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

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. 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 (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.