Open AccessPediatric Dosing of Ganciclovir and Valganciclovir: How Model‐Based Simulations Can Prevent Underexposure and Potential Treatment Failure
Author(s) -
Jorga Karin,
Reigner Bruno,
Chavanne Clarisse,
Alvaro Giuseppe,
Frey Nicolas
Publication year - 2019
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12363
Subject(s) - dosing , valganciclovir , ganciclovir , medicine , pharmacokinetics , cmax , body surface area , human cytomegalovirus , immunology , virus
Intravenous ganciclovir and oral valganciclovir are effective in the prevention and treatment of pediatric cytomegalovirus ( CMV ) infection but various dosing regimens are used in medical practice. Population pharmacokinetic (PopPK) model‐based simulations were used to propose a new ganciclovir pediatric dosing algorithm for regulatory review and to evaluate the approved valganciclovir pediatric dosing algorithm against published dosing recommendations derived from quantitative approaches. Oral valganciclovir (mg = 7 × body surface area ( BSA ) × creatinine clearance according to the Schwarz formula (Cr CLS ) daily) and i.v. ganciclovir (mg = 3 × BSA × Cr CLS daily) are effective in reaching ganciclovir target exposure for the prevention of CMV (area under the concentration‐time curve ( AUC ) 0–24 40–60 μg ∙ hour/ mL ) in most pediatric patients across the full pediatric age range. In contrast, ganciclovir and valganciclovir dosing based on body weight, as commonly used in medical practice, leads to underexposure, particularly in younger pediatric patients. This example shows that model‐based dosing algorithms built on clinical pharmacology and implemented using good modeling practice can prevent underexposure and reduce the risk of treatment failure in pediatric patients.