ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)最新文献

{"title":"The metabolism of the 8-aminoquinolines in relation to hemolytic toxicity: exploring current understanding for future antimalarial drug discovery","authors":"P. Fasinu","doi":"10.1124/jpet.122.140510","DOIUrl":"https://doi.org/10.1124/jpet.122.140510","url":null,"abstract":"","PeriodicalId":112046,"journal":{"name":"ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125820327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unusual Metabolism of Benzethonium by Cytochrome P450","authors":"Ryan P. Seguin, Libin Xu, Ryan Nguyen","doi":"10.1124/jpet.122.564180","DOIUrl":"https://doi.org/10.1124/jpet.122.564180","url":null,"abstract":"Abstract","PeriodicalId":112046,"journal":{"name":"ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128567576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of endogenous biomarkers of renal organic cation transporters in rats by global metabolomics analysis","authors":"Anoud Ailabouni, V. Mettu, D. K. Singh, Aarzoo Thakur, B. Prasad","doi":"10.1124/jpet.122.181830","DOIUrl":"https://doi.org/10.1124/jpet.122.181830","url":null,"abstract":"Abstract","PeriodicalId":112046,"journal":{"name":"ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)","volume":"74 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122542413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-nutritive Sweeteners Acesulfame Potassium and Sucralose Competitively Inhibit P-glycoprotein","authors":"L. Danner, S. O. Stichelen","doi":"10.1124/jpet.122.253080","DOIUrl":"https://doi.org/10.1124/jpet.122.253080","url":null,"abstract":"Non-nutritive sweeteners (NNS) are popular sugar replacements that are used in a wide range of foods, beverages, and medications. Although NNS are recognized as safe by the Food and Drug Administration, the effects of NNS on specific patient populations and human development are not completely understood. Previously, our lab showed that mouse pups exposed to NNS during early development present compromised liver detoxification. Thus, we questioned whether NNS might disrupt detoxification in the liver, including efflux transporters such as P-glycoprotein ( ABCB1/ PGP). We hypothesize that two common NNS, acesulfame potassium (AceK) and sucralose (Sucr), inhibit PGP ’ s efflux function and alter PGP expression, suggesting reduced detoxification capacity and altered distribution of certain drugs. To investigate the effects of NNS on PGP, we first exposed the HepG2 liver carcinoma cell line to AceK and Sucr and assessed ABCB1/ PGP transcript and protein levels. Combined NNS treatment significantly increased ABCB1 expression and PGP levels, an effect also commonly observed with some PGP inhibitor drugs. We, therefore, investigated NNS effects on PGP ’ s efflux action. An in vitro PGP substrate retention assay performed in HepG2 and HEK293 demonstrated that combined NNS significantly increased the intracellular retention of PGP substrate Calcein-AM, confirming PGP inhibition by NNS. Individual AceK or Sucr incubation on HepG2 cells also significantly inhibited PGP efflux, validating the PGP inhibition by both compounds. In a cell-free assay measuring PGP ’ s ATPase activity, AceK and Sucr also significantly increased PGP ATPase activity in a dose-dependent manner, revealing them as competitive inhibitors of PGP. Molecular docking experiments provided further insight into NNS interactions with PGP substrate binding pockets. Like Verapamil, Sucr was found to dock primarily in PGP ’ s main high-affinity binding pocket. AceK shows a lower affinity for this pocket and docks mainly in two other sites within PGP ’ s inward-facing transmembrane channel. To conclude, our results provide evidence that two common NNS, AceK and Sucr, are substrates and competitive inhibitors of PGP, impacting PGP both functionally and at the level of mRNA and protein. Most importantly, altered PGP function was observed after exposure to concentrations of NNS within expected levels from common foods and beverage consumption, suggesting risks for NNS consumers when taking medications that are PGP substrates or modulators.","PeriodicalId":112046,"journal":{"name":"ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127708051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Resolution Mass Spectrometry Coupled with XCMS Online for High-throughput Detection and Identification of Drug Metabolites","authors":"Dilip Singh, V. Mettu, Aarzoo Thakur, Anoud Ailabouni, B. Prasad","doi":"10.1124/jpet.122.251350","DOIUrl":"https://doi.org/10.1124/jpet.122.251350","url":null,"abstract":"","PeriodicalId":112046,"journal":{"name":"ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)","volume":"51 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128820976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Novel DIA Based Proteomics Tools for Quantification of Drug-protein Adducts","authors":"Ellen Riddle, A. Zelter, N. Isoherranen","doi":"10.1124/jpet.122.276810","DOIUrl":"https://doi.org/10.1124/jpet.122.276810","url":null,"abstract":"","PeriodicalId":112046,"journal":{"name":"ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)","volume":"83 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117270620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Cytochrome P450 Interactions with Redox Partner Cytochrome P450 Reductase","authors":"Sarah D. Burris-Hiday, M. Chai, M. Gross, E. Scott","doi":"10.1124/jpet.122.267650","DOIUrl":"https://doi.org/10.1124/jpet.122.267650","url":null,"abstract":"","PeriodicalId":112046,"journal":{"name":"ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127715341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Pazopanib as an OATP1B1 Substrate from a Competitive Counterflow Screen","authors":"Thomas Drabison, Mike Boeckman, Eric D. Eisenmann, S. Baker, Shuiying Hu, A. Sparreboom, Z. Talebi","doi":"10.1124/jpet.122.555040","DOIUrl":"https://doi.org/10.1124/jpet.122.555040","url":null,"abstract":"","PeriodicalId":112046,"journal":{"name":"ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127041849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of CNT1 and CNT3 to the intestinal transport and pharmacokinetics of decitabine","authors":"N. Anabtawi, Thomas Drabison, Mike Boeckman, Yan Jin, M. Halpin, A. Gibson, A. Sparreboom, Raj Govindarajan, S. Baker","doi":"10.1124/jpet.122.212000","DOIUrl":"https://doi.org/10.1124/jpet.122.212000","url":null,"abstract":"","PeriodicalId":112046,"journal":{"name":"ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125512443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A NovelIn VitroHepatocyte Culture System (icHep) for Biliary Drug Excretion Analysis Using Permeation Assay","authors":"Y. Nakazono, H. Arakawa, Natsumi Matsuoka, Y. Shirasaka, I. Tamai","doi":"10.1124/jpet.122.156040","DOIUrl":"https://doi.org/10.1124/jpet.122.156040","url":null,"abstract":"","PeriodicalId":112046,"journal":{"name":"ASPET 2023 Annual Meeting Abstract - Drug Metabolism and Disposition (DMD)","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116497436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}