BACKGROUND Imatinib can induce severe hepatotoxicity, in 1-5% of CML patients, many of whom need permanent imatinib discontinuation. DESIGN AND RESULTS We report 5 CML patients who developed grade 3-4 hepatotoxicity after 2-8 months in imatinib. Different aetiologies of liver damage were ruled out and toxicity recurred in 2 patients with further attempts at low dose imatinib. In all patients ...

BACKGROUND Tissue edema and endothelial barrier dysfunction as observed in sepsis and acute lung injury carry high morbidity and mortality, but currently lack specific therapy. In a recent case report, we described fast resolution of pulmonary edema on treatment with the tyrosine kinase inhibitor imatinib through an unknown mechanism. Here, we explored the effect of imatinib on endothelial barr...

Pankey EA, Thammasiboon S, Lasker GF, Baber S, Lasky JA, Kadowitz PJ. Imatinib attenuates monocrotaline pulmonary hypertension and has potent vasodilator activity in pulmonary and systemic vascular beds in the rat. Am J Physiol Heart Circ Physiol 305: H1288 –H1296, 2013. First published August 30, 2013; doi:10.1152/ajpheart.00329.2013.—Cardiovascular responses to the tyrosine kinase inhibitor i...

Purpose:Dasatinib andnilotinib are active in imatinib-resistant chronicmyelocytic leukemia (CML) and many patients undergo sequential treatment. We aimed at modeling sequential tyrosine kinase inhibitor (TKI) resistance in vitro to compare the sequences imatinib-nilotinib-dasatinib and imatinib-dasatinib-

Imatinib mesylate is a receptor kinase inhibitor approved by the Food and Drug Administration for the treatment of malignant metastatic and/or unresectable gastrointestinal stromal tumors and chronic myelogenous leukemia. Although imatinib is generally well tolerated, certain adverse drug reactions are common. These include gastrointestinal side-effects such as diarrhea, nausea and vomiting, as...

The BCR-ABL kinase inhibitor imatinib mesylate is currently the standard therapy for patients with chronic myeloid leukemia (CML). Despite the remarkable results achieved with imatinib for the treatment of CML, the emergence of resistance to this drug has become a significant problem. Mutations within the ABL kinase domain have been identified as the main mechanism of resistance to imatinib. Ot...

BACKGROUND Although treatment with imatinib in advanced gastrointestinal stromal tumor (GIST) patients has led to significant clinical benefits, the disease will eventually progress due to imatinib resistance. Treatment options after failure of first-line imatinib include imatinib dose escalation or shifting to sunitinib. However, there is no large-scale study to compare the efficacy difference...

The treatment of chronic myeloid leukemia (CML) has been revolutionized by the small molecule BCR-ABL-selective kinase inhibitor imatinib. Although imatinib is highly effective initially and generally well-tolerated, relapse is increasingly encountered clinically. Until recently, for the majority of CML patients with disease no longer responsive to imatinib, as well as for patients with imatini...

BACKGROUND Imatinib, a tyrosine kinase inhibitor currently approved for treatment of several malignancies, has been shown to be a substrate for multiple efflux-transporter proteins, including ABCB1 (P-glycoprotein) and ABCG2 (BCRP). The effect of inhibiting these transporters on tissue exposure to imatinib remains unclear. OBJECTIVE To assess the role of these transporters on drug disposition...

We have previously shown that imatinib uptake into chronic myeloid leukemia (CML) cells is dependent on human organic cation transporter 1 (hOCT1; SLC22A1), and that low hOCT1 expression is an important determinant of clinical outcome to imatinib treatment. We hypothesized that dasatinib might be transported differently than imatinib, possibly accounting for its favorable effects in imatinib-re...