罗氏干扰素 Alfa-2b 治疗丙型肝炎的治疗剂量及其药代动力学。

A therapeutic dose and its pharmacokinetics of ropeginterferon Alfa-2b for hepatitis C treatment.

机构信息

Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan.

Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

出版信息

J Formos Med Assoc. 2024 Jan;123(1):55-61. doi: 10.1016/j.jfma.2023.08.023. Epub 2023 Sep 2.

DOI:10.1016/j.jfma.2023.08.023

PMID:37666718

Abstract

AIM

Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. Its biweekly dosing schema has demonstrated tolerability and clinical efficacy for treating chronic hepatitis in previous clinical studies. This trial evaluates the pharmacokinetics of 400 μg ropeginterferon alfa-2b in patients with chronic hepatitis C virus (HCV) and provides the data to support the clinical utility of ropeginterferon alfa-2b at 400 μg.

METHODS

Seventeen patients with chronic HCV genotype 2 were enrolled to receive a single injection of 400 μg ropeginterferon alfa-2b plus 14-day treatment of ribavirin. Pharmacokinetics, safety, and HCV RNA reduction/clearance were assessed.

RESULTS

T was 154.003 h and T was 114.273 h. The C was 29.823 ng mL. AUC was 9364.292 h∗ng mL and AUC was 11084.317 h∗ng mL. All adverse events were mild or moderate, and there were no serious adverse events. A 1000-fold reduction in the geometric mean of HCV RNA was observed 14 d after the single injection of ropeginterferon alfa-2b. Two patients achieved clearance of HCV RNA, and the other five patients had HCV RNA levels lower than 200 IU mL.

CONCLUSION

Ropeginterferon alfa-2b at 400 μg led to PK exposures associated with safety and notable clinical activity in patients with chronic HCV. This study suggests that ropeginterferon alfa-2b at 400 μg is an acceptable dosing regimen for treating chronic HCV and also provides supporting data for the clinical use of ropeginterferon alfa-2b at a higher starting dose for other indications.

摘要

目的

罗匹尼罗干扰素 alfa-2b 是一种新型单聚乙二醇化脯氨酸干扰素。在之前的临床研究中，其双周给药方案已被证明可耐受且对慢性丙型肝炎（HCV）具有临床疗效。本试验评估了 400μg 罗匹尼罗干扰素 alfa-2b 在慢性 HCV 病毒（HCV）患者中的药代动力学，并提供了支持罗匹尼罗干扰素 alfa-2b 以 400μg 起始剂量用于其他适应证的临床应用的数据。

方法

17 例慢性 HCV 基因型 2 患者接受单剂量 400μg 罗匹尼罗干扰素 alfa-2b 加 14 天利巴韦林治疗。评估药代动力学、安全性和 HCV RNA 降低/清除情况。

结果

T1/2 为 154.003 h，T1/2 为 114.273 h。Cmax 为 29.823ng/mL，AUC0-t 为 9364.292 h·ng/mL，AUC0-∞ 为 11084.317 h·ng/mL。所有不良事件均为轻度或中度，无严重不良事件。单次注射罗匹尼罗干扰素 alfa-2b 14 天后，HCV RNA 的几何均数降低了 1000 倍。2 例患者实现了 HCV RNA 的清除，其余 5 例患者的 HCV RNA 水平低于 200IU/mL。

结论

400μg 罗匹尼罗干扰素 alfa-2b 导致了与安全性相关的 PK 暴露，并在慢性 HCV 患者中产生了显著的临床疗效。本研究表明，400μg 罗匹尼罗干扰素 alfa-2b 是治疗慢性 HCV 的一种可接受的给药方案，也为罗匹尼罗干扰素 alfa-2b 用于其他适应证的更高起始剂量的临床应用提供了支持数据。