Abstract
【Objective】Ganciclovir (GCV) and valganciclovir (VGCV) are used for the treatment and preemptive therapy of cytomegalovirus infection in pediatric liver transplantation patients. A GCV 24-hour area under the time-concentration curve (AUC0-24) of 40 – 60 μg/mL⋅hr is related to efficacy. The primary objective was to compare systemic exposures of GCV in patients administered GCV or VGCV using AUC0-24. Secondary objectives were the evaluation of causal relationships between AUC0-24 and efficacy or adverse effects.
【Study Design】Retrospective case series study.
【Methods】A limited sampling strategy was used to estimate AUC0-24. The time to a clearance of pp65 antigenemia was used as an efficacy, and incidences of renal and hematological toxicity were used as a safety.
【Results】Twenty-two pediatric liver transplantation patients were enrolled in the study. Estimated AUC0-24 using 2 sampling times (2 – 3 and 6 – 8 hours after administration) showed a good predictive performance by the Bayesian approaches. Ten patients were included in the AUC0-24 equivalence study and the mean AUC0-24 ratio (VGCV/GCV) was 1.04. In this study, a higher inter-individual variability in AUC0-24 was observed after VGCV administration. In efficacy evaluation, a slower clearance of pp65 antigenemia was observed in patients with AUC0-24 of less than 40. Incidences of renal and hematological toxicity tend to be higher in patients with AUC0-24 more than 60, although not significant differences were noted between AUC0-24 groups.
【Conclusions】In this study, the systemic exposure of GCV following VGCV and GCV administration was equivalent. Lower exposure may cause prolongation of the dosing period, and long-term administration threatens patients with renal and hematological toxicity.
