{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:28:04Z","timestamp":1789003684161,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T00:00:00Z","timestamp":1644710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004360","name":"Sveriges Lantbruksuniversitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004360","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Medicine &amp; Sci"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Septicaemia in the neonatal foal is caused by both Gram positive and Gram negative bacteria. The life\u2010threatening nature of this condition requires treatment to be initiated with broad spectrum antimicrobial drugs pending antimicrobial susceptibility testing. Potentiated sulphonamides, for example, trimethoprim combined with sulfadiazine, could be clinically relevant options but their pharmacokinetics in the neonatal foal are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To describe the plasma disposition of trimethoprim and sulfadiazine in neonatal foals and to relate the results to patterns in the minimum inhibitory concentration (MIC) for\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      , a recognized pathogen in neonatal foal sepsis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      A total of five doses of trimethoprim (2.5\u00a0mg\/kg) and sulfadiazine (12.5\u00a0mg\/kg) were administered intravenously every 12\u00a0h to eight neonatal foals that were 3 days old at inclusion. A non\u2010linear mixed effects model was fitted to the trimethoprim and sulfadiazine experimental data. The 24 h area under the free plasma trimethoprim and sulfadiazine concentration\u2010time curves (\n                      <jats:italic>f<\/jats:italic>\n                      AUC) and the pharmacokinetic\/pharmacodynamik (PK\/PD)\u2010index\n                      <jats:italic>f<\/jats:italic>\n                      AUC\/MIC was calculated to evaluate the potential clinical benefits of the administered dose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      For trimethoprim, the typical values were 1.99 L\/kg, 0.33 L\/h\u00b7kg and 4.2 h for the apparent volume of distribution, clearance and terminal half\u2010life, respectively. The 24 h\n                      <jats:italic>f<\/jats:italic>\n                      AUC for trimethoprim was 11.3\u00a0\u03bcg\u00b7h\/ml (7.2\u201315.2) and the\n                      <jats:italic>f<\/jats:italic>\n                      AUC\/MIC ratio for\n                      <jats:italic>E. coli<\/jats:italic>\n                      was 23 (16.4\u201329.2) (population mean (range)). For sulfadiazine, the typical values were 0.61 L\/kg, 0.09 L\/h\u00b7kg and 5.3 h for the apparent volume of distribution, clearance and terminal half\u2010life, respectively. The 24 h\n                      <jats:italic>f<\/jats:italic>\n                      AUC for sulfadiazine was 246.8\u00a0\u03bcg\u00b7h\/ml (175.6\u2013335.4).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>For trimethoprim, the plasma exposure is insufficient in some foals to successfully treat bacterial infections with an MIC\u2010value of 0.5\u00a0\u03bcg\/ml using the studied dosing regimen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/vms3.763","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T07:38:16Z","timestamp":1644737896000},"page":"1065-1071","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The disposition of trimethoprim and sulfadiazine in neonatal foals after intravenous administration"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7480-9935","authenticated-orcid":false,"given":"Carl","family":"Ekstrand","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Veterinary Public Health Division of Pharmacology and Toxicology Swedish University of Agricultural Sciences  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Nostell","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Swedish University of Agricultural Sciences  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronette","family":"Gehring","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Veterinary Public Health Division of Pharmacology and Toxicology Swedish University of Agricultural Sciences  Uppsala Sweden"},{"name":"Department of Population Health Sciences Division of Veterinary and Comparative Pharmacology Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Bondesson","sequence":"additional","affiliation":[{"name":"Department of Chemistry Environment and Feed Hygiene National Veterinary Institute (SVA)  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Br\u00f6jer","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Swedish University of Agricultural Sciences  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2015.02.001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0442.1979.tb00645.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0749-0739(17)30370-X"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-3306.1984.tb01945.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-9485-1_7"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-3306.1990.tb04207.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0749-0739(17)30694-6"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01301-08"},{"key":"e_1_2_11_10_1","first-page":"45","volume-title":"Pharmacokinetic and pharmacodynamic data analyses: Concepts and applications","author":"Gabrielsson J.","year":"2006"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.1998.tb02109.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2885.1999.00183.x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000507540"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-3306.1984.tb01942.x"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-3306.1984.tb01950.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2009.06.008"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cveq.2016.12.004"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1976.tb03104.x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2885.1983.tb00450.x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2016.06.015"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12894"},{"issue":"3","key":"e_1_2_11_22_1","first-page":"396","article-title":"Pharmacokinetics of sulfadiazine\/trimethoprim in neonatal male calves: Effect of age and penetration into cerebrospinal fluid","volume":"50","author":"Shoaf S. 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