{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:34:03Z","timestamp":1789652043746,"version":"4.0.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    Effectively treating multidrug\u2010resistant bacterial infections remains challenging due to the limited drug development pipeline and a scarcity of novel agents effective against these highly resistant pathogens. Bacteriophages (phages) are a potential addition to the antimicrobial treatment arsenal. Though, phages are currently being tested in clinical trials for antibiotic\u2010resistant infections, phages lack a fundamental understanding of optimal dosing in humans. Rationally designed preclinical studies using\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    infection models, allow us to assess clinically relevant phage +\/\u2212 antibiotic exposure (pharmacokinetics), the resulting treatment impact on the infecting pathogen (pharmacodynamics) and host immune response (immunodynamics). A mechanistic modeling framework allows us to integrate this knowledge gained from preclinical studies to develop predictive models. We reviewed recently published mathematical models based on\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\/or\n                    <jats:italic>in vivo<\/jats:italic>\n                    data that evaluate the effects of varying bacterial or phage densities, phage characteristics (burst size, adsorption rate), phage pharmacokinetics, phage\u2013antibiotic combinations and host immune responses. In our review, we analyzed study designs and the data used to inform the development of these mechanistic models. Insights gained from model\u2010based simulations were reviewed as they help identify crucial phage parameters for determining effective phage dosing. These efforts contribute to bridging the gap between phage therapy research and its clinical translation.\n                  <\/jats:p>","DOI":"10.1002\/cpt.3426","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T23:44:25Z","timestamp":1727135065000},"page":"94-105","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Crossing the Chasm: How to Approach Translational Pharmacokinetic\u2013Pharmacodynamic Modeling of Phage Dosing"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8704-7770","authenticated-orcid":false,"given":"Gauri G.","family":"Rao","sequence":"first","affiliation":[{"name":"USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1525-9993","authenticated-orcid":false,"given":"Quentin","family":"Vall\u00e9","sequence":"additional","affiliation":[{"name":"USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramya","family":"Mahadevan","sequence":"additional","affiliation":[{"name":"USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajnikant","family":"Sharma","sequence":"additional","affiliation":[{"name":"USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy J.","family":"Barr","sequence":"additional","affiliation":[{"name":"School of Biological Sciences Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Van Tyne","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"key":"e_1_2_17_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2214"},{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(00)01705-4"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.04.039"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2020.10.002"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02071-21"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00612-5"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac453"},{"key":"e_1_2_17_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30464-3"},{"key":"e_1_2_17_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01705-x"},{"key":"e_1_2_17_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0634-z"},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110825"},{"key":"e_1_2_17_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.631585"},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01470-20"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofad500.2474"},{"key":"e_1_2_17_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad480"},{"key":"e_1_2_17_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-164-6_18"},{"key":"e_1_2_17_17_1","first-page":"1","article-title":"Isolation and characterization of a novel virulent phage of Lactobacillus casei, ATCC 393","volume":"7","author":"Xi Z.","year":"2015","journal-title":"Food Environ. 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