Unraveling the Contribution of Fluid Therapy to the Development of Augmented Renal Clearance in a Piglet Model.

amikacin augmented renal clearance fluid therapy iohexol large animal model para-aminohippuric acid piglet

Journal

Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923

Informations de publication

Date de publication:
2020
Historique:
received: 16 09 2020
accepted: 14 12 2020
entrez: 12 2 2021
pubmed: 13 2 2021
medline: 13 2 2021
Statut: epublish

Résumé

Augmented renal clearance (ARC) observed in the critically ill pediatric population has received an increased attention over the last years due to its major impact on the disposition and pharmacokinetics of mainly renally excreted drugs. Apart from an important inflammatory trigger, fluid administration has been suggested to contribute to the development of ARC. Therefore, the primary objective of this study was to evaluate the effect of continuous intravenous fluid administration on renal function using a conventional piglet animal model and to quantify the impact of fluid administration on the pharmacokinetics of renally excreted drugs. At baseline, twenty-four piglets (12 treatment/12 control; 7 weeks old, all ♂) received the marker drugs iohexol (64.7 mg/kg body weight (BW)) and para-aminohippuric acid (10 mg/kg BW) to quantify glomerular filtration rate and effective renal plasma flow, respectively. In addition, the hydrophilic antibiotic amikacin (7.5 mg/kg BW) was administered. Following this baseline measurement, the treatment group received fluid therapy as a constant rate infusion of 0.9% saline at 6 mL/kg/h over 36 h. After 24 h of fluid administration, the marker drugs and amikacin were administered again. When comparing both groups, a significant effect of fluid administration on the total body clearances of iohexol (

Identifiants

pubmed: 33574754
doi: 10.3389/fphar.2020.607101
pii: 607101
pmc: PMC7870502
doi:

Types de publication

Journal Article

Langues

eng

Pagination

607101

Informations de copyright

Copyright © 2021 Dhondt, Croubels, De Paepe, Goethals, De Cock and Devreese.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Laura Dhondt (L)

Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Siska Croubels (S)

Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Peter De Paepe (P)

Heymans Institute of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.

Klara Goethals (K)

Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Pieter De Cock (P)

Heymans Institute of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Department of Pharmacy, Ghent University Hospital, Ghent, Belgium.
Department of Paediatric Intensive Care, Ghent University Hospital, Ghent, Belgium.

Mathias Devreese (M)

Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Classifications MeSH