{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:21:29Z","timestamp":1791321689250,"version":"4.3.1"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Paratek Pharmaceuticals, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We assessed the plasma and soft-tissue pharmacokinetic exposure of omadacycline in infected patients with diabetic foot infection (DFI) and healthy volunteers using in vivo microdialysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Eight patients and six healthy volunteers were enrolled and received an omadacycline IV loading dose (200\u2005mg) followed by two oral doses (300\u2005mg) every 24\u2005h. Microdialysis catheters were placed in the soft tissue near the infected diabetic foot wound (patients) or thigh (healthy volunteers). Plasma and dialysate fluid samples were collected, starting immediately prior to the third dose and continued for 24\u2005h post-dose. Protein binding was determined by ultracentrifugation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The mean \u00b1 SD omadacycline pharmacokinetic parameters in plasma for infected patients and healthy volunteers were: Cmax, 0.57 \u00b1 0.15 and 1.14 \u00b1 0.26\u2005mg\/L; t\u00bd, 16.19 \u00b1 5.06 and 25.34 \u00b1 12.92\u2005h; and total omadacycline AUC0\u201324, 6.27 \u00b1 1.38 and 14.06 \u00b1 3.40\u2005mg\u00b7h\/L, respectively. The omadacycline mean plasma free fraction was 0.21 and 0.20 for patients and healthy volunteers, corresponding to free plasma AUC0\u201324 of 1.13 \u00b1 0.37 and 2.78 \u00b1 0.55\u2005mg\u00b7h\/L, respectively. Omadacycline tissue AUC0\u201324 was 0.82 \u00b1 0.38 and 1.37 \u00b1 0.48\u2005mg\u00b7h\/L for patients and volunteers, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The present study describes the plasma and soft-tissue exposure of omadacycline in patients with DFI and healthy volunteers. Integrating these data with the microbiological, pharmacokinetic\/pharmacodynamic and clinical efficacy data is foundational to support clinical assessments of omadacycline efficacy specifically for DFI. This, coupled with the once-daily oral administration, suggests omadacycline could be an advantageous translational therapy for the hospital and outpatient setting.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac055","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T04:18:46Z","timestamp":1644898726000},"page":"1372-1378","source":"Crossref","is-referenced-by-count":14,"title":["Omadacycline pharmacokinetics and soft-tissue penetration in diabetic patients with wound infections and healthy volunteers using <i>in vivo<\/i> microdialysis"],"prefix":"10.1093","volume":"77","author":[{"given":"Christian M","family":"Gill","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Fratoni","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley K","family":"Shepard","sequence":"additional","affiliation":[{"name":"Hartford Healthcare Medical Group, Podiatric Surgery, Hartford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L","family":"Kuti","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA"},{"name":"Division of Infectious Diseases, Hartford Hospital, Hartford, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"2022042812410172200_dkac055-B1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.idc.2020.10.007","article-title":"Skin and soft tissue infections in patients with diabetes mellitus","volume":"35","author":"Polk","year":"2021","journal-title":"Infect Dis Clin North Am"},{"key":"2022042812410172200_dkac055-B2","doi-asserted-by":"crossref","first-page":"e60057","DOI":"10.1371\/journal.pone.0060057","article-title":"Skin and soft tissue infections and associated complications among commercially insured patients aged 0-64 years with and without diabetes in the U.S","volume":"8","author":"Suaya","year":"2013","journal-title":"PLoS One"},{"key":"2022042812410172200_dkac055-B3","doi-asserted-by":"crossref","first-page":"936","DOI":"10.2337\/dc16-2189","article-title":"Health care service and outcomes among an estimated 6.7 million 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penetration between diabetic patients with wound infections and healthy volunteers via in vivo microdialysis","volume":"62","author":"Stainton","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2022042812410172200_dkac055-B10","doi-asserted-by":"crossref","first-page":"e02263-19","DOI":"10.1128\/AAC.02263-19","article-title":"Population pharmacokinetic analyses for omadacycline using Phase 1 and 3 data","volume":"64","author":"Lakota","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"2022042812410172200_dkac055-B11","doi-asserted-by":"crossref","first-page":"e01135-17","DOI":"10.1128\/AAC.01135-17","article-title":"Comparison of omadacycline and tigecycline pharmacokinetics in the plasma, epithelial lining fluid, and alveolar cells of healthy adult subjects","volume":"61","author":"Gotfried","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2022042812410172200_dkac055-B12","article-title":"In vitro protein binding with 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