Acidifying agents impact erlotinib and gefitinib pharmacokinetic parameters and elevate liver enzymes in Wistar rats.

IF 3.4 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Amsha S Alsegiani, Aliyah Almomen, Maria Arafah, Nourah Z Alzoman, Abdullah K Alshememry
{"title":"Acidifying agents impact erlotinib and gefitinib pharmacokinetic parameters and elevate liver enzymes in Wistar rats.","authors":"Amsha S Alsegiani, Aliyah Almomen, Maria Arafah, Nourah Z Alzoman, Abdullah K Alshememry","doi":"10.1007/s44446-025-00032-4","DOIUrl":null,"url":null,"abstract":"<p><p>Erlotinib (ERL) and Gefitinib (GEF) are weakly basic drugs with pH-dependent solubility profiles mainly dependent on stomach pH. We proposed possible drug and/or food-drug interactions with acidifying agents. Citric acid (CA) and phosphoric acid (PPA) are the most common acidifying agents used in food and medication to treat certain conditions. This study evaluated the impact of concomitant consumption of CA and PA on ERL and GEF pharmacokinetic parameters (PKs). The PKs of ERL and GEF were investigated in rats after four weeks of CA and PPA consumption in low (175 mg/kg) and high (100 mg/kg) doses using UPLC-MS/MS. Data indicated that acidifying agents altered PKs of ERL and GEF dose-dependently. High doses of CA and PPA significantly increased the Cmax of ERL by 103% and 218%, the AUC<sub>0-72</sub> by 35% and 78%, respectively, while reducing CL/F by 44% with CA and 74% with PPA. For GEF, Low and high doses of PPA increased C<sub>max</sub> and T<sub>max</sub> with a reduction of CL/F. A low dose of CA did not impact C<sub>max</sub>, significantly decreased AUC<sub>0-72</sub> (28%), and increased CL/F (16%). The high dose of CA increased C<sub>max</sub> (13%) with no impact on AUC<sub>0-72</sub> and decreased CL/F (23%). Furthermore, both doses of acidifying agents significantly increased liver enzyme levels and reduced body weight within two weeks. The results demonstrated that the PKs of both drugs were changed, and caution and close monitoring should be taken with ERL and GEF when co-administered with an acidifying agent.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 5","pages":"37"},"PeriodicalIF":3.4000,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Saudi Pharmaceutical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s44446-025-00032-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Erlotinib (ERL) and Gefitinib (GEF) are weakly basic drugs with pH-dependent solubility profiles mainly dependent on stomach pH. We proposed possible drug and/or food-drug interactions with acidifying agents. Citric acid (CA) and phosphoric acid (PPA) are the most common acidifying agents used in food and medication to treat certain conditions. This study evaluated the impact of concomitant consumption of CA and PA on ERL and GEF pharmacokinetic parameters (PKs). The PKs of ERL and GEF were investigated in rats after four weeks of CA and PPA consumption in low (175 mg/kg) and high (100 mg/kg) doses using UPLC-MS/MS. Data indicated that acidifying agents altered PKs of ERL and GEF dose-dependently. High doses of CA and PPA significantly increased the Cmax of ERL by 103% and 218%, the AUC0-72 by 35% and 78%, respectively, while reducing CL/F by 44% with CA and 74% with PPA. For GEF, Low and high doses of PPA increased Cmax and Tmax with a reduction of CL/F. A low dose of CA did not impact Cmax, significantly decreased AUC0-72 (28%), and increased CL/F (16%). The high dose of CA increased Cmax (13%) with no impact on AUC0-72 and decreased CL/F (23%). Furthermore, both doses of acidifying agents significantly increased liver enzyme levels and reduced body weight within two weeks. The results demonstrated that the PKs of both drugs were changed, and caution and close monitoring should be taken with ERL and GEF when co-administered with an acidifying agent.

酸化剂影响厄洛替尼和吉非替尼药代动力学参数并升高Wistar大鼠肝酶。
厄洛替尼(ERL)和吉非替尼(GEF)是弱碱性药物,其溶解度主要依赖于胃ph值。我们提出了可能与酸化剂的药物和/或食品药物相互作用。柠檬酸(CA)和磷酸(PPA)是食品和药物中最常用的酸化剂,用于治疗某些疾病。本研究评估了CA和PA同时摄入对ERL和GEF药代动力学参数(PKs)的影响。采用UPLC-MS/MS法研究大鼠低剂量(175 mg/kg)和高剂量(100 mg/kg)摄入CA和PPA 4周后ERL和GEF的PKs。数据显示酸化剂对ERL和GEF的PKs的改变呈剂量依赖性。高剂量CA和PPA使ERL的Cmax分别增加103%和218%,AUC0-72分别增加35%和78%,而CA和PPA分别使CL/F降低44%和74%。对于GEF,低剂量和高剂量PPA增加Cmax和Tmax,降低CL/F。低剂量CA不影响Cmax,显著降低AUC0-72(28%),增加CL/F(16%)。高剂量CA增加Cmax(13%),对AUC0-72无影响,降低CL/F(23%)。此外,两种剂量的酸化剂在两周内显著增加了肝酶水平并减轻了体重。结果表明,两种药物的PKs发生了变化,与酸化剂合用ERL和GEF时应谨慎密切监测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Saudi Pharmaceutical Journal
Saudi Pharmaceutical Journal PHARMACOLOGY & PHARMACY-
CiteScore
6.10
自引率
2.40%
发文量
194
审稿时长
67 days
期刊介绍: The Saudi Pharmaceutical Journal (SPJ) is the official journal of the Saudi Pharmaceutical Society (SPS) publishing high quality clinically oriented submissions which encompass the various disciplines of pharmaceutical sciences and related subjects. SPJ publishes 8 issues per year by the Saudi Pharmaceutical Society, with the cooperation of the College of Pharmacy, King Saud University.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信