{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:52:15Z","timestamp":1785437535913,"version":"3.56.0"},"reference-count":28,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Telavancin is an intravenously administered lipoglycopeptide antibiotic active against clinically relevant gram-positive pathogens. In these analyses, a population pharmacokinetic (PK) model was constructed to describe the time course of telavancin in plasma and epithelial lining fluid (ELF) using data from healthy subjects and patients with complicated skin and skin-structure infections, hospital-acquired and ventilator-associated bacterial pneumonia, or uncomplicated bacteremia across Phases 1\u20134 of clinical development. Data from 1,205 individuals pooled from 21 studies contributed a total of 9,088 telavancin plasma concentrations. The final model for telavancin was a two-compartment model with zero-order intravenous input and linear elimination. Dialysis clearance was included as part of the base structural PK model; the relationship between telavancin clearance and creatinine clearance was included\n                      <jats:italic toggle=\"yes\">a priori<\/jats:italic>\n                      . Body weight, age, and infection type were identified as statistically significant predictors of the interindividual variability (IIV) in total clearance. Body weight, age, and infection type were also identified as statistically significant predictors of IIV for the central and peripheral volumes of distribution. Only body weight was found to be a significant predictor of the IIV in distributional clearance. The model for ELF did not reveal any appreciable biases and determined the average free-drug ELF penetration ratio to be 73.0%. In summary, the population PK model characterized the time course of telavancin in both plasma and ELF robustly, captured the impact of clinically meaningful patient covariate effects, including removal of drug due to hemodialysis, and provided reliable individual\n                      <jats:italic toggle=\"yes\">post hoc<\/jats:italic>\n                      estimates of exposure in subjects enrolled in the clinical studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01382-24","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T09:35:11Z","timestamp":1749720911000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetic analyses for telavancin using data from healthy subjects and patients with infections"],"prefix":"10.1128","author":[{"given":"Scott A.","family":"Van Wart","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02gck7e73","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Clinical Pharmacodynamics","place":["Schenectady, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0452-682X","authenticated-orcid":true,"given":"M. Courtney","family":"Safir","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02gck7e73","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Clinical Pharmacodynamics","place":["Schenectady, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4891-6467","authenticated-orcid":true,"given":"Sujata M.","family":"Bhavnani","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02gck7e73","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Clinical Pharmacodynamics","place":["Schenectady, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4730-0655","authenticated-orcid":true,"given":"Thomas P.","family":"Lodise","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/014hfaw95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences","place":["Albany, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3172-0847","authenticated-orcid":true,"given":"Christopher M.","family":"Rubino","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02gck7e73","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Clinical Pharmacodynamics","place":["Schenectady, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"e_1_3_4_2_2","unstructured":"Vibativ (telavancin) [package insert]. 2023. Cumberland Pharmaceuticals Inc Nashville TN."},{"key":"e_1_3_4_3_2","unstructured":"Tabuk and Cumberland partner to bring innovative antibiotic with life-saving potential to Middle East [press release]. 2022. Cumberland Pharmaceuticals Nashville TN. Available from: https:\/\/investor.cumberlandpharma.com\/news-releases\/news-release-details\/tabuk-and-cumberland-partner-bring-innovative-antibiotic-life. Retrieved 14 Mar 2025."},{"key":"e_1_3_4_4_2","unstructured":"Theravance biopharma announces marketing authorization for VIBATIV (Telavancin) in Russia for treatment of multiple infections caused by Gram-positive bacteria including MRSA [press release]. 2015. Theravance Biopharma Dublin."},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01110-07"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05915-11"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00383-11"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.30.2.136"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009337133"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02475-17"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-14-289"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab370"},{"key":"e_1_3_4_13_2","volume-title":"Clin Microbiol Infect","volume":"10","author":"Rodvold KA","year":"2004","unstructured":"Rodvold KA, Gotfried MH, Loutit JS, Porter SB. 2004. Plasma and intrapulmonary concentrations of oritavancin and vancomycin in normal healthy adults. Abstract NO. O-254. 14th European Congress of Clinical Microbiology and Infectious Diseases; May 1 to 4, 2004. Prague, Czech Republic. Clin Microbiol Infect. Vol. 10 Supplement 3:44."},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01024-19"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00712-11"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.1.195-201.2005"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn273"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.30.8.806"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.2.788-790.2006"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00875-07"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.30.1.35"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/429914"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.3.862-867.2006"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1086\/587896"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq031"},{"key":"e_1_3_4_26_2","unstructured":"SAS 9.4 for Windows [computer program]. 2013. SAS Institute Inc Cary NC."},{"key":"e_1_3_4_27_2","unstructured":"Bauer RJ. 2010. NONMEM users guides. NONMEM. Version 7.2. ICON Development Solutions Ellicott City MD."},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9255-z"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1986.60.2.532"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01382-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01382-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T09:35:12Z","timestamp":1749720912000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01382-24"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,6,12]]},"references-count":28,"alternative-id":["10.1128\/aac.01382-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01382-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,12]]},"assertion":[{"value":"2024-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01382-24"}}