TY - JOUR T1 - Population pharmacokinetics of imatinib in patients with pulmonary arterial hypertension JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P4065 AU - Thomas Bouillon AU - Didier Renard AU - Ping Zhou AU - Gerard Flesch AU - Debbie Quinn Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P4065.abstract N2 - Introduction: Pulmonary arterial hypertension (PAH) results in increased pulmonary vascular resistance, right ventricular failure and eventually death. Imatinib is a tyrosine kinase inhibitor which may have efficacy in the treatment of PAH. This study evaluated biochemical and physiological covariates affecting pharmacokinetics of imatinib in patients with PAHMethods: Pharmacokinetic data were analyzed from 98 PAH patients receiving 200 mg imatinib (2 weeks), followed with 400 mg imatinib, if tolerated well, until 24 weeks in a phase III randomized study (IMPRES). Imatinib population pharmacokinetics were described by a one-compartment disposition model with zero order input and inter-individual variability (IIV) on apparent clearance (CL/F) and volume of distribution (V/F). Covariates included age, gender, race, hemoglobin, white blood cell count, and co-medications (CYP3A4 inhibitors such as sildenafil and bosentan)Results: Parameter estimates of the final population pharmacokinetic model for imatinib in PAH patients are presented belowView this table:CL/F in absence of bosentan was similar in PAH, chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) patients. V/F was almost identical to that in CML patients, approximately 40% larger in GIST patients. Hemoglobin levels correlated with both CL/F and V/FConclusion: Comparable population pharmacokinetic parameters are reported with imatinib in PAH, CML and GIST patients. ER -