A heterogeneous tube model of intestinal drug absorption based on probabilistic concepts

Purpose. To develop an approach based on computer simulations for the study of intestinal drug absorption. Methods. The drug flow in the gastrointestinal tract was simulated with a b iased random walk model in the heterogeneous tube model (Pharm. Res. 16, 87 -91, 1999), while probability concepts were used to describe the dissolutio n and absorption processes. An amount of drug was placed into the input end of the tube and allowed to flow, dissolve and absorb along the tube. Vario us drugs with a diversity in dissolution and permeability characteristics w ere considered. The fraction of dose absorbed (F-abs) was monitored as a fu nction of time measured in Monte Carlo steps (MCS). The absorption number A n was calculated from the mean intestinal transit time and the absorption r ate constant adhering to each of the drugs examined. Results. A correspondence between the probability factor used to simulate d rug absorption and the conventional absorption rate constant derived from t he analysis of data was established. For freely soluble drugs, the estimate s for F-abs derived from simulations using as an intestinal transit time 24 500 MCS (equivalent to 4.5 h) were in accord with the corresponding data ob tained from literature. For sparingly soluble drugs, a comparison of the no rmalized concentration profiles in the tube derived from the heterogeneous tube model and the classical macroscopic mass balance approach enabled the estimation of the dissolution probability factor for five drugs examined. T he prediction of F-abs can be accomplished using estimates for the absorpti on and the dissolution probability factors. Conclusions. A fully computerized approach which describes the flow, dissol ution and absorption of drug in the gastrointestinal tract in terms of prob ability concepts was developed. This approach can be used to predict F-abs for drugs with various solubility and permeability characteristics provided that probability factors for dissolution and absorption are available.