New algorithm for valganciclovir dosing in pediatric solid organ transplant recipients

作者：A**erg A^*; Bjerre A; Neely M

来源：Pediatric Transplantation, 2014, 18(1): 103-111.

DOI：10.1111/petr.12179

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

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 0.3-16.9yr 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 40-60mg*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 GFR30mL/min, k=10 for GFR>30mL/min and weight>30kg and k=15 for GFR>30mL/min and weight30kg, outperformed the other algorithms. Thirty-three percent of all patients achieve an exposure above and 21% within the therapeutic 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

• 出版日期2014-2