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Due to biomedical advances, the infants who receive this drug in the neonatal intensive care unit setting have become younger, smaller, and less mature (more preterm) at the time of treatment. To develop a pharmacokinetics (PK) model to aid future dosing, we designed a prospective cohort study to characterize indomethacin PK in a dynamically changing patient population. A population PK base model was created using NONMEM, and a covariate model was developed in a primary development cohort and subsequently was tested for accuracy in a validation cohort. Postnatal age was a significant covariate for hepatic clearance (CL<jats:sub>H<\/jats:sub>) and renal clearance (CL<jats:sub>R<\/jats:sub>). The typical value of the total clearance (CL, the sum of CL<jats:sub>R<\/jats:sub> and CL<jats:sub>H<\/jats:sub>) was 3.09\u2009ml\/h and expressed as CL\/WT<jats:sub>median<\/jats:sub>\u00a0=\u00a03.96\u2009ml\/h\/kg, where WT<jats:sub>median<\/jats:sub> is the median body weight. The intersubject variability of CL<jats:sub>R<\/jats:sub> and CL<jats:sub>H<\/jats:sub> were 61% and 207%, respectively. The typical value of the volume of distribution <jats:italic>V<\/jats:italic><jats:sub>p<\/jats:sub>\u00a0=\u00a0366\u2009ml (<jats:italic>V<\/jats:italic><jats:sub>p<\/jats:sub>\/WT<jats:sub>median<\/jats:sub>\u00a0=\u00a0470\u2009ml\/kg), and its intersubject variability was 38.8%. Half\u2010life was 82.1\u00a0h. Compared with more mature and older preterm populations studied previously, indomethacin CL is considerably lower in this contemporary population. Model\u2010informed precision dosing incorporating important covariates other than weight alone offers an opportunity to individualize dosing in a susceptible patient undergoing rapid change.<\/jats:p>","DOI":"10.1002\/psp4.12881","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T17:48:16Z","timestamp":1667152096000},"page":"110-121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Developmental pharmacokinetics of indomethacin in preterm neonates: Severely decreased drug clearance in the first week of life"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9773-1739","authenticated-orcid":false,"given":"Wojciech","family":"Krzyzanski","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences The State University of New York at Buffalo  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Stockard","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Missouri Kansas City School of Medicine  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gaedigk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Missouri Kansas City School of Medicine  Kansas City Missouri USA"},{"name":"Division of Clinical Pharmacology Toxicology and Therapeutic Innovation, Children's Mercy Hospital  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Scott","sequence":"additional","affiliation":[{"name":"Division of Neonatology Children's Mercy Hospital  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney","family":"Nolte","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Toxicology and Therapeutic Innovation, Children's Mercy Hospital  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Gibson","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Toxicology and Therapeutic Innovation, Children's Mercy Hospital  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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