dc.contributor.author |
Holford, Nick |
|
dc.contributor.author |
O'Hanlon, Conor J |
|
dc.contributor.author |
Allegaert, Karel |
|
dc.contributor.author |
Anderson, Brian |
|
dc.contributor.author |
Falcão, Amilcar |
|
dc.contributor.author |
Simon, Nicolas |
|
dc.contributor.author |
Lo, Yoke-Lin |
|
dc.contributor.author |
Thomson, Alison H |
|
dc.contributor.author |
Sherwin, Catherine M |
|
dc.contributor.author |
Jacqz-Aigrain, Evelyne |
|
dc.contributor.author |
Llanos-Paez, Carolina |
|
dc.contributor.author |
Hennig, Stefanie |
|
dc.contributor.author |
Mockus, Linas |
|
dc.contributor.author |
Kirkpatrick, Carl |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2024-01-10T00:54:31Z |
|
dc.date.available |
2024-01-10T00:54:31Z |
|
dc.date.issued |
2023-11 |
|
dc.identifier.citation |
(2023). British Journal of Clinical Pharmacology. Online Version of Record before inclusion in an issue |
|
dc.identifier.issn |
0306-5251 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/67154 |
|
dc.description.abstract |
Aims:
We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance.
Methods:
Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age, and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution.
Results:
This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non-GFR clearance not associated with normal GFR.
All three drugs had GFR clearance estimated as a drug specific percentage of normal GFR (gentamicin 39%, amikacin 90%, vancomycin 57%).
The total clearance (sum of GFR and non-GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% CI 5.50-5.69) (gentamicin), 7.77 L/h (95 %CI 7.26-8.19) (amikacin) and 4.70 L/h (95 %CI 4.61-4.80) (vancomycin).
Conclusion:
GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention. |
|
dc.format.medium |
Print-Electronic |
|
dc.language |
eng |
|
dc.publisher |
Wiley |
|
dc.relation.ispartofseries |
British journal of clinical pharmacology |
|
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 |
clinical pharmacology |
|
dc.subject |
infectious diseases paediatrics |
|
dc.subject |
nephrology |
|
dc.subject |
pharmacometrics |
|
dc.subject |
32 Biomedical and Clinical Sciences |
|
dc.subject |
3202 Clinical Sciences |
|
dc.subject |
Clinical Research |
|
dc.subject |
Kidney Disease |
|
dc.subject |
1115 Pharmacology and Pharmaceutical Sciences |
|
dc.subject |
3214 Pharmacology and pharmaceutical sciences |
|
dc.title |
A Physiological Approach to Renal Clearance - from Premature Neonates to Adults |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1111/bcp.15978 |
|
dc.date.updated |
2023-12-16T22:27:00Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
38031322 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/38031322 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Journal Article |
|
pubs.elements-id |
1001926 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
Medical Sciences |
|
pubs.org-id |
Pharmacology |
|
dc.identifier.eissn |
1365-2125 |
|
pubs.record-created-at-source-date |
2023-12-17 |
|
pubs.online-publication-date |
2023-11-29 |
|