{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T08:48:54Z","timestamp":1769762934993,"version":"3.49.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Rifapentine (RPT) is a rifamycin antimycobacterial and, as part of a combination therapy, is indicated for the treatment of pulmonary tuberculosis (TB) caused by\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>\n            . Although the results from a number of studies indicate that rifapentine has the potential to shorten treatment duration and enhance completion rates compared to other rifamycin agents utilized in antituberculosis drug regimens (i.e., regimens 1 to 4), its optimal dose and exposure in humans are unknown. To help inform such an optimization, a physiologically based pharmacokinetic (PBPK) model was developed to predict time course, tissue-specific concentrations of RPT and its active metabolite, 25-desacetyl rifapentine (dRPT), in humans after specified administration schedules for RPT. Starting with the development and verification of a PBPK model for rats, the model was extrapolated and then tested using human pharmacokinetic data. Testing and verification of the models included comparisons of predictions to experimental data in several rat tissues and time course RPT and dRPT plasma concentrations in humans from several single- and repeated-dosing studies. Finally, the model was used to predict RPT concentrations in the lung during the intensive and continuation phases of a current recommended TB treatment regimen. Based on these results, it is anticipated that the PBPK model developed in this study will be useful in evaluating dosing regimens for RPT and for characterizing tissue-level doses that could be predictors of problems related to efficacy or safety.\n          <\/jats:p>","DOI":"10.1128\/aac.00031-16","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T03:23:45Z","timestamp":1465269825000},"page":"4860-4868","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Physiologically Based Pharmacokinetic Model of Rifapentine and 25-Desacetyl Rifapentine Disposition in Humans"],"prefix":"10.1128","volume":"60","author":[{"given":"Todd J.","family":"Zurlinden","sequence":"first","affiliation":[{"name":"Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garrett J.","family":"Eppers","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brad","family":"Reisfeld","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado, USA"},{"name":"School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140050-00002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200905-0795OC"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/508278"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/46.4.565"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05128-14"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.323"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023276808298"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011960428896"},{"key":"e_1_3_2_10_2","first-page":"437","article-title":"Single and multiple dose pharmacokinetics of rifapentine in man: part II","volume":"3","author":"Keung AC","year":"1999","unstructured":"Keung AC, Eller MG, McKenzie KA, Weir SJ. 1999. 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