%0 Journal Article
%T Pharmacokinetics of dasatinib for Philadelphia-positive acute lymphocytic leukemia with acquired T315I mutation
%A Naoto Takahashi
%A Masatomo Miura
%A Stuart A Scott
%A Takenori Niioka
%A Kenichi Sawada
%J Journal of Hematology & Oncology
%D 2012
%I BioMed Central
%R 10.1186/1756-8722-5-23
%X To determine whether plasma dasatinib pharmacokinetics influences the emergence of BCR-ABL mutations, we measured plasma dasatinib levels in 11 Ph£¿+£¿ALL patients undergoing dasatinib monotherapy.Bone marrow relapse occurred in 5 of the 11 Ph£¿+£¿ALL patients (45%). Importantly, a T315I mutation was detected in 4 of the 5 relapsed patients, despite the absence of BCR-ABL mutations in any patient at baseline. The median plasma concentration at 2 hours (C2h), the median plasma maximum concentration (Cmax), and the median area under the observed plasma concentration-time curve from 0 to 4 hours (AUC0-4) were all significantly lower in patients with T315I than those without the mutation (C2h, 22.3£¿ng/mL vs. 111.6£¿ng/mL, P£¿=£¿0.0242; Cmax, 43.8£¿ng/mL vs. 112.4£¿ng/mL, P£¿=£¿0.0242; AUC0-4, 108.3£¿ng¡¤h/mL vs. 268.3£¿ng¡¤h/mL, P£¿=£¿0.0061, respectively).These data indicate that the emergence of the T315I mutation among Ph£¿+£¿ALL patients treated with dasatinib is, in part, dependent on plasma dasatinib pharmacokinetics. Notably, these data also suggest that newly acquired BCR-ABL mutations may be inhibited by an increased exposure of dasatinib.
%K Dasatinib
%K Ph positive acute lymphoid leukemia
%K T315I
%K Pharmacokinetics
%U http://www.jhoonline.org/content/5/1/23/abstract