过敏和沉默失活状态下门冬酰胺酶的药代动力学研究被引量：3

Pharmacokinetics of asparaginase in allergic and silent inactivation

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摘要目的通过门冬酰胺酶(Asp)活性检测,了解正常、过敏以及沉默失活状态下培门冬酰胺酶(Peg-asp)和欧文氏菌门冬酰胺酶(Erw-asp)的药代动力学并指导临床用药。方法单次肌注Peg-asp后,分别于注射后8d、15d、22d检测血清门冬酰胺酶(Asp)活性;单次注射Erw-asp后,分别于注射后24h、48h、72h、96h检测Asp活性。结果 206例急性淋巴细胞白血病患儿进行了957次Asp活性检测,其中66例患儿单次肌注Peg-asp 2000u/m^2,均能维持有效活性达3周;Pegasp用药后存在沉默失活现象,发生率5%左右;26例既往有普通大肠杆菌门冬酰胺酶(Ecoli-asp)过敏史的患儿换用Peg-asp后,Asp活性半衰期大大缩短。74例患儿使用Peg-asp、Ecoli-asp发生过敏或者沉默失活后,换用Erw-asp均能获得有效酶活性;国产Erw-asp肌注后的活性半衰期明显长于国外文献报道(23. 1±2. 5h vs. 15. 6±3. 1h)。结论 Peg-asp推荐给药剂量2000u/m^2,推荐给药间隔3周一次;Peg-asp治疗中,可能会发生沉默失活,需要警惕;Peg-asp与Ecoli-asp存在交叉免疫原性,对一种过敏后不宜简单更换为另一种;Erw-asp作为二线用药能在Peg-asp、Ecoli-asp过敏或沉默失活后获得有效活性,依据药代动力学,国产制剂推荐剂量为20000u/m^2,每周2次。 Objective To study the pharmacokinetics of Peg-asparaginase( Peg-asp) and Erwasparaginase( Erw-asp) in patients of normal,allergy and silent inactivation by testing the activity of asparaginase,and guide clinical medication. Methods Test the activity of asparaginase on D8、D15 and D22 after one dose of Peg-asp and on 24 h、48 h、72 h and 96 h after one dose of Erw-asp,respectively.Results 957 samples from 206 patients of acute lymphoblastic leukemia were tested for asparaginase activity. Among them 66 patients after one dose of Peg-asp( 2000 u/m^2),65 patients could get a nadir serum asparaginase activity( NSAA) > 100 IU/L for 3 weeks. The incidence of silent inactivation for Pegasp is 5%. The activity half-life of Peg-asp significantly reduced in 26 patients who were allergy to EcoliAsparaginase( Ecoli-asp). 74 patients who showed allergy or silent inactivation to Peg-asp were then switched to Erw-asp and all of them can maintain NSAA≥100 IU/L. Interestingly,we observed that the activity half-life of domestic Erw-asp was longer than that of foreign products reported in literature( 23. 1 ± 2. 5 h vs. 15. 6 ± 3. 1 h). Conclusions Peg-asp could be given by 2000 u/m^2 every three weeks and we should pay more attention to silent inactivation. In addition,due to Ecoli-asp derived Peg-asp have cross-reactivity with regular Ecoli-asp,it is not reasonable to switch each other after allergy was found to either of them. In this circumstance,Erw-asp should be an appropriate second-line treatment,and can obtain effective activity after Peg-asp,Ecoli-asp allergy or silent inactivation. Finally,according to the pharmacokinetics,we commend that intramuscular administration of domestic Erw-asp can be given by 20000 IU/m^2 twice a week.

作者陈长城周敏沈树红吴娟黄诗颖张顺国 CHEN Changcheng;ZHOU Min;SHEN Shuhong;WU Juan;HUANG Shiying;ZHANG Shunguo(Department of Hematology and Oncology,Shanghai Children's Medical Center of Shanghai Jiaotong University,Shanghai 200127,China)

机构地区上海交通大学医学院附属上海儿童医学中心血液肿瘤科

出处《中国小儿血液与肿瘤杂志》 CAS 2020年第1期9-13,共5页 Journal of China Pediatric Blood and Cancer

基金上海市卫生和计划生育委员会科研课题《门冬酰胺酶活性相关特异性抗体研究》.

关键词门冬酰胺酶活性儿童急性淋巴细胞性白血病药代动力学 Asparaginase activity Children Acute lymphoblastic leukemia Pharmacokinetics

分类号 R969.1 [医药卫生—药理学]

作者简介通讯作者:沈树红,Email:shenshuhong@scmc.com.cn

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参考文献1

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