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Pediatr Transplant. 2014 Feb;18(1):103-11. doi: 10.1111/petr.12179. Epub 2013 Oct 23.

New algorithm for valganciclovir dosing in pediatric solid organ transplant recipients.

Author information

1
Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.

Abstract

CMV infections are common after SOT. v-GCV is increasingly used in children. The aim of this study was to evaluate presently used dosing algorithms. Data from 104 pediatric SOT recipients (kidney, liver, and heart) aged 0.3-16.9 yr and receiving v-GCV once a day were used for model development and validation with the Pmetrics package for R. Monte Carlo simulations were performed to compare the probability of a GCV AUC 40-60 mg*h/L with the different algorithms across a range of ages, weights, and GFRs. GCV pharmacokinetics was well described by the non-parametric model. Clearance was dependent on GFR and Cockcroft-Gault estimates improved the model fit over Schwartz. Simulations showed that our new algorithm, where v-GCV dose is: Weight [kg]*(0.07*GFR [mL/min]+k), where k = 5 for GFR ≤ 30 mL/min, k = 10 for GFR > 30 mL/min and weight > 30 kg and k = 15 for GFR > 30 mL/min and weight ≤ 30 kg, outperformed the other algorithms. Thirty-three percent of all patients achieve an exposure above and 21% within the therapeutic window. We propose a simple algorithm for initial v-GCV dosing that standardizes plasma drug exposure better than current algorithms. Subsequent TDM is strongly suggested to achieve individual drug levels within the therapeutic window.

KEYWORDS:

cytomegalovirus; pediatric transplantation; population model; solid organ transplantation; therapeutic drug monitoring; valganciclovir

PMID:
24152053
PMCID:
PMC3880615
DOI:
10.1111/petr.12179
[Indexed for MEDLINE]
Free PMC Article

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