RESUMEN
Preclinical and clinical investigation on proteasome as a druggable target in cancer has led to the development of proteasome inhibitors (PIs) with different pharmacodynamic and pharmacokinetic properties. For example, carfilzomib has a better safety profile and a lower risk of clinically relevant drug-drug interactions than bortezomib, whereas ixazomib can be orally administered on a weekly basis due to a very long elimination half-life and high systemic exposure. The purpose of this review article is to elucidate the quantitative and qualitative differences in potency, selectivity, pharmacokinetics, safety and drug-drug interactions of clinically validated PIs to provide useful information for their clinical use in real life setting.
Asunto(s)
Antineoplásicos/uso terapéutico , Inhibidores de Proteasoma/uso terapéutico , Animales , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Compuestos de Boro/efectos adversos , Compuestos de Boro/farmacocinética , Compuestos de Boro/farmacología , Compuestos de Boro/uso terapéutico , Bortezomib/efectos adversos , Bortezomib/farmacocinética , Bortezomib/farmacología , Bortezomib/uso terapéutico , Interacciones Farmacológicas , Glicina/efectos adversos , Glicina/análogos & derivados , Glicina/farmacocinética , Glicina/farmacología , Glicina/uso terapéutico , Humanos , Mieloma Múltiple/tratamiento farmacológico , Oligopéptidos/efectos adversos , Oligopéptidos/farmacocinética , Oligopéptidos/farmacología , Oligopéptidos/uso terapéutico , Inhibidores de Proteasoma/efectos adversos , Inhibidores de Proteasoma/farmacocinética , Inhibidores de Proteasoma/farmacologíaRESUMEN
c-Met inhibitors are a class of drugs that include nonselective and selective molecules. These drugs can differ in terms of pharmacodynamic and pharmacokinetic properties that may be clinically relevant. c-Met inhibitors with high potency and selectivity may allow achieving optimal c-Met inhibition in c-Met-driven tumors while reducing unwanted off-target toxicities due to activation of multiple kinases. Nonselective drugs can instead be considered in tumors that also recognize other drivers (e.g., ALK, ROS, VEGF). Improved understanding of the clinical pharmacokinetics of c-Met inhibitors can help avoid drug-drug interactions and optimize schedules for continuous in vivo inhibition of c-Met phosphorylation. The current review article provides a detailed overview of the clinical pharmacology of molecules used in c-Met-driven tumors.