دورية أكاديمية
Physiologically Based Pharmacokinetic Models of Probenecid and Furosemide to Predict Transporter Mediated Drug-Drug Interactions
| العنوان: | Physiologically Based Pharmacokinetic Models of Probenecid and Furosemide to Predict Transporter Mediated Drug-Drug Interactions |
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| المؤلفون: | Britz, Hannah, Hanke, Nina, Taub, Mitchell E., Wang, Ting, Prasad, Bhagwat, Fernandez, Éric, Stopfer, Peter, Nock, Valerie, Lehr, Thorsten |
| المصدر: | http://lobid.org/resources/99370672103606441Test#!, 37(12):250. |
| سنة النشر: | 2020 |
| المجموعة: | Publisso (ZB MED-Publikationsportal Lebenswissenschaften) |
| مصطلحات موضوعية: | probenecid, Biotransformation [MeSH], drug-drug interaction (DDI), Organic Anion Transporters/antagonists, Computer Simulation [MeSH], Models, Biological [MeSH], Furosemide/administration, Administration, Oral [MeSH], Male [MeSH], Probenecid/blood [MeSH], Probenecid/pharmacokinetics [MeSH], Drug Interactions [MeSH], physiologically based pharmacokinetic modeling (PBPK), Rifampin/pharmacokinetics [MeSH], Probenecid/administration, Female [MeSH], organic anion transporter (OAT), Adult [MeSH], Humans [MeSH], furosemide, Furosemide/pharmacokinetics [MeSH], Intravenous [MeSH], Research Paper, Furosemide/blood [MeSH], Drug Elimination Routes [MeSH], Organic Anion Transporters/metabolism [MeSH] |
| الوصف: | Purpose!#!To provide whole-body physiologically based pharmacokinetic (PBPK) models of the potent clinical organic anion transporter (OAT) inhibitor probenecid and the clinical OAT victim drug furosemide for their application in transporter-based drug-drug interaction (DDI) modeling.!##!Methods!#!PBPK models of probenecid and furosemide were developed in PK-Sim®. Drug-dependent parameters and plasma concentration-time profiles following intravenous and oral probenecid and furosemide administration were gathered from literature and used for model development. For model evaluation, plasma concentration-time profiles, areas under the plasma concentration-time curve (AUC) and peak plasma concentrations (C!##!Results!#!The developed models accurately describe the reported plasma concentrations of 27 clinical probenecid studies and of 42 studies using furosemide. Furthermore, application of these models to predict the probenecid-furosemide and probenecid-rifampicin DDIs demonstrates their good performance, with 6/7 of the predicted DDI AUC ratios and 4/5 of the predicted DDI C!##!Conclusions!#!Whole-body PBPK models of probenecid and furosemide were built and evaluated, providing useful tools to support the investigation of transporter mediated DDIs. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://repository.publisso.de/resource/frl:6466472Test; https://doi.org/10.1007/s11095-020-02964-zTest; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688195Test/ |
| DOI: | 10.1007/s11095-020-02964-z |
| الإتاحة: | https://doi.org/10.1007/s11095-020-02964-zTest https://repository.publisso.de/resource/frl:6466472Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688195Test/ |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.B7AC10AA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s11095-020-02964-z |
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