SGLT2 inhibitors may increase creatinine clearance: data mining utilizing the FDA Adverse Event Report System database and pharmacokinetic study with rats.

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Pharmacology Pub Date : 2025-06-25 DOI:10.1159/000546838
Yuichi Uwai, Tomohiro Nabekura
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引用次数: 0

Abstract

Introduction: Augmented renal clearance is a condition in which creatinine clearance exceeds 130 ml/min/1.73 m². The present study aimed to identify drugs that increase creatinine clearance.

Methods: We initially investigated drugs associated with an upsurge in the reporting frequencies of "creatinine renal clearance increased" (CRCI) and "glomerular filtration rate increased" (GFRI) using the FDA Adverse Event Reporting System (FAERS) database. Effect of the drugs on renal clearance of creatinine and lithium was examined using rats.

Results: The database contained 625 reports on CRCI and GFRI. Among the primary suspect drugs identified, empagliflozin had the highest number of reports (29), followed by canagliflozin (27), emtricitabine/tenofovir (21), and sacubitril/valsartan (21). Dapagliflozin had 16 reports. Reporting odds ratios (95% confidence intervals) for empagliflozin, canagliflozin, and dapagliflozin were 29.7 (20.5-43.1), 28.6 (19.5-42.1), and 19.7 (12.0-32.3), respectively. In rats infused with phlorizin, a typical inhibitor of sodium-glucose cotransporters (SGLTs), increases were observed in fractional glucose excretion, creatinine clearance, and the renal clearance of lithium. The plasma concentration of creatinine remained unchanged, while that of lithium decreased. Renal glucose excretion in rats administered phlorizin correlated with creatinine clearance (r = 0.859).

Conclusion: These results suggest that SGLT2 inhibitors may increase renal clearance of creatinine or drugs.

SGLT2抑制剂可能增加肌酐清除率:利用FDA不良事件报告系统数据库和大鼠药代动力学研究的数据挖掘。
肾清除率增强是指肌酐清除率超过130 ml/min/1.73 m²。目前的研究旨在确定增加肌酐清除率的药物。方法:我们使用FDA不良事件报告系统(FAERS)数据库,初步调查了与“肌酐肾清除率增加”(CRCI)和“肾小球滤过率增加”(GFRI)报告频率激增相关的药物。以大鼠为实验对象,观察药物对肾清除肌酐和锂的影响。结果:数据库共收录CRCI和GFRI报告625份。在确定的主要可疑药物中,恩格列净报告最多(29例),其次是卡格列净(27例)、恩曲他滨/替诺福韦(21例)和苏比利/缬沙坦(21例)。达格列净有16例报告。恩格列净、卡格列净和达格列净的报告优势比(95%可信区间)分别为29.7(20.5-43.1)、28.6(19.5-42.1)和19.7(12.0-32.3)。在大鼠中,注射了一种典型的钠-葡萄糖共转运体(SGLTs)抑制剂苯丙素,观察到分数葡萄糖排泄,肌酐清除率和锂的肾清除率增加。血浆肌酐浓度保持不变,而锂浓度下降。给药的大鼠肾葡萄糖排泄与肌酐清除率相关(r = 0.859)。结论:SGLT2抑制剂可能增加肌酐或药物的肾清除率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pharmacology
Pharmacology 医学-药学
CiteScore
5.60
自引率
0.00%
发文量
52
审稿时长
6-12 weeks
期刊介绍: ''Pharmacology'' is an international forum to present and discuss current perspectives in drug research. The journal communicates research in basic and clinical pharmacology and related fields. It covers biochemical pharmacology, molecular pharmacology, immunopharmacology, drug metabolism, pharmacogenetics, analytical toxicology, neuropsychopharmacology, pharmacokinetics and clinical pharmacology. In addition to original papers and short communications of investigative findings and pharmacological profiles the journal contains reviews, comments and perspective notes; research communications of novel therapeutic agents are encouraged.
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