Pharmaceutical companies face a challenge when developing drugs that may be used to treat newborns, infants, and children due to the ethical concerns of including these groups in clinical trials. Modeling and simulation can accelerate the development of pediatric medicines
Quetiapine is an atypical antipsychotic drug for the treatment of schizophrenia, bipolar disorder, major depressive disorder and generalized anxiety disorder. An immediate-release formulation of quetiapine was first approved by the FDA in 1997 and has been extensively studied in adults, children and adolescents. Regulatory approval for the extended-release formulation was granted for use in adults, with the requirement that pediatric studies must be carried out for children over the age of 12.
Various factors influence the bioavailability of different formulations including the release of the active ingredient, its dissolution and permeability across the GI tract as well as intestinal metabolism. Furthermore, alterations in pharmacokinetics in children can be due to differences in absorption and transit rate, organ size, blood flow, tissue composition and metabolic capacity at various developmental stages. The challenge was to integrate the available in vitro ADME, physiochemical and clinical data into PBPK models to predict the effects of age and formulation on the pharmacokinetics of quetiapine in young subjects.