title: Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients: A Prospective Pharmacokinetic Study.
abstract: Valganciclovir is extensively used for prophylaxis and treatment of cytomegalovirus (CMV) infection in solid-organ transplant recipients. However, pharmacokinetic data in children are scarce, and the pediatric dosing regimen is uncertain. This study sought to prospectively evaluate the pharmacokinetic profile, the clinical efficacy and safety of oral valganciclovir in pediatric transplant recipients and compare different dosing regimens.
  
  
  
  The cohort included solid-organ transplant recipients treated with valganciclovir for CMV prophylaxis in 2014-2015 at a tertiary pediatric medical center. All received a weight-based once-daily oral dose of 17 mg/kg. Ganciclovir concentrations were measured and the area under the curve (AUC0-24) was calculated.
  
  
  
  Thirteen children of median age 7.3 years (interquartile range, 2.2-11.6) were included. Median ganciclovir AUC0-24 was 21.0 mcg·h/mL (interquartile range, 17.1-39.8); 10 patients (77%) attained AUC0-24 <40 mcg·h/mL. Exposure to ganciclovir was about 2-fold lower in young children (<9 years old; P = 0.01) and children with low body surface area (BSA; <0.7 m; P = 0.006) than in their counterparts. Significantly lower doses were recommended with our weight-based protocol than with the manufacturer-recommended BSA- and glomerular filtration rate-based protocol (P = 0.002), reaching a 3-fold difference in infants. No evidence of CMV viremia or disease was observed while prophylaxis was given.
  
  
  
  The weight-based regimen of 17 mg/kg/dose oral valganciclovir results in relatively low ganciclovir exposure, especially in young children with low BSA, yet showed satisfactory clinical efficacy for CMV prophylaxis. The manufacturer's dosing recommendation appears to result in supratherapeutic ganciclovir concentrations. Further studies are needed to establish target AUCs and valganciclovir dosing for CMV prophylaxis in pediatric transplant recipients.
authors.affiliation: From the *Department of Pharmacy, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; †Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; ‡Clinical Pharmacology and Toxicology Unit, Assaf Harofeh Medical Center, Zriffin, Israel; §Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; ¶Department of Epidemiology and Preventive Medicine, School of Public Health, Tel Aviv University, Tel Aviv, Israel; and ‖Biochemistry Laboratory, Assaf Harofeh Medical Center, Zriffin, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Peled
authors.forename: Matitiahu
authors.initials: M
authors.lastname: Berkovitch
authors.forename: Eran
authors.initials: E
authors.lastname: Rom
authors.forename: Efraim
authors.initials: E
authors.lastname: Bilavsky
authors.forename: Yael
authors.initials: Y
authors.lastname: Bernfeld
authors.forename: Lev
authors.initials: L
authors.lastname: Dorfman
authors.forename: Adi
authors.initials: A
authors.lastname: Pappo
authors.forename: Tomer
authors.initials: T
authors.lastname: Ziv-Baran
authors.forename: Nurit
authors.initials: N
authors.lastname: Brandriss
authors.forename: Adina
authors.initials: A
authors.lastname: Bar-Haim
authors.forename: Jacob
authors.initials: J
authors.lastname: Amir
authors.forename: Liat
authors.initials: L
authors.lastname: Ashkenazi-Hoffnung
mesh_terms: D019072:Antibiotic Prophylaxis; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000517:prevention & control*; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D016377:Organ Transplantation; D011183:Postoperative Complications / Q000188:drug therapy / Q000517:prevention & control*; D011446:Prospective Studies; D066027:Transplant Recipients; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir