Search

Live biotherapeutic products (LBPs) are human microbiome therapies showing promise in the clinic for a range of diseases and conditions. Describing the kinetics and behavior of LBPs poses a unique modeling challenge because, unlike traditional therapies, LBPs can expand, contract, and colonize the host digestive tract. Here, we present a novel cellular kinetic-pharmacodynamic quantitative systems pharmacology model of an LBP. The model describes bacterial growth and competition, vancomycin effects, binding and unbinding to the epithelial surface, and production and clearance of butyrate as a therapeutic metabolite. The model is calibrated and validated to published data from healthy volunteers. Using the model, we simulate the impact of treatment dose, frequency, and duration as well as vancomycin pretreatment on butyrate production. This model enables model-informed drug development and can be used for future microbiome therapies to inform decision making around antibiotic pretreatment, dose selection, loading dose, and dosing duration., (© 2023 Takeda Pharmaceuticals. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

This article is a comparative study of the institutionalization of the migration policy frameworks of post-Soviet states Armenia, Azerbaijan and Georgia since the collapse of the Soviet Union in 1991. All three countries share common historical legacies: a Soviet past, wars and conflicts, unemployment, high emigration, and commitment to integration into European bodies. To what extent do the migration policies of these three countries (driven by contextual forces, i.e. domestic challenges) address country-specific migration dynamics? Or are they imposed by the European Union? In which dimensions have the national policies on migration of Armenia, Azerbaijan and Georgia evolved, and around which issues have they converged or diverged? Have these trends led to an integration of migration policymaking at the regional level in the South Caucasus?