Model-based Dosage Individualization of Ganciclovir in Neonates and Young Infants with Congenital Cytomegalovirus Infection: A Pilot Study [PublishAheadOfPrint]

Background: Newborns with congenital cytomegalovirus (CMV) infection are at high risk for developing permanent sequelae. Intravenous ganciclovir therapy is frequently used for the treatment of congenital CMV infection. Target area under the concentration versus time curve (AUC_0–24) of 40-50 μg·h/mL is recommended. The standard dose resulted in a large variability in ganciclovir exposure in newborns, indicating the unmet need of dosage individualization in this vulnerable population, but the implementation of this strategy remains challenging in clinical practice. We aim to evaluate the clinical utility of model-based dosage individualization of ganciclovir in newborns using an opportunistic sampling approach.

Methods: The predictive performance of a published ganciclovir population pharmacokinetic model was evaluated using an independent patient cohort. The individual dose was adjusted based on the target AUC_0-24 to ensure the efficacy.

Results: A total of 26 newborns with congenital CMV infection were included in the present study. Only 11 (42.3%) patients achieved the target AUC_0-24 after giving the standard dose. For all the subtherapeutic (below 80% target AUC) patients (n=5), model-based dosage adjustment was performed using Bayesian estimation method combined with the opportunistic sampling strategy. The adjusted doses were increased 28.6% - 60.0% in these five patients and all adapted AUC_0–24 achieved the target (range: 48.6-66.1 μg·h/mL).

Conclusion: The clinical utility of model-based dosing individualization of ganciclovir was demonstrated in newborns with congenital CMV infection. Population pharmacokinetic model combined with the opportunistic sampling strategy provides a clinical feasible method to adapt ganciclovir dose in neonatal clinical practice.

http://ift.tt/2D273Qr