论文部分内容阅读
目的 建立一种高效、快速、灵敏的方法 ,探讨 6 巯嘌呤 (6 MP)细胞药理学。方法 应用反相高效液相色谱分析技术 ,定量测定急性淋巴细胞白血病 (ALL)患儿红细胞内 6 MP三种代谢产物浓度 :6 巯嘌呤核苷酸 (6 TGN) ,6 次黄巯嘌呤单核苷酸 (6 TIMP)和 6 甲基巯嘌呤 (6 MeMP)。选择31例ALL缓解期随访的患儿 ,口服 6 MP 5 0～ 75mg (m2 ·d)治疗 2个月以上且期间未进行强化治疗者。结果 红细胞内 6 TGN和 6 MeMP浓度个体间差异很大。 6 TGN浓度为 5 0～ 6 92pmol 8× 10 8RBC ,口服相同剂量时个体间变异系数 (CV)为 72 %。6 MeMP浓度为 0 7～ 2 9 1nmol 8× 10 8RBC。 6 TGN与 6 MeMP大致成负相关 (r=- 0 5 82 9,P =0 0 0 2 ) ;口服 6 MP个体间耐受性差异很大 ,6 TGN浓度与 6 MP剂量无线性关系 ,而与剂量强度成正相关。 6 TGN浓度与治疗后白细胞数及中性粒细胞绝对值呈负相关 (r=- 0 6 6 81,P =0 0 0 4和r=- 0 6 5 6 4,P =0 0 0 3)。此外 ,6 TGN浓度与诊断时白细胞数、年龄、维持治疗时间、免疫分型等均无关。结论 6 MP的细胞药理学变异与其细胞毒作用有密切关系 ,红细胞内 6 TGN浓度能较好地反映 6 MP的治疗强度 ,而且可能为一种独立的影响疗效的因素。检测 6 MP细胞内
Objective To establish a highly efficient, rapid, and sensitive method to investigate the pharmacology of 6-purine (6 MP) cells. Methods The RP-HPLC method was used to quantitatively determine the concentration of 6 MPs in the erythrocytes of children with acute lymphoblastic leukemia (ALL): 6 purine nucleotides (6 TGN), 6 xanthine mononuclear Acid (6 TIMP) and 6 Methyl purine (6 MeMP). Thirty-one children with ALL who were followed up during the remission period were selected and treated with 6 MP 50-75 mg (m2 ·d) orally for more than 2 months without intensive treatment. Results The intracellular concentrations of 6 TGN and 6 MeMP in the red blood cells varied greatly between individuals. 6 The concentration of TGN was 5 0 to 6 92pmol 8×10 8RBC, and the inter-individual coefficient of variation (CV) was 72% at the same oral dose. The 6 MeMP concentration is 0 7 to 2 9 1 nmol 8×10 8 RBC. 6 TGN was roughly inversely related to 6 MeMP (r=- 0 582 2 9 , P =0 0 2 ); the tolerability of oral 6 MP individuals was very different, 6 TGN concentration was related to 6 MP dose of radioactivity, and Positive correlation with dose intensity. 6 The TGN concentration was negatively correlated with the number of leukocytes and the absolute value of neutrophil after treatment (r =- 0 6 6 81, P =0 0 0 4 and r =- 0 6 5 6 4, P =0 0 0 3). . In addition, 6 TGN concentrations were not related to the number of leukocytes at the time of diagnosis, age, duration of maintenance therapy, and immunophenotyping. Conclusion The cellular pharmacological variation of 6 MP is closely related to its cytotoxicity. The concentration of intracellular TGN in RBC can better reflect the therapeutic intensity of 6 MP, and may be an independent factor that influences the therapeutic effect. Detection within 6 MP cells