Knebel William, Palmen Mary, Dowell James A, Gastonguay Marc
Metrum Research Group LLC, Tariffville, CT 06081, USA.
J Clin Pharmacol. 2008 Jul;48(7):837-48. doi: 10.1177/0091270008318218. Epub 2008 May 19.
This analysis quantifies the population pharmacokinetics of subcutaneous and intravenous epoetin delta, an epoetin produced in a human cell line, in pediatric patients with chronic kidney disease and estimates the effects of covariate factors on epoetin delta and epoetin alfa pharmacokinetic parameters. Erythropoietin serum concentration data, taken from a phase III study conducted in 60 patients aged 1 to 17 years, were best described by a 1-compartment model with first-order absorption and elimination. The typical point estimates were clearance (0.268 L/h), central volume of distribution (1.03 L), absorption rate constant (0.0554 h(-1)), and bioavailability (0.708) for a 35-kg male < or = 10 years who was predialysis and on subcutaneous epoetin delta treatment. Erythropoietin pharmacokinetic parameters were similar in pediatric patients as compared with adults when scaled by weight. The subcutaneous administration of epoetin alfa exhibited lower systemic bioavailability than subcutaneous administration of epoetin delta.
本分析量化了皮下和静脉注射人细胞系生产的促红细胞生成素δ在慢性肾病儿科患者中的群体药代动力学，并估计协变量因素对促红细胞生成素δ和促红细胞生成素α药代动力学参数的影响。促红细胞生成素血清浓度数据取自一项在60名1至17岁患者中进行的III期研究，用具有一级吸收和消除的单室模型能最好地描述这些数据。对于一名体重35千克、年龄≤10岁、未透析且接受皮下促红细胞生成素δ治疗的男性，典型的点估计值为清除率（0.268升/小时）、中央分布容积（1.03升）、吸收速率常数（0.0554小时⁻¹）和生物利用度（0.708）。按体重标化后，儿科患者的促红细胞生成素药代动力学参数与成人相似。与皮下注射促红细胞生成素δ相比，皮下注射促红细胞生成素α的全身生物利用度较低。
