{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T21:52:31Z","timestamp":1777585951104,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The use of indomethacin to delay delivery in preterm labor (PTL) is widely accepted; however, the optimal dosage of indomethacin in pregnancy is unknown. Here, we perform population pharmacokinetic (PK) and pharmacodynamic (PD) analyses, characterize the plasma disposition of indomethacin in pregnant women with PTL, and relate indomethacin exposure to delayed delivery and maternal\/neonatal safety. We analyzed plasma and urine samples collected from a multicenter, prospective, opportunistic PK\/PD study of indomethacin in pregnant women 12\u201032 weeks gestation admitted with PTL. Ninety\u2010four participants with 639 plasma concentrations for indomethacin were included in the analysis. The final population PK (popPK) model for indomethacin was a 2\u2010compartment structural model with first\u2010order absorption and elimination and a covariate effect of body mass index on apparent oral clearance. We observed a 21%\u201060% increase in apparent oral clearance observed during pregnancy. There was no clear association between indomethacin exposure and maternal or neonatal safety outcomes, or with the magnitude of delayed delivery; however, 96.7% of women treated with indomethacin had a delivery that was delayed at least 48 hours. Given the changes to indomethacin apparent oral clearance during pregnancy, and the lack of relationship between indomethacin exposure and safety, dose\u2010finding studies of indomethacin in pregnant women with PTL may help clarify the most safe and efficacious dosage and duration of indomethacin.<\/jats:p>","DOI":"10.1002\/jcph.2412","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T07:16:50Z","timestamp":1707290210000},"page":"728-736","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Indomethacin Pharmacokinetics and Pharmacodynamics in Pregnancies With Preterm Labor: The Need for Dose\u2010Ranging Trials"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-1680","authenticated-orcid":false,"given":"Stephen J.","family":"Balevic","sequence":"first","affiliation":[{"name":"Department of Pediatrics Duke University  Durham NC USA"},{"name":"Duke Clinical Research Institute Duke University  Durham NC USA"},{"name":"Department of Medicine Duke University  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Weiner","sequence":"additional","affiliation":[{"name":"Department of Medicine Duke University  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph P.","family":"Hornik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University  Durham NC USA"},{"name":"Duke Clinical Research Institute Duke University  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Cohen\u2010Wolkowiez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University  Durham NC USA"},{"name":"Duke Clinical Research Institute Duke University  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Duke University  Durham NC USA"},{"name":"Department of Medicine Duke University  Durham NC USA"},{"name":"Division of Pharmacotherapy and Experimental Therapeutics The University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The University of Texas Medical Branch  Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meixiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The University of Texas Medical Branch  Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherif Z.","family":"Abdel\u2010Rahman","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The University of Texas Medical Branch  Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Rytting","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The University of Texas Medical Branch  Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e31825af2f0"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(91)90569-D"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(93)90138-9"},{"issue":"4","key":"e_1_2_10_5_1","first-page":"567","article-title":"Efficacy and safety of indomethacin versus ritodrine in the management of preterm labor: a randomized study","volume":"74","author":"Morales WJ","year":"1989","journal-title":"Obstet Gynecol"},{"key":"e_1_2_10_6_1","unstructured":"Ayurax LLC.Indomethacin capsule [package insert]. 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