{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:26:27Z","timestamp":1787167587202,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007172","name":"Cincinnati Children's Hospital Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007172","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>Aims<\/jats:title>\n                    <jats:p>To develop a population pharmacokinetic (PopPK) model of cefepime in paediatric and young adult BMT patients, identify clinical predictors of variability in cefepime clearance and simulate dosing strategies to optimize therapeutic target attainment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This PopPK analysis pooled data from two prospective studies, including 97 BMT patients aged 1\u2009month to 30\u2009years with 252 cefepime plasma concentrations. The final model was validated with goodness\u2010of\u2010fit plots, bootstrap analysis and prediction\u2010corrected visual predictive checks. Monte Carlo simulations assessed the probability of target attainment (PTA) for various dosing regimens, targeting 100% of the dosing interval during which free drug concentrations exceed the minimum inhibitory concentration (100%\n                      <jats:italic>f<\/jats:italic>\n                      T&gt;MIC), across a range of estimated glomerular filtration rates (eGFR) and MICs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A two\u2010compartment model with first\u2010order elimination best described the data. The most predictive covariate for cefepime clearance was eGFR estimated using a combined creatinine\u2010cystatin C equation (eGFR\n                      <jats:sub>cr\u2010cys<\/jats:sub>\n                      ). Simulations suggested that standard cefepime dosing (50\u2009mg\/kg every 8\u2009h over 30\u2009min) often failed to achieve \u226590% PTA, particularly at MICs \u22652\u20138\u2009mg\/L in patients with normal or augmented renal clearance. Extended (3\u2010hour) or continuous infusions substantially improved PTA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study presents the first cefepime PopPK model tailored to paediatric and young adult BMT recipients, identifying eGFR\n                      <jats:sub>cr\u2010cys<\/jats:sub>\n                      as a key determinant of cefepime clearance. Prolonging the infusion duration or shortening the dosing interval may be required to enhance target attainment with initial dosing regimens. This PopPK model provides a foundation for individualized dosing adjustments through model\u2010informed precision dosing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70519","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T02:04:44Z","timestamp":1773367484000},"page":"2316-2325","source":"Crossref","is-referenced-by-count":1,"title":["Population pharmacokinetics and Monte Carlo simulation of Cefepime in paediatric and Young adult bone marrow transplant patients"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5856-3717","authenticated-orcid":false,"given":"Ronaldo","family":"Morales Junior","sequence":"first","affiliation":[{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1218-8293","authenticated-orcid":false,"given":"H. Rhodes","family":"Hambrick","sequence":"additional","affiliation":[{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati OH USA"},{"name":"Division of Nephrology and Hypertension Cincinnati Children's Hospital Medical Center  Cincinnati OH USA"},{"name":"Division of Nephrology Ann and Robert H. Lurie Children's Hospital of Chicago  Chicago IL USA"},{"name":"Department of Pediatrics Northwestern Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie W.","family":"Benoit","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati OH USA"},{"name":"Division of Bone Marrow Transplantation and Immune Deficiency Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Klink","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Cincinnati Children's Hospital Medical Center  Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8471-9826","authenticated-orcid":false,"given":"Tomoyuki","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati OH USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7737-8499","authenticated-orcid":false,"given":"Sonya","family":"Tang Girdwood","sequence":"additional","affiliation":[{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati OH USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati OH USA"},{"name":"Center for Acute Care Nephrology Cincinnati Children's Hospital Medical Center  Cincinnati OH USA"},{"name":"Division of Hospital Medicine, Department of Pediatrics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409\u2010019\u20100624\u2010z"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis210"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2014.235"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2023.106368"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir073"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010022\u201001137\u2010y"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2505"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad223"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2024.03.021"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bcp.70120"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2018.07.005"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1044683"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1773"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094708"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010200847040\u201000002"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.01640309"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2102953"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.10.047"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12611"},{"key":"e_1_2_11_21_1","unstructured":"NHANES Questionnaires Datasets and Related Documentation. Accessed February 6 2024.https:\/\/wwwn.cdc.gov\/nchs\/nhanes\/"},{"key":"e_1_2_11_22_1","volume-title":"M02 standard","author":"CLSI","year":"2024"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.4103\/jtccm.jtccm_21_20"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010025\u201001485\u20105"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.04.008"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1807"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlac043"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.018"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2016.11.016"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00389\u201015"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.777854"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.5863\/1551\u20106776\u201026.2.187"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00787\u201015"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70519","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70519","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70519","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:33:51Z","timestamp":1784097231000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":32,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/bcp.70519"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70519","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]}}}