title: Pharmacokinetics of ganciclovir during continuous venovenous hemodiafiltration in critically ill patients.
abstract: Ganciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.
authors.affiliation: Department of Internal Medicine 3, Intensive Care Unit 13H1, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Horvatits
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kitzberger
authors.forename: Andreas
authors.initials: A
authors.lastname: Drolz
authors.forename: Christian
authors.initials: C
authors.lastname: Zauner
authors.forename: Walter
authors.initials: W
authors.lastname: Jäger
authors.forename: Michaela
authors.initials: M
authors.lastname: Böhmdorfer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kraff
authors.forename: Achim
authors.initials: A
authors.lastname: Fritsch
authors.forename: Florian
authors.initials: F
authors.lastname: Thalhammer
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuhrmann
authors.forename: Peter
authors.initials: P
authors.lastname: Schenk
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000097:blood* / Q000493:pharmacokinetics*; D016638:Critical Illness; D005260:Female; D015774:Ganciclovir / Q000097:blood* / Q000493:pharmacokinetics*; D017583:Hemodiafiltration; D006801:Humans; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir