title: Population pharmacokinetics of valganciclovir prophylaxis in paediatric and adult solid organ transplant recipients.
abstract: OBJECTIVE
  Our aims were to quantify ganciclovir pharmacokinetics in paediatric and adult kidney, liver and lung transplant patients taking a range of valganciclovir doses to prevent herpes virus infections, including a 450 mg regimen, and to identify sources of pharmacokinetic variability.
  
  
  METHODS
  Plasma samples were collected at 2, 4, 8 and 12 weeks post-transplant and at 4, 6, 8 and 12 months post-transplant in subjects prescribed longer courses. Ganciclovir was measured by liquid chromatography/ultraviolet detection. Non-linear mixed effects modelling was used to analyze the concentration-time data and evaluate demographic and transplant-related covariates.
  
  
  RESULTS
  A two compartment model with first order absorption best described the data. Given the range of body sizes, clearance and volume of distribution terms were scaled using standard weight-based allometric exponents. Creatinine clearance was included on apparent oral clearance. Final estimates in a standard 70 kg individual for apparent oral clearance, central volume of distribution, intercompartmental clearance and peripheral volume of distribution were 14.5 l h(-1) , 87.5 l, 4.80 l h(-1) and 42.6 l, respectively. The median terminal half-life for kidney, liver and lung transplant recipients was 9.4, 9.5 and 8.2 h, respectively. Median exposure (i.e. AUC(0,∞) in subjects taking valganciclovir 900 mg or 450 mg once daily was 57.4 and 34.3 μg ml(-1)  h, respectively.
  
  
  CONCLUSIONS
  Allometric scaling allowed simultaneous analysis of data from children and adults. Ganciclovir pharmacokinetics were similar among kidney, liver and lung transplant recipients. Ganciclovir exposure after valganciclovir 450 mg once daily may be suboptimal in some individuals and requires evaluation along with virologic outcomes data.
authors: Department of Experimental and Clinical Pharmacology, University of Minnesota, College of Pharmacy, Minneapolis, Minnesota, United States; Department of Pediatrics, Division of Clinical Pharmacology and Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States.
authors: Heather E
authors: HE
authors: Vezina
authors: Richard C
authors: RC
authors: Brundage
authors: Henry H
authors: HH
authors: Balfour
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D016377:Organ Transplantation; D011446:Prospective Studies; D000077562:Valganciclovir; D014777:Virus Diseases / Q000097:blood / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir
keywords: pharmacokinetics; pharmacometrics; prophylaxis; transplantation; valganciclovir