Ganciclovir exposure under a 450 mg daily dosage of valganciclovir for cytomegalovirus prevention in kidney transplantation: a prospective study

• Published in: Clinical transplantation Vol. 24; no. 6; pp. 794 - 800
• Main Authors: Manuel, Oriol, Pascual, Manuel, Perrottet, Nancy, Lamoth, Frédéric, Venetz, Jean-P., Decosterd, Laurent A., Buclin, Thierry, Meylan, Pascal R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2010; Wiley
• Subjects: Adult; Aged; Antiviral Agents - administration & dosage; antiviral prophylaxis; Biological and medical sciences; creatinine clearance; Cytomegalovirus - drug effects; Cytomegalovirus Infections - prevention & control; Cytomegalovirus Infections - virology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Ganciclovir - administration & dosage; Ganciclovir - analogs & derivatives; Glomerular Filtration Rate; Humans; Infectious diseases; Kidney Transplantation; Male; Medical sciences; Middle Aged; organ transplantation; Pharmacokinetics; Prospective Studies; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Survival Rate; Tissue Distribution; Tissue, organ and graft immunology; Viral diseases; Acyclic nucleoside; Purine nucleoside; Clearance; Homotransplantation; Betaherpesvirinae; Posology; Kidney; Human cytomegalovirus; Prospective; Prevention; Ganciclovir; organ transplantation; Surgery; Nucleoside analog; Antiviral; Graft; antiviral prophylaxis; DNA polymerase inhibitor; Creatinine; Opportunistic infection; Valganciclovir; Herpesviridae; Exposure; Prodrug; creatinine clearance; Infection; Virus; Medicine; Treatment; Urinary system; Viral disease; Pharmacokinetics; Organ; Kidney transplantation
• ISSN: 0902-0063; 1399-0012
• DOI: 10.1111/j.1399-0012.2009.01205.x

Manuel O, Pascual M, Perrottet N, Lamoth F, Venetz J‐P, Decosterd LA, Buclin T, Meylan PR. Ganciclovir exposure under a 450 mg daily dosage of valganciclovir for cytomegalovirus prevention in kidney transplantation: a prospective study. 
Clin Transplant 2010: 24: 794–800. © 2010 John Wiley & Sons A/S. :  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 (Ctrough) 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 Ctrough 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 GFRMDRD 26–39 mL/min, 35.8 mg h/L (24.9–55.8) in patients with GFRMDRD 40–59 mL/min, and 29.6 mg h/L (22.0–43.2) in patients with GFRMDRD ≥ 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.