title: Pharmacokinetics of oral valganciclovir solution and intravenous ganciclovir in pediatric renal and liver transplant recipients.
abstract: In an open-label, prospective, pharmacokinetic assessment, we evaluated total drug exposure (area under the curve [AUC]) of intravenous (IV) ganciclovir (GCV) and oral (p.o.) valganciclovir when normalized for body surface area (BSA) in pediatric liver (n=20) and renal (n=26) transplant patients Reference doses for IV GCV (200 mg/m(2)) and p.o. valganciclovir (520 mg/m(2)) were based on adult doses, and adjusted for BSA initially, and BSA and renal function (estimated via creatinine clearance [CrCL]) thereafter. Renal transplant patients received GCV on days 1-2, valganciclovir 260 mg/m(2) on day 3, and valganciclovir 520 mg/m(2) on day 4. Liver transplant patients received twice daily GCV from enrollment to day 12, and then valganciclovir twice daily on days 13-14. GCV pharmacokinetics were described using a population pharmacokinetic approach. Type of solid organ transplant (kidney or liver) had no effect on GCV pharmacokinetics. Median GCV exposure following valganciclovir 520 mg/m(2) was similar to that with IV GCV, and to that reported in adults. Patients <5 years of age had AUC values approximately 50% of those compared with older age ranges; dosing based on both BSA and CrCL increased drug exposure in younger patients. A dosing algorithm based on BSA and CrCL should be tested in future studies.
authors.affiliation: Department of Surgery, Indiana University, Indianapolis, Indiana 46202-5124, USA. mpescov@iupui.edu
authors.forename: M D
authors.initials: MD
authors.lastname: Pescovitz
authors.forename: R B
authors.initials: RB
authors.lastname: Ettenger
authors.forename: C F
authors.initials: CF
authors.lastname: Strife
authors.forename: J R
authors.initials: JR
authors.lastname: Sherbotie
authors.forename: S E
authors.initials: SE
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: McDiarmid
authors.forename: S
authors.initials: S
authors.lastname: Bartosh
authors.forename: J
authors.initials: J
authors.lastname: Ives
authors.forename: M R
authors.initials: MR
authors.lastname: Bouw
authors.forename: J
authors.initials: J
authors.lastname: Bucuvalas
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001830:Body Surface Area; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D016030:Kidney Transplantation / Q000009:adverse effects*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D000077562:Valganciclovir; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D003404:Creatinine; D000077562:Valganciclovir; D015774:Ganciclovir