Abstract
Valganciclovir, the ganciclovir prodrug, is an antiviral agent used to prevent cytomegalovirus infection in renal transplant children. Therapeutic drug monitoring is still necessary to ensure optimal therapeutic area under the concentration-time curve from 0 to 24 h (AUC(0-24)) of 40 to 60 μg·h/mL since valganciclovir presents a high pharmacokinetic variability. To calculate ganciclovir AUC(0-24) with the trapezoidal method, 7 samples are needed. The objective of this study was to develop and validate a reliable and clinically applicable limited sampling strategy (LSS) for individualizing valganciclovir dose in renal transplant children. Rich pharmacokinetic data from ganciclovir plasmatic dosages measured in renal transplant children who received valganciclovir to prevent cytomegalovirus infection at Robert Debré University Hospital were collected retrospectively. Ganciclovir AUC(0-24)s were calculated using the trapezoidal method. The LSS was developed using a multilinear regression approach to predict AUC(0-24). The patients included were divided into two groups for model development (50 patients) and validation (30 patients). A total of 80 patients were included between February 2005 and November 2018. Multilinear regression models were developed on 50 pharmacokinetic profiles (50 patients) and validated with an independent group of 43 pharmacokinetic profiles (30 patients). Regressions based on samples collected at T1h-T4h-T8h, T2h-T4h-T8h, or T1h-T2h-T8h presented the best AUC(0-24) predictive performances with an average difference between reference and predicted AUC(0-24) of -0.27, 0.34, and -0.40 μg·h/mL, respectively. In conclusion, valganciclovir dosage adaptation was required in children to achieve the target AUC(0-24). Three LSS models using three pharmacokinetic blood samples instead of seven will be useful for individualizing valganciclovir prophylaxis in renal transplant children.