新型长效聚乙二醇干扰素 alfa-2b 在健康中国受试者中的药代动力学和药效学。
Pharmacokinetics and Pharmacodynamics of Novel Long-Acting Ropeginterferon Alfa-2b in Healthy Chinese Subjects.
机构信息
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, No. 252, Wuxing Street, Xinyi District, Taipei City, 110301, Taiwan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, No. 252, Wuxing Street, Xinyi District, Taipei City, 110301, Taiwan.
出版信息
Adv Ther. 2021 Sep;38(9):4756-4770. doi: 10.1007/s12325-021-01863-y. Epub 2021 Jul 30.
INTRODUCTION
Ropeginterferon alfa-2b is a novel mono-pegylated human recombinant interferon (IFN) with the addition of N-terminal proline covalently attached by a 40-kDa polyethylene (peg) moiety. The present study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) profiles and safety of the product in healthy Chinese.
METHODS
Forty subjects were enrolled and treated with a single subcutaneous injection of either 180 mcg peg-IFN alfa-2a or 90, 180, and 270 mcg ropeginterferon alfa-2b.
RESULTS
The mean T of ropeginterferon alfa-2b was 92-141 h and the elimination half-life was 78-129 h. Dose-related, non-proportional increase in ropeginterferon alfa-2b exposure was observed, which was higher than for peg-IFN alfa-2a. The PD parameters were similar between each dose level of ropeginterferon alfa-2b. The mean T of β-microglobulin ranged from 118 to 132 h after a single dose of ropeginterferon alfa-2b. The average E was 3 mcg/ml in all dose levels and the mean AUEC ranged from 1608 to 1775 h/mcg/ml. The TEAEs were comparable among each treatment group and no death nor drug-related SAE was reported.
CONCLUSION
Ropeginterferon alfa-2b is safe and well tolerated after a single subcutaneous injection up to 270 mcg in healthy Chinese.
CLINICAL TRIAL REGISTRATION
www.chinadrugtrials.org.cn , CTR20190451.
简介
罗哌干扰素 alfa-2b 是一种新型的单聚乙二醇化人重组干扰素（IFN），其 N 端脯氨酸通过 40 kDa 聚乙二醇（peg）部分共价连接。本研究旨在评估该产品在健康中国人体内的药代动力学（PK）、药效学（PD）特征和安全性。
方法
共招募 40 名受试者，分别单次皮下注射 180 mcg 聚乙二醇干扰素 alfa-2a 或 90、180 和 270 mcg 罗哌干扰素 alfa-2b。
结果
罗哌干扰素 alfa-2b 的平均 T 为 92-141 h，消除半衰期为 78-129 h。观察到罗哌干扰素 alfa-2b 暴露量呈剂量相关、非比例增加，高于聚乙二醇干扰素 alfa-2a。罗哌干扰素 alfa-2b 各剂量水平的 PD 参数相似。单次给药后，β-微球蛋白的平均 T 范围为 118-132 h。所有剂量水平的平均 E 为 3 mcg/ml，平均 AUEC 范围为 1608-1775 h/mcg/ml。各治疗组的 TEAEs 相似，无死亡或药物相关严重不良事件报告。
结论
在中国健康受试者中，单次皮下注射罗哌干扰素 alfa-2b 剂量高达 270 mcg 是安全且耐受良好的。
临床试验注册
www.chinadrugtrials.org.cn ， CTR20190451。
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