations. The model has been tested for drug administration (paracetamol and ketoprofen) with and without the meal digestion. The model has been validated through pharmacokinetics curves obtained from in vivo tests (reported in the literature) and used to simulate the drug absorption dynamics in different conditions. The maximum blood concentration were 0.153 mmol L-1 and 0.0243 mmol L-1, respectively for paracetamol and ketoprofen. The time to reach the maximum concentration for the paracetamol and ketoprofen was around 55 min. In case of contemporary meal digestion, the maximum concentration of paracetamol in the blood was 0.100 mmol L-1 and 0.0135 mmol L-1 for ketoprofen; the time to reach the maximum concentration was 3 h and 45 min for paracetamol and 3 h and 35 min for ketoprofen. The drugs showed different pharmacokinetics, in agreement with the literature, during the digestion of food. To show the predictive capacity of the model, the simulations were also compared against additional experimental data (obtained from in vivo tests available in the literature) relative to ketoprofen administration with food.