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二肽基肽酶-4(DPP-4)抑制剂引起的大疱性类天疱疮:通过 vigibase® 分析进行药物警戒-药效学/药代动力学评估。

Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors: a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®.

机构信息

Unit of Clinical Pharmacology Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano , Milan , Italy.

Department of Diagnostics and Public Health, Section of Pharmacology, University of Verona , Verona , Italy.

出版信息

Expert Opin Drug Saf. 2019 Nov;18(11):1099-1108. doi: 10.1080/14740338.2019.1668373. Epub 2019 Sep 26.

Abstract

: To examine the signals of bullous pemphigoid (BP) with dipeptidyl peptidase-4 inhibitors (DPP-4i) in VigiBase® and the potential role of their pharmacodynamic/pharmacokinetic parameters in the occurrence of BP. : Case/non-case analyses were performed in VigiBase® to examine the signal of BP [reporting odds ratio (ROR)] for gliptins. Secondly, the authors performed linear regression analyses to explore the association between DPP-4i signals for BP and their affinities toward different target enzymes (DPP-2, DPP-4, DPP-8, and DPP-9) and their volume of distribution (Vd). : A significant BP signal was found for DPP-4i. The ROR for pooled DPP-4i was 179.48 (95% CI: 166.41-193.58). The highest ROR was found for teneligliptin 975.04 (801.70-1185.87) and lowest for saxagliptin 18.9 (11.5-30.9). Linear regression analyses showed a considerable trend to significance for the linear correlation between the BP signal and gliptin affinity at DPP-4 (slope = 1.316 [-0.4385-3.21], p = 0.067, R = 0.40) but not the other enzyme targets, nor for Vd. : The findings suggest a clinical relevance of gliptins selectivity for DDP-4 in the development of BP as a result of exposure to these drugs. Future preclinical and clinical studies are needed for a better understanding of this correlation.

摘要

目的

在 VigiBase® 中检测二肽基肽酶-4 抑制剂(DPP-4i)相关的大疱性类天疱疮(BP)信号,并探讨其药效学/药代动力学参数在 BP 发生中的潜在作用。

方法

在 VigiBase® 中进行病例对照分析,以评估 DPP-4i 治疗 BP 的信号[报告比值比(ROR)]。其次,作者进行线性回归分析,以探讨 DPP-4i 治疗 BP 的信号与它们对不同靶酶(DPP-2、DPP-4、DPP-8 和 DPP-9)亲和力以及分布容积(Vd)之间的关联。

结果

发现 DPP-4i 与 BP 信号显著相关。DPP-4i 的汇总 ROR 为 179.48(95%CI:166.41-193.58)。其中,替格列汀的 ROR 最高(975.04,801.70-1185.87),而沙格列汀的 ROR 最低(18.9,11.5-30.9)。线性回归分析显示,BP 信号与 DPP-4 亲和力之间存在显著的线性相关趋势(斜率=1.316[-0.4385-3.21],p=0.067,R=0.40),但与其他靶酶的亲和力或 Vd 无关。

结论

研究结果提示 DPP-4i 对 DPP-4 的选择性可能与这些药物暴露相关的 BP 发生有关,这提示 DPP-4i 可能具有临床相关性。未来需要进行更多的临床前和临床研究,以更好地理解这种相关性。

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