Molecules, Vol. 26, Pages 5602: In-Vivo Analysis and Model-Based Prediction of Tensides` InFluence on Drug Absorption (Molecules)

Depending on their concentrations the surface-active substances, tensides (surfactants) can positively or negatively influence the drug absorption, which is widely used in the design of the dosage forms with controlled release. A problem is that the (in-vivo) rate of absorption cannot be directly measured and for that reason, it is frequently substituted by evaluation of the (in-vitro) dissolution. On other hand, a suitably designed pharmacokinetic model can directly predict virtually all pharmacokinetic quantities including both the rate of absorption and fraction of the dose reaching the blood circulation. The paper presents a new approach to the analysis of the rate of drug absorption and shows its superiority over traditional in-vivo approaches. Both the in-vivo analysis and model-based prediction of the tenside (monolaurin of sucrose) influence on the rate of absorption of the drug (sulfathiazole) after instantaneous per-oral administration to rats are discussed. It was found that 0.001% solution of tenside can increase the rate of absorption by cca 50% and a two-fold increase in absolute bioavailability can be reached. Attention is also devoted to the formal requirements laid on the model`s structure and its identifiability. The systematic design, substantiation and validation of a parsimonious predictive model that confirms in-vivo results are presented. The match between in-vivo observations and model-based predictions is demonstrated. The frequently overlooked metaphysics lying behind the compartmental modelling is briefly explained.