title: Pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir in allogeneic stem cell transplant patients with graft-versus-host disease of the gastrointestinal tract.
abstract: The pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir were compared in allogeneic stem cell transplant recipients with stable graft-versus-host disease of the gastrointestinal tract. Twenty-two evaluable adult patients were randomized to receive a single dose of open-label study drug (900 mg of oral valganciclovir or 5 mg/kg of intravenous ganciclovir). After a washout period of 2 to 7 days, patients were crossed over to receive the alternate study drug. Ganciclovir and valganciclovir concentrations in plasma were measured over 24 hours after dosing. Noninferiority of 900 mg of valganciclovir relative to intravenous ganciclovir was concluded if the lower limit of the 1-sided 95% confidence interval of the ratio of least-square means of the ganciclovir area under the curve (AUC) for the 2 study drugs was >80%. Valganciclovir was found to be rapidly absorbed and converted into ganciclovir. The ganciclovir exposure after 900 mg of valganciclovir noninferior to that of intravenous ganciclovir (AUC0-infinity, 52.1 and 53.8 microg.h/mL, respectively; 95% confidence interval of the ratio of least square means of AUC0-infinity, 82.48%-118.02%). Oral valganciclovir could be a useful alternative to intravenous ganciclovir in certain stable stem cell transplant patients who require prophylaxis or preemptive therapy for cytomegalovirus infection.
authors.affiliation: Department of Medicine, University of California-Los Angeles Medical Center, Los Angeles, California 90095, and Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA, USA. dwinston@mednet.ucla.edu
authors.forename: Drew J
authors.initials: DJ
authors.lastname: Winston
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Don A
authors.initials: DA
authors.lastname: Gabriel
authors.forename: Christos
authors.initials: C
authors.lastname: Emmanouilides
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: W Robert
authors.initials: WR
authors.lastname: Lange
authors.forename: Voravit
authors.initials: V
authors.lastname: Ratanatharathorn
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir