RESUMEN
Developmental changes in children can affect drug disposition and clinical effects. A physiologically-based pharmacokinetic (PBPK) model is a mathematical model that can be used to predict blood drug concentrations in children and gain insight into age-dependent physiological differences in drug disposition impact. Pediatric PBPK (P-PBPK) models have attracted attention over the past decade. With the concerted efforts of academia, pharmaceutical companies, and regulatory agencies, there are more and more examples of pediatric clinical studies using PBPK models. Nevertheless, the number of P-PBPK models and their predictive performance still lag behind adult models. By referring to the literature, we study the process of children adapting to adult absorption, distribution, metabolism, and excretion (ADME) parameters and analyze the general principles of P-PBPK model establishment. In addition, we summarize the functions and application examples of commonly used P-PBPK modeling software to provide a basis for the rational application of modeling software.
RESUMEN
OBJECTIVE: To develop colon-targeting multi-dosage oral delivery system (mini tablet) using chitosan as the material for treatment of colon cancer. METHODS: Indomethacin (IN) was chosen as a model drug. Firstly, IN solid dispersion was prepared, then Eudragit-chitosan bilayer coated colon targeting mini tablets were prepared by direct compression method and coating technology. The release profiles of the targeting mini tablets in different release media were studied. Small animal in vivo fluorescence imaging investigation was used to sudy the transport and absorption in rats. Beagle dogs were used as animal model to study the pharmacokinetics and bioavailability of the mini tablets. RESULTS: The Eugragit-chitosan bilayer coated mini tablets maintained complete form when passing through the stomach and small intestine of rats, and targeted to the colon. The pharmacokinetic data in Beagle dogs showed that the mini tablets had delayed release and preserved steady absorption. CONCLUSION: The prepared Eudragit-chitosan bilayer coated multi dosage oral colon mini tablets showed good colon targeting effect and sustained release, which can provide important reference for the treatment of colon diseases.