{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:08:53Z","timestamp":1784099333096,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010804","name":"Faculty of Medicine, Prince of Songkla University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Appropriate drug exposure is as crucial as proper selection and timely antibiotic administration in sepsis treatment. However, evidence is lacking regarding the current dosing regimen to achieve pharmacodynamic targets. This study aimed to describe ceftriaxone pharmacokinetic (PK) parameters and establish optimal dosing regimens for sepsis patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study investigated the pharmacokinetics of ceftriaxone in sepsis patients receiving ceftriaxone 2\u2009g every 12 or 24\u2009h. Blood samples (11\u201314 samples per patient) were collected within the first 24\u2009h post\u2010administration. PK parameters were estimated from unbound plasma concentrations using a nonlinear mixed\u2010effects modelling approach (NONMEM\u00ae software). Monte Carlo simulations were conducted to evaluate the probability of target attainment of standard and high\u2010dose ceftriaxone at various minimum inhibitory concentrations (MICs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Population PK analysis of 238 concentration\u2013time data points from 20 patients revealed that a two\u2010compartment model best described ceftriaxone PK. Glomerular filtration rate (GFR), serum albumin, and body weight significantly affected clearance, volume of distribution, and intercompartmental clearance, respectively. Simulation demonstrated that standard dose of 2\u2009g every 24\u2009h was adequate for pathogens with MIC \u22641\u00a0mg\u2009L\n                      <jats:sup>\u22121<\/jats:sup>\n                      . At higher MIC values, target attainment decreased, particularly in with GFR\u2009&gt;\u2009130\u2009mL\u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      , with twice\u2010daily dosing yielding higher exposures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Standard ceftriaxone (2\u00a0g intravenous q 24\u2009h, 30\u2010min infusion) provided adequate target attainment at low MICs in this exploratory study of suspected sepsis. PTA decreased with higher MICs and higher renal function, with higher dose regimens showing numerically greater exposures. These findings may help guide future studies on dosing optimization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70480","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T07:26:51Z","timestamp":1770708411000},"page":"2095-2108","source":"Crossref","is-referenced-by-count":0,"title":["High\u2010dose ceftriaxone: Pharmacokinetic and pharmacodynamic insights in hospitalized patients with suspected sepsis in Thailand"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4250-9484","authenticated-orcid":false,"given":"Nattapat","family":"Sangkakul","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine Prince of Songkla University  Hat Yai Songkhla Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6169-0039","authenticated-orcid":false,"given":"Apinya","family":"Boonpeng","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacy, Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences University of Phayao  Muang District Phayao Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-3566","authenticated-orcid":false,"given":"Pisud","family":"Siripaitoon","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine Prince of Songkla University  Hat Yai Songkhla Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6929-2089","authenticated-orcid":false,"given":"Narongdet","family":"Kositpantawong","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine Prince of Songkla University  Hat Yai Songkhla Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6311-7463","authenticated-orcid":false,"given":"Siripen","family":"Kanchanasuwan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine Prince of Songkla University  Hat Yai Songkhla Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8115-3955","authenticated-orcid":false,"given":"Sorawit","family":"Chittrakarn","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine Prince of Songkla University  Hat Yai Songkhla Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9938-9199","authenticated-orcid":false,"given":"Monchana","family":"Jullangkoon","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine Prince of Songkla University  Hat Yai Songkhla Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boonsri","family":"Charoenmak","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine Prince of Songkla University  Hat Yai Songkhla Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3116-2518","authenticated-orcid":false,"given":"Sarunyou","family":"Chusri","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine Prince of Songkla University  Hat Yai Songkhla Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134\u2010021\u201006506\u2010y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000217961.75225.E9"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11070899"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495\u2010200262070\u201000005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.34172\/ajcmi.2022.3427"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/516284"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/10895960\u2010000000000\u201000000"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa399"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/11539220\u2010000000000\u201000000"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02189\u201021"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky071"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa067"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02134\u201018"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.20.5.634"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.22.5.816"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15819"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.5414\/CP204181"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2011.04005.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2025.107461"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1415236"},{"key":"e_1_2_10_22_1","unstructured":"Center for Drug Evaluation and Research Center for Veterinary Medicine.Bioanalytical method validation guidance for industry [Internet].2020. FDA. Retrieved April 24 2025.https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/bioanalytical-method"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01427\u201021"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.833189"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000494"},{"issue":"1","key":"e_1_2_10_26_1","first-page":"S1","article-title":"The concise guide to pharmacology 2021\/22","volume":"178","author":"Alexander SPH","year":"2021","journal-title":"Br J Pharmacol"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmmb.2023.100432"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/47.4.421"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01711224"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2016.09.021"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12028\u2010024\u201002144\u20106"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac209"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70480","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70480","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70480","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:33:57Z","timestamp":1784097237000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70480"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":31,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/bcp.70480"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70480","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]}}}