{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:10:40Z","timestamp":1779970240177,"version":"3.53.1"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Furosemide is the most commonly used diuretic in preterm infants despite an incompletely understood relationship between dosing, exposure, and safety within this population. The goals of this study were to characterize furosemide population pharmacokinetics (popPK) in preterm infants and to evaluate safety by relating simulated furosemide exposure to events of ototoxicity, nephrocalcinosis, and nephrolithiasis. A total of 146 plasma furosemide concentrations from 51 preterm (23\u201028.9 weeks\u2019 gestational age) infants across two studies (one randomized, placebo\u2010controlled, dose\u2010escalating safety trial and one opportunistic, observational study) were included in the analysis. Standard nonlinear mixed effects popPK modeling techniques were applied. Exposure was simulated using the final popPK model (area under the curve) and Monte Carlo simulations (maximum concentration [C\n                    <jats:sub>max<\/jats:sub>\n                    ]). Logistic regression was used to evaluate the relationship between exposure and safety events. The final popPK model was a one\u2010compartment model with the covariates of weight on volume of distribution and both weight and post\u2010natal age on clearance. The model showed accurate predictions, adequate precision, and good model fit. Simulations indicated that furosemide 2 mg\/kg administered enterally every 6 h would result in few (approximately 4%) C\n                    <jats:sub>max<\/jats:sub>\n                    values exceeding a 50 \u00b5g\/mL threshold reported to be associated with treatment\u2010associated ototoxicity, and no more than 1% for all other dosing regimens. Events of hearing loss, nephrocalcinosis, or nephrolithiasis were rare and showed no relationship with furosemide exposure in logistic regression analysis. These data contributed to the October 2024 FDA label update to include pediatric popPK data and improve dosing in preterm infants.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70186","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T05:56:02Z","timestamp":1776664562000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics and Exposure\u2010Safety Analysis of Furosemide in Preterm Infants"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8009-8209","authenticated-orcid":false,"given":"Rachel L.","family":"Randell","sequence":"first","affiliation":[{"name":"Department of Pediatrics Duke University  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Maharaj","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute  Durham NC USA"},{"name":"Faculty of Pharmaceutical Sciences The University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Laughon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi D.","family":"Hornik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel G.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9115-5312","authenticated-orcid":false,"given":"Jason E.","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cohen\u2010Wolkowiez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph P.","family":"Hornik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University  Durham NC USA"},{"name":"Duke Clinical Research Institute  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinder","family":"Anand","sequence":"additional","affiliation":[{"name":"The Emmes Company  Rockville MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Martz","sequence":"additional","affiliation":[{"name":"The Emmes Company  Rockville MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0905-7647","authenticated-orcid":false,"given":"Elizabeth H.","family":"Payne","sequence":"additional","affiliation":[{"name":"The Emmes Company  Rockville MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Watt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Utah  Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7690-0695","authenticated-orcid":false,"given":"William J.","family":"Muller","sequence":"additional","affiliation":[{"name":"Ann &amp; Robert H. Lurie Children's Hospital of Chicago  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry E.","family":"Courtney","sequence":"additional","affiliation":[{"name":"Arkansas Children's Hospital  Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Atz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Medical University of South Carolina  Charleston SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6532-7117","authenticated-orcid":false,"given":"Amira","family":"Al\u2010Uzri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Oregon Health &amp; Science University  Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M.","family":"Sokol","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Indiana University School of Medicine  Indianapolis IN 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