Investigational new drugs
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Investigational new drugs · Oct 2017
Pharmacokinetics and excretion of 14C-Plitidepsin in patients with advanced cancer.
Plitidepsin (Aplidin®) is a marine-derived anticancer compound currently investigated in phase III clinical trials. This article describes the distribution, metabolism and excretion of this novel agent and it mainly aims to identify the major routes of elimination. Six subjects were enrolled in a mass balance study during which radiolabelled plitidepsin was administered as a 3-h intravenous infusion. ⋯ TRA levels were 3.7 times higher in whole blood compared to plasma. Plitidepsin was widely distributed and plasma clearance was low. This study shows that red blood cells are a major distribution compartment and that the biliary route is the main route of total radioactivity excretion.
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Investigational new drugs · Oct 2017
Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia.
Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations in this gene are associated with poor overall survival. AXL plays a role in the activation of FLT3 and has been implicated in the pathogenesis of AML. ⋯ The decreased FLT3 activity and high intratumor distribution of gilteritinib translated to tumor regression and improved survival in xenograft and intra-bone marrow transplantation models of FLT3-driven AML. No overt toxicity was seen in mouse models treated with gilteritinib. These results indicate that gilteritinib may be an important next-generation FLT3 inhibitor for use in the treatment of FLT3 mutation-positive AML.