促红细胞生成素治疗缺氧缺血性脑病新生儿的药代动力学变化

目的通过测定缺氧缺血性脑病（HIE）新生儿用药前后血清、脑脊液（CSF）促红细胞生成素（EPO）水平,探讨EPO的药代动力学变化及透过患儿血脑脊液屏障的情况。方法对35例48 h内收入院的中、重度HIE患儿随机分为用药前组10例,观察组25例。入院后观察组立即予重组人促红细胞生成素（rhEPO）500 U/kg皮下注射。其中用药后3 h组10例,8 h组8例,24 h组7例。用药前组在常规治疗前,观察组在给予EPO后的各时间点分别抽取静脉血、CSF,采用放射免疫法测定血清、CSF中EPO水平。结果观察组血清EPO水平3 h达峰值,是用药前的2.6倍（P〈0.01）,用药后24 h仍高于用药前水平,但无显著性差异。CSF中EPO水平也在用药后3 h达高峰（P〈0.05）,但在用药后8 h回落至用药前水平。观察组用药后3 h血清与CSF中EPO水平呈直线相关（r=0.69 P〈0.05）,而其他组间未发现相关性。结论EPO能通过HIE患儿的血脑脊液屏障,CSF中EPO水平与血液EPO水平有关。

Changes of Pharmacokinetics of Erythropoietin in Neonate with Hypoxic-Ischemic Encephalopathy

Objective To explore the pharmacokinetics and possibility to pass through the blood brain barrier of the recombinant human erythropoietin(EPO) in neonate with hypoxic-ischemic encephalopathy(HIE) by measuring the erythropoietin concentration in blood and cerebrospinal fluid(CSF).Methods Moderate and severe HIE infants were randomized to pre-treatment group(n=10) and treatment group of 3 h(n=10),8 h(n=8) and 24 h(n=7)after a single subcutaneous EPO administration with a dose of 500 U/kg.The EPO concentration in blood and CSF were measured by imunoradioassay.Results The EPO concentration in blood reached peak at 3 h after treatment,which was 2.6 times higher than that in before treatment patients(P<0.01).It decreased after that and still kept high level at 24 h after EPO administration even though no significant differentce.The EPO concentration in CSF had a similar tendency with that in blood and reached peak at 3 h post EPO injection,which was significantly higher than that in patients of before treatment(P<0.05),but it recovered at 8 h.Regression analysis showed that EPO concentration in blood and CSF was positively correlated at 3 h after EPO administration(r=0.69 P<0.05).But other groups had no correlations.Conclusions EPO can pass through the blood brain barrier in HIE infants.The EPO concentration in CSF is correlated with EPO concentration in blood.