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The pharmacokinetics of valganciclovir prophylaxis in pediatric solid organ transplant patients at risk for Epstein–Barr virus disease

Antiviral prophylaxis with valganciclovir is used frequently in pediatric solid organ transplant patients to prevent Epstein–Barr virus (EBV)-induced infections and tissue-invasive disease including post-transplant lymphoproliferative disorder (PTLD). This approach is untested in clinical trials and...

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Autores principales: Vezina, Heather E, Brundage, Richard C, Nevins, Thomas E, Balfour, Henry H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262369/
https://www.ncbi.nlm.nih.gov/pubmed/22291482
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author Vezina, Heather E
Brundage, Richard C
Nevins, Thomas E
Balfour, Henry H
author_facet Vezina, Heather E
Brundage, Richard C
Nevins, Thomas E
Balfour, Henry H
author_sort Vezina, Heather E
collection PubMed
description Antiviral prophylaxis with valganciclovir is used frequently in pediatric solid organ transplant patients to prevent Epstein–Barr virus (EBV)-induced infections and tissue-invasive disease including post-transplant lymphoproliferative disorder (PTLD). This approach is untested in clinical trials and valganciclovir dosing strategies in children are highly variable. Our objective was to characterize the pharmacokinetics of ganciclovir in the plasma of pediatric kidney and liver transplant patients taking valganciclovir for EBV prophylaxis. Virologic response was also evaluated. Ganciclovir was measured by liquid chromatography/ultraviolet detection. EBV DNA was quantified by TaqMan(®) polymerase chain reaction. NONMEM(®) VI was used for data analysis. Ganciclovir plasma profiles were consistent with a one-compartment model. Final model estimates of apparent oral clearance (L/h), apparent volume of distribution (L), and absorption rate constant were 7.33, 35.1, and 0.85, respectively. There was evidence of lower bioavailability in children younger than three years. All eight subjects achieved ganciclovir plasma concentrations above reported in vitro concentrations needed to inhibit EBV replication by 50%. However, four subjects had detectable EBV DNA with a median (range) of 18,300 (4,400 to 54,900) copies/mL of whole blood. These findings support the need for further studies of the clinical pharmacology and efficacy of valganciclovir for EBV prophylaxis.
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spelling pubmed-32623692012-01-30 The pharmacokinetics of valganciclovir prophylaxis in pediatric solid organ transplant patients at risk for Epstein–Barr virus disease Vezina, Heather E Brundage, Richard C Nevins, Thomas E Balfour, Henry H Clin Pharmacol Original Research Antiviral prophylaxis with valganciclovir is used frequently in pediatric solid organ transplant patients to prevent Epstein–Barr virus (EBV)-induced infections and tissue-invasive disease including post-transplant lymphoproliferative disorder (PTLD). This approach is untested in clinical trials and valganciclovir dosing strategies in children are highly variable. Our objective was to characterize the pharmacokinetics of ganciclovir in the plasma of pediatric kidney and liver transplant patients taking valganciclovir for EBV prophylaxis. Virologic response was also evaluated. Ganciclovir was measured by liquid chromatography/ultraviolet detection. EBV DNA was quantified by TaqMan(®) polymerase chain reaction. NONMEM(®) VI was used for data analysis. Ganciclovir plasma profiles were consistent with a one-compartment model. Final model estimates of apparent oral clearance (L/h), apparent volume of distribution (L), and absorption rate constant were 7.33, 35.1, and 0.85, respectively. There was evidence of lower bioavailability in children younger than three years. All eight subjects achieved ganciclovir plasma concentrations above reported in vitro concentrations needed to inhibit EBV replication by 50%. However, four subjects had detectable EBV DNA with a median (range) of 18,300 (4,400 to 54,900) copies/mL of whole blood. These findings support the need for further studies of the clinical pharmacology and efficacy of valganciclovir for EBV prophylaxis. Dove Medical Press 2009-12-22 /pmc/articles/PMC3262369/ /pubmed/22291482 Text en © 2010 Vezina et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
Vezina, Heather E
Brundage, Richard C
Nevins, Thomas E
Balfour, Henry H
The pharmacokinetics of valganciclovir prophylaxis in pediatric solid organ transplant patients at risk for Epstein–Barr virus disease
title The pharmacokinetics of valganciclovir prophylaxis in pediatric solid organ transplant patients at risk for Epstein–Barr virus disease
title_full The pharmacokinetics of valganciclovir prophylaxis in pediatric solid organ transplant patients at risk for Epstein–Barr virus disease
title_fullStr The pharmacokinetics of valganciclovir prophylaxis in pediatric solid organ transplant patients at risk for Epstein–Barr virus disease
title_full_unstemmed The pharmacokinetics of valganciclovir prophylaxis in pediatric solid organ transplant patients at risk for Epstein–Barr virus disease
title_short The pharmacokinetics of valganciclovir prophylaxis in pediatric solid organ transplant patients at risk for Epstein–Barr virus disease
title_sort pharmacokinetics of valganciclovir prophylaxis in pediatric solid organ transplant patients at risk for epstein–barr virus disease
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262369/
https://www.ncbi.nlm.nih.gov/pubmed/22291482
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