{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:48:56Z","timestamp":1761101336512,"version":"3.41.2"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Theravance Biopharma R&D, Inc.","award":["TLV-2015-011"],"award-info":[{"award-number":["TLV-2015-011"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            A recommended total-body-weight (TBW) dosing strategy for telavancin may not be optimal in obese patients. The primary objective of this study was to characterize and compare the pharmacokinetics (PK) of telavancin across four body size groups: normal to overweight and obese classes I, II, and III. Healthy adult subjects (\n            <jats:italic>n<\/jats:italic>\n            = 32) received a single, weight-stratified, fixed dose of 500 mg (\n            <jats:italic>n<\/jats:italic>\n            = 4), 750 mg (\n            <jats:italic>n<\/jats:italic>\n            = 8), or 1,000 mg (\n            <jats:italic>n<\/jats:italic>\n            = 20) of telavancin. Noncompartmental PK analyses revealed that subjects with a body mass index (BMI) of \u226540 kg\/m\n            <jats:sup>2<\/jats:sup>\n            had a higher volume of distribution (16.24 \u00b1 2.7 liters) than subjects with a BMI of &lt;30 kg\/m\n            <jats:sup>2<\/jats:sup>\n            (11.71 \u00b1 2.6 liters). The observed area under the concentration-time curve from time zero to infinity (AUC\n            <jats:sub>0\u2013\u221e<\/jats:sub>\n            ) ranged from 338.1 to 867.3 mg \u00b7 h\/liter, with the lowest exposures being in subjects who received 500 mg. AUC\n            <jats:sub>0\u2013\u221e<\/jats:sub>\n            values were similar among obese subjects who received 1,000 mg. A two-compartment population PK model best described the plasma concentration-time profile of telavancin when adjusted body weight (ABW) was included as a predictive covariate. Fixed doses of 750 mg and 1,000 mg had similar target attainment probabilities for efficacy as doses of 10 mg\/kg of body weight based on ABW and TBW, respectively. However, the probability of achieving a target area under the concentration-time curve from time zero to 24 h of \u2265763 mg \u00b7 h\/liter in association with acute kidney injury was highest (19.7%) with TBW-simulated dosing and lowest (0.4%) at the 750-mg dose. These results suggest that a fixed dose of 750 mg is a safe and effective alternative to telavancin doses based on TBW or ABW for the treatment of obese patients with normal renal function and Staphylococcus\n            <jats:named-content content-type=\"genus-species\">aureus<\/jats:named-content>\n            infections. (This study has been registered at ClinicalTrials.gov under identifier NCT02753855.)\n          <\/jats:p>","DOI":"10.1128\/aac.02475-17","type":"journal-article","created":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T11:57:37Z","timestamp":1515499057000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Pharmacokinetics of Telavancin at Fixed Doses in Normal-Body-Weight and Obese (Classes I, II, and III) Adult Subjects"],"prefix":"10.1128","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7646-0594","authenticated-orcid":false,"given":"Kristen L.","family":"Bunnell","sequence":"first","affiliation":[{"name":"University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manjunath P.","family":"Pai","sequence":"additional","affiliation":[{"name":"University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Sikka","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan C.","family":"Bleasdale","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3914-8400","authenticated-orcid":false,"given":"Eric","family":"Wenzler","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry H.","family":"Danziger","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois, USA"},{"name":"University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A.","family":"Rodvold","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago, College of Pharmacy, Chicago, Illinois, USA"},{"name":"University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ534"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-016-2865-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2016.12.009"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01210-14"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03172-14"},{"key":"e_1_3_2_7_2","volume-title":"Telavancin for injection (Vibativ) prescribing information","author":"Theravance Biopharma Antibiotics, Inc","year":"2016","unstructured":"Theravance Biopharma Antibiotics, Inc. 2016. 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