PEGylated versus non-PEGylated drugs: A cross-sectional analysis of adverse events in the FDA Adverse Event Reporting System (FAERS) Database

被引：3

作者：

Zhu, Zhengyi ^{[1
]}

Gao, Peng ^{[1
]}

Hu, Yan ^{[1
]}

Wang, Junyan ^{[1
]}

Wang, Huijuan ^{[1
]}

Yang, Jufei ^{[1
]}

Huang, Lingfei ^{[1
]}

Ji, Cai ^{[1
]}

Ni, Yinghua ^{[1
]}

Fang, Luo ^{[1
]}

机构：

[1] Zhejiang Univ, Childrens Hosp, Dept Pharm, Sch Med,Natl Clin Res Ctr Child Hlth, Hangzhou, Zhejiang, Peoples R China

来源：

INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS | 2020年 / 58卷 / 06期

基金：

中国国家自然科学基金;

关键词：

PEGylation; adverse event; FDA Adverse Event Reporting System; pharmacovigilance; ANTI-PEG ANTIBODIES; SIGNAL-DETECTION; DISPROPORTIONALITY; ASPARAGINASE; BIOPHARMACEUTICALS; PHARMACOKINETICS; METABOLISM; EXPERIENCE; POLYMER; SAFETY;

D O I：

10.5414/CP203735

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Objective: PEGylation is commonly used to optimize pharmacological properties and improve the clinical response of drugs. Due to the inherent toxicity of polyethylene glycol (PEG) and pharmacological changes induced by PEGylation. the safety may be altered and required to be explored. This study explored the adverse events (AEs) associated with PEGylation by comparing pharmacovigilance data of PEGylated and parent drugs. Materials and methods: We conducted a disproportionality analysis of spontaneous reports associated with PEGylated and corresponding parent medications from the FDA Adverse Event Reporting System database recorded between the 1st quarter of 2004 and the 4th quarter of 2018 at the level of preferred terms (PTs) and standard MedDRA queries (SMQs), respectively. The AEs probably different in risk due to changed pharmacological effects and inherent toxicity of PEG were analyzed. Results: A total of 259,428 cases associated to six drug pairs (filgrastim, asparaginase, interferon alpha-2a, interferon alpha-2b,interferon beta-1a and liposomal doxoru- bicin) were collected. Although 95% of PTs were comparable between the two groups, PTs of deep vein thrombosis. pancreatitis acute, diabetes mellitus, liver disorder, disorientation, aphasia and infection, and SMQ of embolic and thrombotic events were significantly alleviated by PEGylation. No PT was significantly enhanced by PEGylation. con-, clusion: The pharmacovigilance profiles of PEGylated and non-PEGylated agents were similar. Further clinical assessment is required to validate the pharmacovigilance data. What is known about this subject - PEGylation is commonly used to optimize pharmaceutical properties. The effectiveness of PEGylated agents was superior to conventional agents. On the other hand, the toxicity of agents may probably be altered by PEGylation as the pharmacological profile changed. and the immunogenicity of polyethylene glycol (PEG) may also have negative effects. What this study adds - The adverse event profiles of PEGylated and non-PEGylated agents were similar. - No adverse event was significantly enhanced by PEGylation. - The embolic and thrombotic events were alleviated by PEGylation.

引用

页码：332 / 342

页数：11

共 42 条

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