Time-Varying Clearance in Milrinone Pharmacokinetics from Premature Neonates to Adolescents.

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dc.contributor.author O'Hanlon, Conor J
dc.contributor.author Sumpter, Anita
dc.contributor.author Anderson, Brian J
dc.contributor.author Hannam, Jacqueline A
dc.coverage.spatial Switzerland
dc.date.accessioned 2024-05-08T22:15:29Z
dc.date.available 2024-05-08T22:15:29Z
dc.date.issued 2024-04
dc.identifier.citation (2024). Clinical Pharmacokinetics, 1-12.
dc.identifier.issn 0312-5963
dc.identifier.uri https://hdl.handle.net/2292/68332
dc.description.abstract <h4>Background and objectives</h4>Milrinone is an inotrope and vasodilator used for prophylaxis or treatment of low cardiac output syndrome after weaning from cardiopulmonary bypass (CPB). It is renally eliminated and has an acceptable therapeutic range of 100-300 μg/L, but weight-based dosing alone is associated with poor target attainment. We aimed to develop a population pharmacokinetic model for milrinone from premature neonates to adolescents, and to evaluate how age, renal function and recovery from CPB may impact dose selection.<h4>Methods</h4>Fifty paediatric patients (aged 4 days to 16 years) were studied after undergoing cardiac surgery supported by CPB. Data from 29 premature neonates (23-28 weeks' postmenstrual age) treated for prophylaxis of low systemic blood flow were available for a pooled pharmacokinetic analysis. Population parameters were estimated using non-linear mixed effects modelling (NONMEM 7.5.1).<h4>Results</h4>There were 369 milrinone measurements available for analysis. A one-compartment model with zero-order input and first-order elimination was used to describe milrinone disposition. Population parameters were clearance 17.8 L/70 kg [95% CI 15.8-19.9] and volume 20.4 L/h/70 kg [95% CI 17.8-22.1]. Covariates included size, postmenstrual age and renal function for clearance, and size and postnatal age for volume. Milrinone clearance is reduced by 39.5% [95% CI 24.0-53.7] immediately after bypass, and recovers to baseline clearance with a half-time of 12.0 h [95% CI 9.7-15.2]. Milrinone volume was 2.07 [95% CI 1.87-2.27] times greater at birth than the population standard and decreased over the first days of life with a half-time of 0.977 days [95% CI 0.833-1.12].<h4>Conclusion</h4>Milrinone is predominately renally eliminated and so renal function is an important covariate describing variability in clearance. Increasing clearance over time likely reflects increasing cardiac output and renal perfusion due to milrinone and return to baseline following CPB.
dc.format.medium Print-Electronic
dc.language eng
dc.publisher Springer Nature
dc.relation.ispartofseries Clinical pharmacokinetics
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
dc.subject 32 Biomedical and Clinical Sciences
dc.subject 3202 Clinical Sciences
dc.subject Pediatric Research Initiative
dc.subject Pediatric
dc.subject Cardiovascular
dc.subject Rehabilitation
dc.subject Kidney Disease
dc.subject Science & Technology
dc.subject Life Sciences & Biomedicine
dc.subject Pharmacology & Pharmacy
dc.subject CARDIAC-OUTPUT SYNDROME
dc.subject PEDIATRIC-PATIENTS
dc.subject INTRAVENOUS PHARMACOKINETICS
dc.subject KIDNEY INJURY
dc.subject CHILDREN
dc.subject SURGERY
dc.subject INFANTS
dc.subject QUANTIFICATION
dc.subject CLONIDINE
dc.subject BYPASS
dc.subject 1115 Pharmacology and Pharmaceutical Sciences
dc.subject 3214 Pharmacology and pharmaceutical sciences
dc.title Time-Varying Clearance in Milrinone Pharmacokinetics from Premature Neonates to Adolescents.
dc.type Journal Article
dc.identifier.doi 10.1007/s40262-024-01372-5
pubs.begin-page 1
dc.date.updated 2024-04-28T04:47:46Z
dc.rights.holder Copyright: The authors en
dc.identifier.pmid 38613610 (pubmed)
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/38613610
pubs.end-page 12
pubs.publication-status Published
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype Journal Article
pubs.elements-id 1023441
pubs.org-id Medical and Health Sciences
pubs.org-id Medical Sciences
pubs.org-id Pharmacology
pubs.org-id School of Medicine
pubs.org-id Anaesthesiology
dc.identifier.eissn 1179-1926
dc.identifier.pii 10.1007/s40262-024-01372-5
pubs.record-created-at-source-date 2024-04-28
pubs.online-publication-date 2024-04-13


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