{"id":8905,"date":"2025-11-03T16:37:17","date_gmt":"2025-11-03T15:37:17","guid":{"rendered":"https:\/\/fhu-premimpact.org\/?post_type=publication&#038;p=8905"},"modified":"2025-12-04T16:42:04","modified_gmt":"2025-12-04T15:42:04","slug":"paracetamol-concentrations-and-time-course-of-ductus-arteriosus-diameter-in-extremely-preterm-neonates-a-population-pharmacokinetic-pharmacodynamic-analysis-2","status":"publish","type":"publication","link":"https:\/\/fhu-premimpact.org\/en\/publications\/paracetamol-concentrations-and-time-course-of-ductus-arteriosus-diameter-in-extremely-preterm-neonates-a-population-pharmacokinetic-pharmacodynamic-analysis-2\/","title":{"rendered":"Paracetamol Concentrations and Time-Course of Ductus Arteriosus Diameter in Extremely Preterm Neonates: A Population Pharmacokinetic-Pharmacodynamic Analysis"},"content":{"rendered":"\n<h4 class=\"wp-block-heading\">Abstract<\/h4>\n\n\n\n<p><strong>Background:<\/strong> Patent ductus arteriosus is a common complication of extreme prematurity. Prophylactic treatment with indomethacin or ibuprofen has shown efficacy on ductus closure but without reducing mortality and morbidity. Prophylactic treatment by paracetamol could be a safer alternative.<\/p>\n\n\n\n<p><strong>Objective:<\/strong> The aim was to build a pharmacokinetic-pharmacodynamic (PKPD) model describing the effect of paracetamol on the time-course of the ductus arteriosus diameter.<\/p>\n\n\n\n<p><strong>Methods:<\/strong> Extremely preterm neonates of 23-26 weeks of gestational age were recruited within 12 h after birth and were treated with prophylactic intravenous paracetamol for 5 days (two dose levels: 20 mg\/kg followed by 7.5 mg\/kg or 25 mg\/kg followed by 10 mg\/kg every 6 h). The diameter of ductus arteriosus was determined by echocardiography performed daily until day 7. The PKPD model was built using an I<sub>max<\/sub> model with effect compartment and exponential disease progression model. Concentrations of paracetamol in the effect compartment were simulated with different doses over time for 500 virtual patients.<\/p>\n\n\n\n<p><strong>Results:<\/strong> A total of 29 extremely preterm neonates with median birth weight of 800 g (IQR: 670-860) were included in the study. Between-subject variability was estimated on transfer rate constant between the central compartment and the effect compartment (ke<sub>0<\/sub>) and maximum drug inhibition (I<sub>max<\/sub>) parameters. Two subpopulations with different I<sub>max<\/sub> values were identified: 99% for a first subpopulation of 10 patients and 42% for the second subpopulation of 19 patients. A negative effect of maximum fraction of inspired oxygen (FiO<sub>2<\/sub>) used during transfer to intensive care unit and a positive effect of intubation and ventilation during treatment were significant on ke<sub>0<\/sub>. Simulations showed that both dose levels generally enabled patients to reach the concentration needed to achieve 95% of maximal inhibition by the end of treatment. However, the second dose level enabled more than 90% of patients to reach this inhibition threshold as early as day one.<\/p>\n\n\n\n<p><strong>Conclusion:<\/strong> The relationship between paracetamol and the time-course of ductus arteriosus diameter has been described in extremely preterm neonates. Intravenous paracetamol treatment with a loading dose of 25 mg\/kg within 12 h after birth followed by 10 mg\/kg every 6 h appears to be effective to accelerate time to ductus closure with limited benefit of a further dose increase.<\/p>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Clin Pharmacokinet. 2025 Nov;64(11):1681 -1691. <\/p>\n","protected":false},"featured_media":0,"template":"","class_list":["post-8905","publication","type-publication","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Paracetamol Concentrations and Time-Course of Ductus Arteriosus Diameter in Extremely Preterm Neonates: A Population Pharmacokinetic-Pharmacodynamic Analysis - FHU Prem&#039;IMPACT<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/fhu-premimpact.org\/en\/publications\/paracetamol-concentrations-and-time-course-of-ductus-arteriosus-diameter-in-extremely-preterm-neonates-a-population-pharmacokinetic-pharmacodynamic-analysis-2\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Paracetamol Concentrations and Time-Course of Ductus Arteriosus Diameter in Extremely Preterm Neonates: A Population Pharmacokinetic-Pharmacodynamic Analysis - 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