Darbepoetin administration to neonates undergoing cooling for encephalopathy: a safety and pharmacokinetic trial.
Darbepoetin administration to neonates undergoing cooling for encephalopathy: a safety and pharmacokinetic trial.
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达贝泊汀对因脑病而接受降温的新生儿进行给药：一项安全性和药代动力学试验。
DOI：
10.1038/pr.2015.101
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发表时间：
2015-09
影响因子：
3.6
通讯作者：
Yoder BA
中科院分区：
文献类型：
--
作者：
Baserga MC;Beachy JC;Roberts JK;Ward RM;DiGeronimo RJ;Walsh WF;Ohls RK;Anderson J;Mayock DE;Juul SE;Christensen RD;Loertscher MC;Stockmann C;Sherwin CM;Spigarelli MG;Yoder BA
尽管有治疗性低温，新生儿脑病（NE）有很高的死亡率或残疾。Darbepopoietin alfa（Darbe）具有与促红细胞生成素相当的生物活性，但延长了循环半衰期（t1/2）。我们的目的是确定Darbe的安全性和药代动力学作为体温过低的连续治疗。将30例（n = 10/组）妊娠≥ 36周接受NE低温治疗的婴儿随机分为安慰剂组、低剂量（2 μg/kg）组和高剂量（10 μg/kg）组。记录1个月的不良事件。获得血清样品以表征Darbe药代动力学。不良事件（低血压、肝肾功能改变、癫痫发作和死亡）与安慰剂和历史对照相似。在以2和10 μg/kg剂量首次给予Darbe后，t1/2分别为24和32 h，曲线下面积（AUCinf）分别为26，555和180，886 h*mU/ml*。此外，剂量（0.05和0.04 l/h）之间的清除率无显著差异。在第7天，t1/2分别为26和35 h，AUCinf分别为10，790和56，233 h*mU/ml*（*P < 0.01）。达贝联合低温与安慰剂具有相似的安全性特征，药代动力学足以每周给药。
Despite therapeutic hypothermia, neonates with encephalopathy (NE) have high rates of death or disability. Darbepoetin alfa (Darbe) has comparable biological activity to erythropoietin, but has extended circulating half-life (t1/2). Our aim was to determine Darbe safety and pharmacokinetics as adjunctive therapy to hypothermia. Thirty infants (n = 10/arm) ≥36wk gestation undergoing therapeutic hypothermia for NE were randomized to receive placebo, Darbe low dose (2 μg/kg), or high dose (10 μg/kg) given intravenously within 12 h of birth (first dose/hypothermia condition) and at 7 d (second dose/normothermia condition). Adverse events were documented for 1 mo. Serum samples were obtained to characterize Darbe pharmacokinetics. Adverse events (hypotension, altered liver and renal function, seizures, and death) were similar to placebo and historical controls. Following the first Darbe dose at 2 and 10 μg/kg, t1/2 was 24 and 32 h, and the area under the curve (AUCinf) was 26,555 and 180,886 h*mU/ml*, respectively. In addition, clearance was not significantly different between the doses (0.05 and 0.04 l/h). At 7 d, t1/2 was 26 and 35 h, and AUCinf was 10,790 and 56,233 h*mU/ml*, respectively (*P < 0.01). Darbe combined with hypothermia has similar safety profile to placebo with pharmacokinetics sufficient for weekly administration.
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影响因子：
5
作者：
Banks, WA;Jumbe, NL;Heatherington, AC
通讯作者：
Heatherington, AC
影响因子：
4.8
作者：
Grasso, Giovanni;Graziano, Francesca;Iacopino, Domenico Gerardo
通讯作者：
Iacopino, Domenico Gerardo
影响因子：
2.5
作者：
SHANKARAN, S;WOLDT, E;NANDYAL, R
通讯作者：
NANDYAL, R
影响因子：
2.9
作者：
Warwood, T. L.;Ohls, R. K.;Christensen, R. D.
通讯作者：
Christensen, R. D.
影响因子：
3.7
作者：
Freise, Kevin. J.;Widness, John A.;Veng-Pedersen, Peter
通讯作者：
Veng-Pedersen, Peter