title: Ganciclovir exposure under a 450 mg daily dosage of valganciclovir for cytomegalovirus prevention in kidney transplantation: a prospective study.
abstract: This prospective study aimed at determining the ganciclovir exposure observed under a daily dosage of 450 mg valganciclovir routinely applied to kidney transplant recipients with a GFR above 25 mL/min at risk for cytomegalovirus (CMV) disease. Ganciclovir levels at trough (C(trough)) and at peak (C₃(h)) were measured monthly. Ganciclovir exposure (area under the curve [AUC₀₋₂₄]) was estimated using Bayesian non-linear mixed-effect modeling (NONMEM). Thirty-six patients received 450 mg of valganciclovir daily for three months. Median ganciclovir C₃(h) was 3.9 mg/L (range: 1.3-7.1), and C(trough) was 0.4 mg/L (range 0.1-2.7). Median AUC₀₋₂₄ of ganciclovir was 59.3 mg h/L (39.0-85.3) in patients with GFR(MDRD) 26-39 mL/min, 35.8 mg h/L (24.9-55.8) in patients with GFR(MDRD) 40-59 mL/min, and 29.6 mg h/L (22.0-43.2) in patients with GFR(MDRD) ≥ 60 mL/min. No major differences in adverse events according to ganciclovir exposure were observed. CMV viremia was not detected during prophylaxis. After discontinuing prophylaxis, CMV viremia was seen in 8/36 patients (22%), and 4/36 patients (11%) developed CMV disease. Ganciclovir exposure after administration of valganciclovir 450 mg daily in recipients with GFR ≥ 60 mL/min was comparable to those previously reported with oral ganciclovir. A routine daily dose of 450 mg valganciclovir appears to be acceptable for CMV prophylaxis in most kidney transplant recipients.
authors.affiliation: Transplantation Center, University Hospital (CHUV), Lausanne, Switzerland. Oriol.Manuel@chuv.ch
authors.forename: Oriol
authors.initials: O
authors.lastname: Manuel
authors.forename: Manuel
authors.initials: M
authors.lastname: Pascual
authors.forename: Nancy
authors.initials: N
authors.lastname: Perrottet
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lamoth
authors.forename: Jean-P
authors.initials: JP
authors.lastname: Venetz
authors.forename: Laurent A
authors.initials: LA
authors.lastname: Decosterd
authors.forename: Thierry
authors.initials: T
authors.lastname: Buclin
authors.forename: Pascal R
authors.initials: PR
authors.lastname: Meylan
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000517:prevention & control* / Q000821:virology; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005919:Glomerular Filtration Rate; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate; D014018:Tissue Distribution; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir