{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:26:29Z","timestamp":1784042789551,"version":"3.55.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100007130","name":"University of Texas System","doi-asserted-by":"publisher","award":["250439\/39411"],"award-info":[{"award-number":["250439\/39411"]}],"id":[{"id":"10.13039\/100007130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007130","name":"University of Texas System","doi-asserted-by":"publisher","award":["1R21AI148096"],"award-info":[{"award-number":["1R21AI148096"]}],"id":[{"id":"10.13039\/100007130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01HD099756"],"award-info":[{"award-number":["1R01HD099756"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NTM Education and Research"},{"name":"Vice President of Research"},{"DOI":"10.13039\/100016048","name":"University of Texas at Tyler","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Poor sustained sputum culture conversion rates with the standard-of-care therapy highlight the need for better drugs to treat Mycobacterium avium complex pulmonary disease (MAC-PD).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine the pharmacokinetics\/pharmacodynamics (PK\/PD)-optimized exposure of sarecycline and its potential role in treating MAC-PD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed MIC studies with MAC ATCC 700898 and 19 clinical isolates and test-tube static concentration\u2013response studies. A dynamic hollow-fibre system model of intracellular MAC (HFS-MAC) study was performed mimicking six human-equivalent sarecycline dose concentration\u2013time profiles to identify the PK\/PD optimal exposure of sarecycline for MAC kill. The inhibitory sigmoid maximal effect (Emax) model was used for PK\/PD analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The sarecycline MIC of MAC ATCC 700898 was 1 mg\/L, while the MIC for the 19 clinical strains ranged between 32 and &amp;gt;256 mg\/L. The concentration mediating 50% of Emax (EC50) was similar between intracellular and extracellular MAC. In the HFS-MAC, all six sarecycline doses killed intracellular MAC, with an Emax of 1.0 log10 cfu\/mL below Day 0 burden (stasis). The sarecycline EC80 (optimal) exposure was identified as AUC0\u201324\/MIC = 139.46.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Sarecycline demonstrated anti-MAC Emax in the HFS-MAC model better than ethambutol but worse than omadacycline (&amp;gt;5 log10 cfu\/mL below stasis) in HFS-MAC. However, since currently approved highest oral sarecycline dose achieves an AUC0\u201324 of 48.2 mg\u00b7h\/L and MAC MICs are &amp;gt;32 mg\/L, the target AUC0\u201324\/MIC of 139.46 is unlikely to be achieved in patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad352","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T07:15:41Z","timestamp":1699600541000},"page":"96-99","source":"Crossref","is-referenced-by-count":9,"title":["Sarecycline pharmacokinetics\/pharmacodynamics in the hollow-fibre model of <i>Mycobacterium avium<\/i> complex: so near and yet so far"],"prefix":"10.1093","volume":"79","author":[{"given":"Sanjay","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Medicine, School of Medicine, University of Texas at Tyler , 11937 US Highway 271, Tyler, TX 75708 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunavanthi D","family":"Boorgula","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of Texas at Tyler , 11937 US Highway 271, Tyler, TX 75708 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Aryal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Health Outcomes, The Ben and Maytee Fisch College of Pharmacy, University of Texas at Tyler , Tyler, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie V","family":"Philley","sequence":"additional","affiliation":[{"name":"Section of Pulmonary and Critical Care, School of Medicine, University of Texas at Tyler , Tyler, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7592-8012","authenticated-orcid":false,"given":"Tawanda","family":"Gumbo","sequence":"additional","affiliation":[{"name":"Quantitative Preclinical & Clinical Sciences Department, Praedicare Inc. , Dallas, TX , USA"},{"name":"Hollow Fiber System & Experimental Therapeutics Laboratories, Praedicare Inc , Dallas, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashikant","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of Texas at Tyler , 11937 US Highway 271, Tyler, TX 75708 , USA"},{"name":"Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler , Tyler, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,8]]},"reference":[{"key":"2024042100595953400_dkad352-B1","doi-asserted-by":"crossref","first-page":"i3","DOI":"10.1093\/jac\/dkx311","article-title":"Meta-analyses and the evidence base for microbial outcomes in the treatment of pulmonary Mycobacterium avium-intracellulare complex 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