Abstract:
Objective: To detect the concentrations of cytosine arabinoside (Ara-C) and 1-β-D-arabinofuranosyluraci l (Ara-U) in plasma, at two hours, when high dose cytosine arabinoside (HD-AraC) intravenous drip was completed, in cases of acute leukemia (AL) and non-Hodgkin's lymphoma (NHL), and to analyze the correlation between activity of Ara-C-me-tabolizine enzymes and the concentrations of Ara-C and Ara-U in plasma. This study aimed to investigate the metabolic characteristics of Ara-C in vivo and the influence of key enzyme expression on the drug concentration in plasma during HD-AraC treatment for childhood hematological malignancies. Methods:High performance liquid chromatography (HPLC) was used to detect the concentrations of Ara-C and Ara-U in plasma, at two hours, when intravenous drip was completed, in 24cases, including21cases of AL and 3 cases of NHL. Deoxy-5-3 H-cytidine was employed to detect the deoxycytidine kinase (DCK) and cytidine deaminase (CDA) activity in these same cases. The relationship of the expression of key en zymes of Ara-C metabolism with the peak concentrations of Ara-C and Ara-U in plasma was also analyzed. Results:The ex-pression of CDA remarkably affected the peak concentrations of Ara-C and Ara-U in plasma ( P<0.05): patients with higher CDA activity had higher concentrations of Ara-U in plasma and lower concentrations of Ara-C in plasma; patients with lower CDA activity had lower concentrations of Ara-U in plasma and higher concentrations of Ara-C in plasma. No correlation was found between DCK expression and peak concentrations of Ara-C and Ara-U in plasma ( P>0.05). Conclusion:HD-AraC is a very effective protocol for childhood refractory hematological malignancies. But the effect of CDA expression on the peak concentrations of Ara-C and Ara-U may affect the therapeutic reaction of HD-AraC. Therefore, detecting the expression of CDA may provide reliable reference for clinical dose adjustment and individualized treatment.