Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Int J Hematol. 2012 Aug;96(2):194-9. doi: 10.1007/s12185-012-1138-2. Epub 2012 Jul 15.
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.
达沙替尼是一种酪氨酸激酶抑制剂，其血浆半衰期较短，抑制谱更广，包括针对Src 家族激酶。我们监测了达沙替尼的外周血计数和血清浓度随时间的变化。有趣的是，我们发现血细胞有短暂的波动，与达沙替尼水平相关。我们比较了 23 名患者在服用达沙替尼前的外周血计数与服药后 2 小时的血样中的计数。总白细胞（WBC）从基线增加了 2186 ± 1960/μL（P = 0.00002），而血小板从基线的 185 ± 47×10(3)/μL 降至 164 ± 52×10(3)/μL（P = 0.0007）。接受伊马替尼或尼洛替尼治疗的患者未观察到类似现象。此外，与伊马替尼不同，达沙替尼在体内和体外均强烈抑制血液细胞上 CD18、CD62P 和 CD63 的表达。这些结果表明，该药物可能通过调节其在血液细胞上的特定黏附分子表达来影响体内血细胞的分布。
