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For rifabutin, differing intragastric concentrations based on dosing regimen may account for differences in reported eradication rates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To compare intragastric rifabutin concentrations between low\u2010dose rifabutin (50\u2009mg three time daily; as in RHB\u2010105) and generically dosed rifabutin 150\u2009mg once daily, 150\u2009mg twice daily, and 300\u2009mg once daily using a validated Physiologically\u2010based pharmacokinetic (PBPK) model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We obtained plasma pharmacokinetic data from the RHB\u2010105 clinical development programs and used it to develop and validate a whole\u2010body PBPK model using PK\u2010SIM software. We modified the existing rifabutin model to include the impact of omeprazole on gastric pH and emptying time. Modelled intragastric rifabutin exposure was expressed as the time that each regimen maintained its concentration \u2265MIC<jats:sub>90<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rifabutin 50\u2009mg three times daily achieved significantly longer times with intragastric concentration above MIC<jats:sub>90<\/jats:sub> (22.3\u2009\u00b1\u20091.1\u2009h) than 150\u2009mg once daily (8.3\u2009\u00b1\u20091.7\u2009h), 150\u2009mg twice daily (16.3\u2009\u00b1\u20092.3\u2009h), or 300\u2009mg once daily (8.5\u2009\u00b1\u20091.9\u2009h) while providing the lowest mean maximal plasma concentration and mean area under the plasma concentration\u2013time curve of all regimens studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PBPK modelling showed rifabutin 50\u2009mg three times daily had higher intragastric exposure times than 150\u2009mg once daily or twice daily, or 300\u2009mg once daily. This low\u2010dose rifabutin regimen provides the highest potential for <jats:italic>H. pylori<\/jats:italic> eradication while minimising systemic rifabutin exposure.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17526","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T06:07:06Z","timestamp":1682057226000},"page":"159-167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Physiologically\u2010based pharmacokinetic modelling to predict intragastric rifabutin concentrations in the treatment of <i>Helicobacter pylori<\/i> infection"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0987-0662","authenticated-orcid":false,"given":"Colin W.","family":"Howden","sequence":"first","affiliation":[{"name":"University of Tennessee College of Medicine  Memphis Tennessee 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