A sharp fluctuation in peripheral blood cells shortly after dasatinib administration.
Dasatinib, a tyrosine kinase inhibitor, has a reduced plasma half-life and a more extensive inhibition profile, including targeting of Src family kinases. We monitored the peripheral blood count and the serum concentration of dasatinib over time. Interestingly, we found a transient fluctuation of blood cells, which correlated with the dasatinib level. The peripheral blood count before intake of dasatinib was compared with counts measured 2 h later in blood samples from 23 patients. Total white blood cells (WBCs) increased by 2,186 ± 1,960/μL from baseline (P = 0.00002), whereas platelets decreased from a baseline of 185 ± 47 × 10(3)/μL to 164 ± 52 × 10(3)/μL (P = 0.0007). Similar phenomena were not observed in patients treated with imatinib or nilotinib. In addition, in contrast to imatinib, dasatinib strongly attenuated the expression of CD18, CD62P and CD63 by blood cells both in vivo and in vitro. These results suggest that this drug may influence the distribution of blood cells in vivo by regulating its specific adhesion molecule expression on blood cells.
Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Jun
J
Imagawa
Hideo
H
Tanaka
Kana
K
Matsumoto
Kunihiko
K
Morita
Yuka
Y
Harada
Hironori
H
Harada
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000069439:Dasatinib; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000188:drug therapy; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D010976:Platelet Count; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013997:Time Factors
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib