Population pharmacokinetics of ganciclovir and valganciclovir in paediatric solid organ and stem cell transplant recipients.
children
modelling and simulation
pharmacokinetics
population analysis
transplantation
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
26
11
2020
received:
17
07
2020
accepted:
11
12
2020
pubmed:
30
12
2020
medline:
28
10
2021
entrez:
29
12
2020
Statut:
ppublish
Résumé
Ganciclovir (GCV) and its prodrug valganciclovir (VGCV) are first-line agents to prevent and treat cytomegalovirus in transplant recipients. There is high pharmacokinetic (PK) interindividual variability and PK data are scarce, especially in paediatric stem cell transplant (SCT) recipients. We sought to determine the optimal GCV and VGCV dosing in transplanted children. We conducted a single-centre retrospective population PK (POPPK) study of IV GCV and enteral VGCV in paediatric solid organ transplant (SOT) and SCT recipients. We included children who were transplanted and had available plasma GCV concentrations, done per standard of care. POPPK analysis was performed using a nonlinear mixed effects modelling approach with NONMEM. Optimal dosing was determined based on the achievement of the surrogate efficacy target: GCV 24 h area under the concentration-time curve (AUC Fifty children with a median [range] age of 7.5 years [0.5-17.4] contributed 580 PK samples. A two-compartment model with first-order absorption with a lag time and first-order elimination fit the data well. Creatinine clearance and body weight (WT) were significant covariates for GCV clearance (CL); and WT for the volumes of distribution. IV GCV 15-20 mg.kg This is the first POPPK model developed in children with either SOT or SCT. Concentration target achievement was low, suggesting a potential benefit for therapeutic drug monitoring to ensure optimal exposure.
Substances chimiques
Antiviral Agents
0
Valganciclovir
GCU97FKN3R
Ganciclovir
P9G3CKZ4P5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3105-3114Informations de copyright
© 2020 British Pharmacological Society.
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