title: Valganciclovir dosing using area under the curve calculations in pediatric solid organ transplant recipients.
abstract: Pediatric valganciclovir dosing recommendations have not been extensively validated for prevention or treatment for CMV infection. As such, we performed a pharmacokinetic study to compare different valganciclovir dosing regimens and the potential benefits of individualized dose adjustments in children following organ transplantation. Ganciclovir AUCs were calculated from four plasma drug levels in pediatric SOT recipients aged six months through three yr receiving valganciclovir suspension by mouth. Of the 28 ganciclovir AUC calculations performed, 11 (39%) were outside the therapeutic target range of 40-60 mcg h/L leading to a valganciclovir dose adjustment. Current manufacturer-recommended dosing based on BSA and CrCl was estimated to result in therapeutic AUCs in fewer patients than the simple weight-based formula used in our institution (4 vs. 13; p = 0.017). An AUC calculation using only the two- and five-h measurements was strongly correlated with the AUC using all four time measurements (R(2) = 0.846; p < 0.001). A simple weight-based dosing approach gives a higher probability for therapeutic AUCs compared to the manufacturer-recommended dosing in pediatric transplant patients aged six months through three yr with normal renal function. An AUC calculated using two sample times might allow for fewer blood draws in the future.
authors.affiliation: Department of Pharmacy, Seattle Children's Hospital, Seattle, WA, USA. david.villenueve@seattlechildrens.org
authors.forename: David
authors.initials: D
authors.lastname: Villeneuve
authors.forename: Adam
authors.initials: A
authors.lastname: Brothers
authors.forename: Eric
authors.initials: E
authors.lastname: Harvey
authors.forename: Mariska
authors.initials: M
authors.lastname: Kemna
authors.forename: Yuk
authors.initials: Y
authors.lastname: Law
authors.forename: Thomas
authors.initials: T
authors.lastname: Nemeth
authors.forename: Soren
authors.initials: S
authors.lastname: Gantt
mesh_terms: D000284:Administration, Oral; D000465:Algorithms; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D001835:Body Weight; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000517:prevention & control; D004334:Drug Administration Schedule; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007223:Infant; D016377:Organ Transplantation / Q000379:methods*; D015203:Reproducibility of Results; D016896:Treatment Outcome; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir