{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:31:32Z","timestamp":1781613092596,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,8,8]],"date-time":"2016-08-08T00:00:00Z","timestamp":1470614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Zoetis Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>The pharmacokinetic (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) profile of tulathromycin, administered to calves subcutaneously at the dosage of 2.5\u00a0mg\/kg, was established in serum, inflamed (exudate), and noninflamed (transudate) fluids in a tissue cage model. The <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> profile of tulathromycin was also established in pneumonic calves. For <jats:italic>Mannheimia haemolytica<\/jats:italic> and <jats:italic>Pasteurella multocida<\/jats:italic>, tulathromycin minimum inhibitory concentrations (<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content>) were approximately 50 times lower in calf serum than in Mueller\u2013Hinton broth. The breakpoint value of the <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\/pharmacodynamic (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>) index (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>(0\u201324\u00a0h)<\/jats:sub>\/<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content>) to achieve a bactericidal effect was estimated from <jats:italic>in\u00a0vitro<\/jats:italic> time\u2010kill studies to be approximately 24\u00a0h for <jats:italic>M.\u00a0haemolytica<\/jats:italic> and <jats:italic>P.\u00a0multocida<\/jats:italic>. A population model was developed from healthy and pneumonic calves and, using Monte Carlo simulations, <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> cutoffs required for the development of antimicrobial susceptibility testing (<jats:styled-content style=\"fixed-case\">AST<\/jats:styled-content>) were determined. The population distributions of tulathromycin doses were established by Monte Carlo computation (<jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content>). The computation predicted a target attainment rate (<jats:styled-content style=\"fixed-case\">TAR<\/jats:styled-content>) for a tulathromycin dosage of 2.5\u00a0mg\/kg of 66% for <jats:italic>M.\u00a0haemolytica<\/jats:italic> and 87% for <jats:italic>P.\u00a0multocida<\/jats:italic>. The findings indicate that free tulathromycin concentrations in serum suffice to explain the efficacy of single\u2010dose tulathromycin in clinical use, and that a dosage regimen can be computed for tulathromycin using classical <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> concepts.<\/jats:p>","DOI":"10.1111\/jvp.12333","type":"journal-article","created":{"date-parts":[[2016,8,8]],"date-time":"2016-08-08T18:50:39Z","timestamp":1470682239000},"page":"16-27","source":"Crossref","is-referenced-by-count":49,"title":["Standard <scp>PK<\/scp>\/<scp>PD<\/scp> concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf"],"prefix":"10.1111","volume":"40","author":[{"given":"P.\u2010L.","family":"Toutain","sequence":"first","affiliation":[{"name":"UMR 1331 Toxalim INRA \u00c9cole Nationale V\u00e9t\u00e9rinaire de Toulouse Toulouse Cedex 03 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Potter","sequence":"additional","affiliation":[{"name":"The Royal Veterinary College Hatfield Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Pelligand","sequence":"additional","affiliation":[{"name":"The Royal Veterinary College Hatfield Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Lacroix","sequence":"additional","affiliation":[{"name":"UMR 1331 Toxalim INRA \u00c9cole Nationale V\u00e9t\u00e9rinaire de Toulouse Toulouse Cedex 03 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Illambas","sequence":"additional","affiliation":[{"name":"The Royal Veterinary College Hatfield Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Lees","sequence":"additional","affiliation":[{"name":"The Royal Veterinary College Hatfield Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.2001.62.1979"},{"key":"e_1_2_8_3_1","first-page":"1","volume-title":"Freedom Information Summary. 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