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聚乙二醇干扰素的药代动力学

Pharmacokinetics of peginterferons.

作者信息

Zeuzem Stefan, Welsch Christoph, Herrmann Eva

机构信息

Department of Medicine, Division of Gastroenterology, Hepatology, and Endocrinology, Saarland University Hospital, Homburg/Saar, Germany.

出版信息

Semin Liver Dis. 2003;23 Suppl 1:23-8. doi: 10.1055/s-2003-41631.

Abstract

Two polyethylene glycol (PEG)-modified interferons are approved for the treatment of chronic hepatitis C. The pharmocokinetic properties of the branched 40 kDa pegylated interferon alfa-2a differ from the linear 12 kDa pegylated interferon alfa-2b. The absorption half-life of standard interferon alfa is 2.3 hours, while absorption half-lives for peginterferon alfa-2a and alfa-2b are 50 hours and 4.6 hours, respectively. The volume of distribution for peginterferon alfa-2a is considerably restricted, while the volume of distribution for peginterferon alfa-2b is only approximately 30% lower than that for conventional interferon. Because of its large size, the 40 kD peginterferon alfa-2a has a more than 100-fold reduction in renal clearance compared with conventional interferon alfa. Clearance of peginterferon alfa-2b is about one-tenth that of unmodified interferon alfa. Although data are limited, both drugs appear to show differences in the initial viral decay pattern in patients with chronic hepatitis C. However, it remains unknown whether these differences in the initial viral decline predict differences in the primary clinical endpoint, sustained virological response.

摘要

两种聚乙二醇(PEG)修饰的干扰素已被批准用于治疗慢性丙型肝炎。分支状40 kDa聚乙二醇化干扰素α-2a的药代动力学特性与线性12 kDa聚乙二醇化干扰素α-2b不同。标准干扰素α的吸收半衰期为2.3小时,而聚乙二醇化干扰素α-2a和α-2b的吸收半衰期分别为50小时和4.6小时。聚乙二醇化干扰素α-2a的分布容积受到很大限制,而聚乙二醇化干扰素α-2b的分布容积仅比传统干扰素低约30%。由于其分子量大,40 kD聚乙二醇化干扰素α-2a的肾清除率比传统干扰素α降低了100多倍。聚乙二醇化干扰素α-2b的清除率约为未修饰干扰素α的十分之一。虽然数据有限,但这两种药物在慢性丙型肝炎患者的初始病毒衰减模式上似乎都存在差异。然而,这些初始病毒下降的差异是否预示着主要临床终点(持续病毒学应答)的差异仍不清楚。

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