Lerner Gary, Kale Arundhati S, Warady Bradley A, Jabs Kathy, Bunchman Timothy E, Heatherington Anne, Olson Kurt, Messer-Mann Louise, Maroni Bradley J
Division of Nephrology, Children's Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA.
Pediatr Nephrol. 2002 Nov;17(11):933-7. doi: 10.1007/s00467-002-0932-0. Epub 2002 Sep 14.
Darbepoetin alfa is a novel erythropoiesis-stimulating protein with a two- to threefold longer half-life than recombinant human erythropoietin (epoetin) in adult patients with chronic kidney disease (CKD). This randomized, open-label, crossover study was conducted to determine the pharmacokinetic profile of darbepoetin alfa in pediatric patients with CKD. Twelve patients 3-16 years of age with CKD were randomized and received a single 0.5 micro g/kg dose of darbepoetin alfa administered intravenously (IV) or subcutaneously (SC). After a 14- to 16-day washout period, patients received an identical dose of darbepoetin alfa by the alternate route. After IV administration, the mean clearance of darbepoetin alfa was 2.3 ml/h per kg, with a mean terminal half-life of 22.1 h. After SC administration, absorption was rate limiting, with a mean terminal half-life of 42.8 h and a mean bioavailability of 54%. Comparison of these results with those from a previous study of darbepoetin alfa in adult patients indicated that the disposition of darbepoetin alfa administered IV or SC is similar in adult and pediatric patients, although absorption may be slightly more rapid in pediatric patients after SC dosing. The mean terminal half-life of darbepoetin alfa in this study was approximately two- to fourfold longer than that previously reported for epoetin in pediatric patients.
达贝泊汀α是一种新型促红细胞生成蛋白，在成年慢性肾脏病（CKD）患者中，其半衰期比重组人促红细胞生成素（促红细胞生成素）长2至3倍。本随机、开放标签、交叉研究旨在确定达贝泊汀α在儿童CKD患者中的药代动力学特征。12名3至16岁的CKD患儿被随机分组，接受单次0.5μg/kg剂量的达贝泊汀α静脉注射（IV）或皮下注射（SC）。在14至16天的洗脱期后，患者通过另一种途径接受相同剂量的达贝泊汀α。静脉注射后，达贝泊汀α的平均清除率为每千克2.3ml/h，平均终末半衰期为22.1小时。皮下注射后，吸收是限速的，平均终末半衰期为42.8小时，平均生物利用度为54%。将这些结果与先前一项关于达贝泊汀α在成年患者中的研究结果进行比较表明，静脉注射或皮下注射达贝泊汀α在成年和儿童患者中的处置情况相似，尽管儿童患者皮下给药后吸收可能稍快。本研究中达贝泊汀α的平均终末半衰期比先前报道的儿童促红细胞生成素的半衰期长约2至4倍。
