Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-ro, Seoul 110-744, Korea.
BioDrugs. 2013 Apr;27(2):149-58. doi: 10.1007/s40259-013-0010-0.
HM10460A is a newly developed recombinant human granulocyte colony-stimulating factor with long-lasting characteristics. This factor is expected to be used for chemotherapy-related neutropenic conditions.
The aim of the present study was to evaluate the pharmacokinetics and pharmacodynamics of HM10460A following subcutaneous administration to healthy Korean subjects.
A randomized, double-blind, placebo-controlled, escalating single-dose study was conducted in 40 healthy Korean subjects. The subjects were allocated to single-dose groups of 5, 15, 45, 135 or 350 μg/kg, or placebo. Serial blood samples for pharmacokinetic/pharmacodynamic analyses were collected up to 22 days, and urine samples for pharmacokinetic analysis were collected up to 3 days after subcutaneous administration of HM10460A. The serum and urine concentrations were analyzed by enzyme-linked immunosorbent assay.
Most of the serum concentrations in the 5 and 15 μg/kg dosing groups were below the lower limit of quantification (LLOQ). The median times to the peak concentration (T(max)) of HM10460A in the 45, 135, and 350 μg/kg dosing groups were 8.0, 14.0, and 24.0 h, respectively. The mean ± standard deviation values of the dose-normalized maximum concentration (C(max)) and dose-normalized area under the concentration-time curve (AUC(last)) for the 45, 135, and 350 μg/kg dosing groups were 14.13 ± 6.37, 66.19 ± 38.71, and 34.65 ± 19.69 μg/L/mg, respectively, and 265.0 ± 124.1, 2144 ± 1232, and 1386 ± 701.2 μg h/L/mg, respectively. The concentrations of HM10460A in the urine were below the LLOQ in all of the subjects. In all of the dosing groups, the area under the effect-time curve (AUEC(last)) of both the absolute neutrophil count (ANC) and the CD34(+) cell count increased as the dose increased.
HM10460A showed dose-dependent pharmacokinetic characteristics, and the systemic exposure of HM10460A was positively correlated with the ANC and CD34(+) cell counts.
HM10460A 是一种新开发的具有长效特征的重组人粒细胞集落刺激因子。该因子有望用于化疗相关的中性粒细胞减少症。
本研究旨在评估 HM10460A 经皮下给药于健康韩国受试者后的药代动力学和药效学。
进行了一项随机、双盲、安慰剂对照、递增单剂量研究，共纳入 40 名健康韩国受试者。受试者按 5、15、45、135 或 350μg/kg 单剂量或安慰剂进行分组。给药后，受试者在 22 天内进行了多次血样采集，用于药代动力学/药效学分析；在 3 天内进行了多次尿样采集，用于药代动力学分析。血清和尿液浓度采用酶联免疫吸附试验进行分析。
5μg/kg 和 15μg/kg 剂量组的大多数血清浓度低于定量下限（LLOQ）。45μg/kg、135μg/kg 和 350μg/kg 剂量组 HM10460A 的中位达峰时间（T(max))分别为 8.0、14.0 和 24.0 小时。45μg/kg、135μg/kg 和 350μg/kg 剂量组的剂量归一化最大浓度（C(max))和剂量归一化浓度-时间曲线下面积（AUC(last))的均值±标准差分别为 14.13±6.37、66.19±38.71 和 34.65±19.69μg/L/mg，265.0±124.1、2144±1232 和 1386±701.2μg h/L/mg。所有受试者的 HM10460A 尿液浓度均低于 LLOQ。在所有剂量组中，绝对中性粒细胞计数（ANC）和 CD34(+)细胞计数的效应时间曲线下面积（AUEC(last))均随剂量增加而增加。
HM10460A 呈现出剂量依赖性的药代动力学特征，HM10460A 的全身暴露与 ANC 和 CD34(+)细胞计数呈正相关。
