{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T13:32:37Z","timestamp":1782135157071,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T00:00:00Z","timestamp":1444089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Merial"},{"name":"Duluth"},{"name":"Georgia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>The objectives of this study were to determine (i) whether an association exists between individual pharmacokinetic parameters and treatment outcome when feeder cattle were diagnosed with bovine respiratory disease (<jats:styled-content style=\"fixed-case\">BRD<\/jats:styled-content>) and treated with gamithromycin (Zactran<jats:sup>\u00ae<\/jats:sup>) at the label dose and (ii) whether there was a stronger association between treatment outcome and gamithromycin concentration in plasma or in the pulmonary epithelial lining fluid (<jats:styled-content style=\"fixed-case\">PELF<\/jats:styled-content>) effect compartment. The study design was a prospective, blinded, randomized clinical trial utilizing three groups of 60 (362\u2013592\u00a0lb) steers\/bulls randomly allocated within origin to sham injection or gamithromycin mass medication. Cattle were evaluated daily for signs of <jats:styled-content style=\"fixed-case\">BRD<\/jats:styled-content> by a veterinarian blinded to treatment. Animals meeting the <jats:styled-content style=\"fixed-case\">BRD<\/jats:styled-content> case definition were enrolled and allocated to a sample collection scheme consisting of samples for bacterial isolation (bronchoalveolar lavage fluid and nasopharyngeal swabs) and gamithromycin concentration determination (<jats:styled-content style=\"fixed-case\">PELF<\/jats:styled-content> and plasma). Gamithromycin susceptibility of <jats:italic>M.\u00a0haemolytica<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a0287) and <jats:italic>P.\u00a0multocida<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a0257) were determined using broth microdilution with frozen panels containing gamithromycin at concentrations from 0.03 to 16\u00a0\u03bcg\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>. A two\u2010compartment plasma pharmacokinetic model with an additional compartment for gamithromycin in <jats:styled-content style=\"fixed-case\">PELF<\/jats:styled-content> was developed using rich data sets from published and unpublished studies. The sparse data from our study were then fit to this model using nonlinear mixed effects modeling to estimate individual parameter values. The resulting parameter estimates were used to simulate full time\u2013concentration profiles for each animal in this study. These profiles were analyzed using noncompartmental methods so that <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> indices (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>24<\/jats:sub>\/<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> AUC<\/jats:styled-content><jats:sub>\u221e<\/jats:sub>\/<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> C<jats:sub>MAX<\/jats:sub><\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content>) could be calculated for plasma and <jats:styled-content style=\"fixed-case\">PELF<\/jats:styled-content> (also T&gt;<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content>) for each individual. The calculated <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> indices were indicative that for both <jats:italic>M.\u00a0haemolytica<\/jats:italic> and <jats:italic>P.\u00a0multocida<\/jats:italic> a higher drug exposure in terms of concentration, and duration of exposure relative to the <jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content> of the target pathogen, was favorable to a successful case outcome. A\u00a0significant association was found between treatment success and <jats:styled-content style=\"fixed-case\">PELF AUC<\/jats:styled-content><jats:sub>0\u201324<\/jats:sub>\/<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content> for <jats:italic>P.\u00a0multocida<\/jats:italic>. The calves in this study demonstrated an increased clearance and volume of distribution in plasma as compared to the healthy calves in two previously published reports. Ultimately, the findings from this study indicate that higher <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> indices were predictive of positive treatment outcomes.<\/jats:p>","DOI":"10.1111\/jvp.12267","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T06:02:46Z","timestamp":1444111366000},"page":"157-166","source":"Crossref","is-referenced-by-count":34,"title":["Pharmacokinetics and pharmacodynamics of gamithromycin in pulmonary epithelial lining fluid in naturally occurring bovine respiratory disease in multisource commingled feedlot cattle"],"prefix":"10.1111","volume":"39","author":[{"given":"K. D.","family":"DeDonder","sequence":"first","affiliation":[{"name":"Diagnostic Medicine\/Pathobiology Kansas State University College of Veterinary Medicine Manhattan KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. D.","family":"Apley","sequence":"additional","affiliation":[{"name":"Clinical Sciences Kansas State University College of Veterinary Medicine Manhattan KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Computational Comparative Medicine Kansas State University College of Veterinary Medicine Manhattan KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Gehring","sequence":"additional","affiliation":[{"name":"Institute of Computational Comparative Medicine Kansas State University College of Veterinary Medicine Manhattan KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. M.","family":"Harhay","sequence":"additional","affiliation":[{"name":"USDA ARS US Meat Animal Research Center Clay Center NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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