title: New algorithm for valganciclovir dosing in pediatric solid organ transplant recipients.
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.
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Åsberg
authors.forename: A
authors.initials: A
authors.lastname: Bjerre
authors.forename: M
authors.initials: M
authors.lastname: Neely
mesh_terms: D000293:Adolescent; D000465:Algorithms; D000998:Antiviral Agents / Q000008:administration & dosage*; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005919:Glomerular Filtration Rate; D006801:Humans; D007223:Infant; D008297:Male; D008962:Models, Theoretical; D009010:Monte Carlo Method; D016377:Organ Transplantation / Q000379:methods*; D011336:Probability; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir
keywords: cytomegalovirus; pediatric transplantation; population model; solid organ transplantation; therapeutic drug monitoring; valganciclovir