title: Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients.
abstract: OBJECTIVE
  To determine whether valganciclovir 450 mg every 48 h for cytomegalovirus (CMV) prophylaxis provides appropriate ganciclovir exposure in solid organ transplant recipients during continuous renal replacement therapy (CRRT).
  
  
  METHODS
  Ganciclovir pharmacokinetics was intensively studied in two lung transplant recipients under valganciclovir 450 mg every 48 h over one dosing interval. In vitro experiments using blank whole blood spiked with ganciclovir further investigated exchanges between plasma and erythrocytes.
  
  
  RESULTS
  Ganciclovir disposition was characterized by apparent total body clearance of 3.3 and 5.8 L/h, terminal half-life of 16.9 and 14.1 h, and apparent volume of distribution of 60.3 and 104.9 L in Patients 1 and 2, respectively. The observed sieving coefficient was 1.05 and 0.96, and the haemofiltration clearance was 3.3 and 3.1 L/h. In vitro experiments confirmed rapid efflux of ganciclovir from red blood cells into plasma, increasing the apparent efficacy of haemofiltration.
  
  
  CONCLUSIONS
  A valganciclovir dosage of 450 mg every 48 h appears adequate for patients under CRRT requiring prophylaxis for CMV infection, providing concentration levels in the range reported for 900 mg once daily dosing outside renal failure.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, University Hospital (CHUV), Lausanne, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Perrottet
authors.forename: C
authors.initials: C
authors.lastname: Robatel
authors.forename: P
authors.initials: P
authors.lastname: Meylan
authors.forename: M
authors.initials: M
authors.lastname: Pascual
authors.forename: J P
authors.initials: JP
authors.lastname: Venetz
authors.forename: J D
authors.initials: JD
authors.lastname: Aubert
authors.forename: M M
authors.initials: MM
authors.lastname: Berger
authors.forename: L A
authors.initials: LA
authors.lastname: Decosterd
authors.forename: T
authors.initials: T
authors.lastname: Buclin
mesh_terms: D018890:Chemoprevention / Q000379:methods*; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D017582:Renal Replacement Therapy; D000077562:Valganciclovir
chemical_list: D000077562:Valganciclovir; D015774:Ganciclovir