摘要
目的:为了解三氧化二砷经静脉用药在体内的药物代谢以及对人体的毒副作用。方法:用气相色谱法对8例用三氧化二砷静脉滴注治疗复发的急性早幼粒细胞白血病(APL)患者进行了药代动力学研究,同时监测了尿砷排泄及末梢砷蓄积情况。持续2小时静脉滴注10mg三氧化二砷注射液,测得高峰血浓度Cpmax为0.94±0.37mg/L,达峰时间Tpeak为4小时,血浆浓度分布半衰期T1/2α为0.89±0.29小时,消除半衰期T1/2β为12.13±3.31小时,系统清除率CLs为1.43±0.17L/h,表观分布容积Vc为3.83±0.45L,浓度-时间曲线下面积(AUC)为7.25±0.97mg·h/L。在持续用药过程中,药代动力学参数基本保持一致。疗程中,24小时尿砷排泄量为每日给药量的1%~8%,末梢砷蓄积上升较明显,最高时可达用药前5~7倍。停药后尿砷排泄和末梢砷蓄积即开始逐步下降。结论:三氧化二砷是一种治疗APL相对安全而有效的药物,但在人体头发和指(趾)甲内存在一定的蓄积作用。
Objective:In order to study the pharmacokinetics and metabolism of arsenic trioxide(As 2O 3 ),and its major side effects.Methods:The clinical pharmacokinetics of intravenous As 2O 3 in 8 relapsed acute promyelocytic leukemia (APL) patients were studied by Gas phase chromotography.Results:① After 2 hour intravenous drips of 10mg As 2O 3 , drug plasma maximal concentration (Cpmax) was 0.94±0.37mg/L(±s),time to peak concentration(Tp)was 4hrs,T1/2 α and T1/2β were 0.89±0.29hrs and 12.13±3.31hrs,respectively,apparent volume of distribution(Vc)was3.83±0.45L,system clearance(CLs)was 1.43±0.17L/h and area under curve (AUC) was 7.25±0.97mg·h/L. Importantly,the continuous administration of As 2 O 3 did not alter the pharmacokinetic behaviors.② During As 2O 3 therapy, 24 hour arsenic content in urine accounted for 1%~8% of the total dose (10mg) per day.And it decreased gradually after drug withdrawal.③ Arsenic contents in nail and hair were increased continuously during As 2O 3 therapy.The peak concentrations could be five to seven fold higher than that pre treatment.It also decreased gradually after drug with drawal .Conclusion:As 2O 3 is a relatively safe and effective drug in the treatment of APL patients,in spite of certain accumulation in some tissues.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
1997年第5期250-253,共4页
Chinese Journal of Hematology
基金
国家自然科学基金
卫生部优秀科技人才专项基金
上海市科技启明星计划
上海血液学研究所胡应洲基金
关键词
砷剂
药代动力学
急性
白血病
Arsenicals
Pharmacokinetics
Leukemia
myeloid
acute