title: Ganciclovir pharmacokinetic parameters do not change when extending valganciclovir cytomegalovirus prophylaxis from 100 to 200 days.
abstract: BACKGROUND
  A 3-month course of prophylaxis is usually recommended for cytomegalovirus (CMV) D+/R- renal transplant recipients. Based on recent data, up to 6 months of prophylaxis may be used. A subanalysis was performed to evaluate the pharmacokinetics of ganciclovir after valganciclovir administration and to perform an exploratory pharmacokinetic/pharmacodynamic analysis.
  
  
  METHODS
  In Improved Protection Against Cytomegalovirus in Transplant, a phase III, randomized, double blind, placebo-controlled, multicenter study, 318 CMV D+/R- kidney transplant recipients received valganciclovir prophylaxis (900 mg once daily) for 200 or 100 days. A population pharmacokinetic analysis was conducted on a subgroup of patients (n=120). The relationships between ganciclovir exposure (AUC0-24 hr) and clinical outcomes were explored.
  
  
  RESULTS
  The final population parameter estimates (95% confidence interval) were as follows: apparent clearance of ganciclovir, 12 L/hr (11.3-12.7 L/hr); volume of distribution, 18.5 L (14.4-22.6 L); and peripheral volume, 44.4 L (40.2-48.6 L). No differences were apparent between the two treatment groups and these estimates. These results are consistent with previously published pharmacokinetic models. There were no direct correlations between the likelihood of developing hematologic adverse events and ganciclovir exposure at the time of the event. The incidence of CMV disease was not correlated with ganciclovir exposure.
  
  
  CONCLUSIONS
  The pharmacokinetics of ganciclovir were similar between the two dosing groups (100 vs. 200 days), with the majority of patients achieving an area under the concentration time curve in the target therapeutic range (40-60 μg hr/mL). The fact that the majority of patients were within the target therapeutic range and the absence of a control arm (no treatment) precluded any attempt to validate a correlation with clinical parameters (i.e., CMV disease).
authors.affiliation: F. Hoffmann-La Roche AG, Basel, Switzerland. horst.welker@roche.com
authors.forename: Horst
authors.initials: H
authors.lastname: Welker
authors.forename: Mahdi
authors.initials: M
authors.lastname: Farhan
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
authors.forename: Carla
authors.initials: C
authors.lastname: Washington
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D003404:Creatinine / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000517:prevention & control*; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology; D011336:Probability; D013997:Time Factors; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D003404:Creatinine; D000077562:Valganciclovir; D015774:Ganciclovir