A sharp fluctuation in peripheral blood cells shortly after dasatinib administration

Int J Hematol. 2012 Aug;96(2):194-9. doi: 10.1007/s12185-012-1138-2. Epub 2012 Jul 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Blood Cells / drug effects*
  • Blood Cells / metabolism
  • Blood Platelets / drug effects
  • Cell Adhesion Molecules / metabolism
  • Dasatinib
  • Humans
  • Leukemia / blood
  • Leukemia / drug therapy
  • Leukocyte Count
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Middle Aged
  • Platelet Count
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology*
  • Thiazoles / administration & dosage
  • Thiazoles / pharmacokinetics
  • Thiazoles / pharmacology*
  • Time Factors

Substances

  • Antineoplastic Agents
  • Cell Adhesion Molecules
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Thiazoles
  • Dasatinib