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 |
|