title: Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation.
abstract: Cytomegalovirus (CMV) infection is a major complication after allogeneic stem cell transplantation (SCT). Valganciclovir (V-GCV) is an oral prodrug hydrolyzed to the anti-CMV drug ganciclovir (GCV). A randomized, multicenter, crossover, open-label clinical trial compared exposure to GCV after V-GCV and intravenous GCV (IV-GCV) as preemptive therapy for CMV disease in SCT. The primary objective was to compare exposure to GCV in patients with CMV infection stratified for intestinal graft-versus-host disease (I-GVHD). Secondary objectives were the assessment of safety and efficacy. Patients without I-GVHD had a higher exposure to GCV after V-GCV when compared with IV-GCV (area under the concentration-time curve from drug administration to last observed concentration after 12 hours [AUC(0-12)] 53.8 +/- 17.97 microg/mL . h [mean +/- SD] vs 39.5 +/- 13.91; P < .001; ratio of V-GCV/IV-GCV was 1.4; 90% confidence interval [CI], 1.2-1.5). This was also true in patients with I-GVHD grades I-II (AUC(0-12) 52.9 +/- 21.75 vs 33.1 +/- 12.97 mug/mL . h; P = .018; ratio 1.6; 90% CI, 1.3-2.0). Absolute bioavailability of GCV after V-GCV was approximately 75% in individuals with or without I-GVHD grades I-II. No severe GCV-related toxicity was observed and efficacy and safety was comparable (84-day follow-up). This supports the use of V-GCV in SCT, even in patients with I-GVHD grades I-II. Due to higher exposure after V-GCV compared with IV-GCV, patients should be monitored carefully for safety reasons.
authors.affiliation: University of Würzburg, Department of Internal Medicine II, Klinikstr. 6-8, 97070 Würzburg, Germany. einsele_h@klinik.uni-wuerzburg.de
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Pierre
authors.initials: P
authors.lastname: Reusser
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Peter
authors.initials: P
authors.lastname: Kalhs
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Holger
authors.initials: H
authors.lastname: Hebart
authors.forename: Yves
authors.initials: Y
authors.lastname: Chalandon
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Bernd
authors.initials: B
authors.lastname: Hertenstein
authors.forename: Frank
authors.initials: F
authors.lastname: Rohde
mesh_terms: D000284:Administration, Oral; D000328:Adult; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D033581:Stem Cell Transplantation / Q000379:methods*; D014184:Transplantation, Homologous / Q000276:immunology; D000077562:Valganciclovir
chemical_list: D000077562:Valganciclovir; D015774:Ganciclovir