6-巯嘌呤细胞药理学研究对急性淋巴细胞白血病治疗的指导作用  

6-MP intracellular pharmacokinetics study in children with acute lymphoblastic leukemia

作　　者：马晓莉[1] 胡亚美[1] 吴敏媛[1] 李菊[1] 

机构地区：[1]首都医科大学附属北京儿童医院血液中心,100045

出　　处：《中华儿科杂志》2001年第3期160-163,共4页Chinese Journal of Pediatrics

摘　　要：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 6Objective Setting up a simple, quick, accurate method for cellular pharmacological study of 6 mercatopurine (6 MP). Methods Three kinds of 6 MP intracellular metabolites in RBC: 6 thioguanine nucleotide (6 TGN), 6 thioinosine monophosphate (6 TIMP), 6 methylmercatopurine (6 MeMP ) were measured by using reversed phase high performance liquid chromatography. Samples from 31 acute lymphoblastic leukemia (ALL) remission children with 6 MP treatment [50～75 mg/(m 2·d)] at least 2 months were collected No intensive chemotherapy was given in this period Results There were wide variation in measurable concentrations of two metabolites: 6 TGN ranged from 50 to 692pmol per 8×10 8 RBC Even when the same dose of 6 MP was used it still showed great variability ( CV =72%) 6 MeMP ranged from 0 7 to 29 1nmol per 8×10 8 RBC A negative correlation between 6 TGN and 6 MeMP was apparent ( r =-0 582 9, P =0 002) For patients receiving an unchanged dose of 6 MP, positive correlation could be demonstrated between the concentration of 6 TGN and the total dose of 6 MP There was also a correlation between 6 TGN and post treatment WBC 6 PGN and absolute neutrophil count ( r =-0 668 1, P =0 004; r =-0 656 4, P =0 003) Multivariate analysis showed the 6 TGN concentration variation was independent of diagnostic WBC count, age, cell immunological phenotype and duration of remission at the time of 6 TGN assay Conclusion These findings support that 6 MP cellular pharmacological variability is probably responsible for either severe myelo toxicity or therapeutic failure we have seen in clinic 6 TGN monitoring may give a better reference of the treatment intensity and also provide evidence for following up the relationship between the cellular pharmacology of 6 MP and risk of relapse in childhood ALL

关 键 词：6-疏嘌呤 急性淋巴细胞白血病 药物治疗 药理学 

分 类 号：R733.71[医药卫生—肿瘤] R730.53[医药卫生—临床医学]