The need for area under the curve measurements in the field of ganciclovir therapeutic drug monitoring in children: a case report.

Antiviral therapy Cytomegalovirus (CMV) Hematopoietic stem cell transplantation Pediatrics Pharmacokinetics Therapeutic drug monitoring

Journal

BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551

Informations de publication

Date de publication:
08 Nov 2021
Historique:
received: 28 06 2021
accepted: 28 10 2021
entrez: 9 11 2021
pubmed: 10 11 2021
medline: 11 11 2021
Statut: epublish

Résumé

Ganciclovir pharmacokinetics is characterized by a high variability in drug exposure. Usually, monitoring of ganciclovir exposure is performed by measuring trough concentration. However, due to the specificity of pediatric pharmacokinetics, trough concentration measurements may not be a relevant surrogate of ganciclovir exposure. Area under the curve of concentration (AUC) may be a more appropriate biomarker. We report the case of 3.6-year-old boy with Emberger syndrome with a cytomegalovirus reactivation occurring after allogenic hematopoietic stem cell transplantation. After a few days of treatment with intravenous ganciclovir, sub-therapeutic trough ganciclovir concentrations were measured (< 0.5 µg/mL) and viral load still increased. Ganciclovir dosage was increased by two-fold to deal with this treatment failure. Trough concentrations remained sub-therapeutic. The patient had hematologic disorder therefore it was decided to estimate ganciclovir AUC to assess more accurately drug exposure before any further dosage modification. AUC This case report highlights that monitoring ganciclovir exposure based on AUC should be performed to tailor drug dosage in order to improve treatment efficacy and safety in pediatric patients.

Sections du résumé

BACKGROUND BACKGROUND
Ganciclovir pharmacokinetics is characterized by a high variability in drug exposure. Usually, monitoring of ganciclovir exposure is performed by measuring trough concentration. However, due to the specificity of pediatric pharmacokinetics, trough concentration measurements may not be a relevant surrogate of ganciclovir exposure. Area under the curve of concentration (AUC) may be a more appropriate biomarker.
CASE PRESENTATION METHODS
We report the case of 3.6-year-old boy with Emberger syndrome with a cytomegalovirus reactivation occurring after allogenic hematopoietic stem cell transplantation. After a few days of treatment with intravenous ganciclovir, sub-therapeutic trough ganciclovir concentrations were measured (< 0.5 µg/mL) and viral load still increased. Ganciclovir dosage was increased by two-fold to deal with this treatment failure. Trough concentrations remained sub-therapeutic. The patient had hematologic disorder therefore it was decided to estimate ganciclovir AUC to assess more accurately drug exposure before any further dosage modification. AUC
CONCLUSIONS CONCLUSIONS
This case report highlights that monitoring ganciclovir exposure based on AUC should be performed to tailor drug dosage in order to improve treatment efficacy and safety in pediatric patients.

Identifiants

pubmed: 34749667
doi: 10.1186/s12879-021-06828-8
pii: 10.1186/s12879-021-06828-8
pmc: PMC8573890
doi:

Substances chimiques

Antiviral Agents 0
Ganciclovir P9G3CKZ4P5

Types de publication

Case Reports Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1143

Informations de copyright

© 2021. The Author(s).

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Auteurs

Xavier Duval (X)

Laboratory of Clinical Pharmacology, University Hospital of Rennes, 2 Rue Henri le Guilloux, 35000, Rennes, France.

Florian Lemaitre (F)

Laboratory of Clinical Pharmacology, University Hospital of Rennes, 2 Rue Henri le Guilloux, 35000, Rennes, France.
Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail), UMR_S 1085, University of Rennes, 35000, Rennes, France.

Sophie Pertuisel (S)

Department of Paediatric Hemato-Oncology, University Hospital of Rennes, 35000, Rennes, France.

Jamie Probert (J)

Department of Paediatric Hemato-Oncology, University Hospital of Rennes, 35000, Rennes, France.

Virginie Gandemer (V)

Department of Paediatric Hemato-Oncology, University Hospital of Rennes, 35000, Rennes, France.

Marie-Clémence Verdier (MC)

Laboratory of Clinical Pharmacology, University Hospital of Rennes, 2 Rue Henri le Guilloux, 35000, Rennes, France.
Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail), UMR_S 1085, University of Rennes, 35000, Rennes, France.

Camille Tron (C)

Laboratory of Clinical Pharmacology, University Hospital of Rennes, 2 Rue Henri le Guilloux, 35000, Rennes, France. camille.tron@chu-rennes.fr.
Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail), UMR_S 1085, University of Rennes, 35000, Rennes, France. camille.tron@chu-rennes.fr.

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Classifications MeSH