TY - JOUR T1 - A dose-response study of nilotinib and imatinib in experimental pulmonary hypertension JF - European Respiratory Journal JO - Eur Respir J VL - 40 IS - Suppl 56 SP - P3900 AU - Marie-Camille Chaumais AU - Frederic Perros AU - Mathieu Molimard AU - Stephane Bouchet AU - Peter Dorfmuller AU - Christophe Guignabert AU - Sylvia Cohen-Kaminsky AU - Marc Humbert AU - David Montani Y1 - 2012/09/01 UR - http://erj.ersjournals.com/content/40/Suppl_56/P3900.abstract N2 - Introduction: Platelet derived growth factor (PDGF) and c-kit are involved in the pathophysiology of pulmonary hypertension (PH). Tyrosine kinase inhibitor (TKI) targeting PDGF receptors and c-kit such as imatinib (Im) and nilotinib (Nil) are currently tested in PH.Aims and objectives:To test the efficacy of Nil and Im in experimental PH.Methods: Sprague-Dawley rats were analyzed, corresponding to controls (Cont), animals exposed to MCT, MCT and treated with Im at 50 or 100 mg/Kg/j (MCT+Im50-MCT+Im100), MCT and treated with Nil at 40, 80 or 120 mg/Kg/j (MCT+Nil40-MCT+Nil80-MCT+Nil120). TKI were administered from day 21 to 35 after MCT. Serum kinetics concentrations (SKC) of TKI were performed at day 28. At day 35 hemodynamic parameters, right cardiac hypertrophy and pulmonary vascular remodelling were studied.Results: SCK showed that Im50,Nil40 and Nil80 corresponded to human drug concentrations. A dose-response improvement in hemodynamic parameters and medial wall thickness was observed with Im and Nil.View this table:Table 1Conclusion: Dose-dependent improvements of experimental PH are observed with Nil and Im. ER -