ORAL GANCICLOVIR DOSING IN TRANSPLANT RECIPIENTS AND DIALYSIS PATIENTS BASED ON RENAL FUNCTION1

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Abstract
An oral formulation of ganciclovir (GCV) was recently approved for the prevention of cytomegalovirus disease in solid organ transplant recipients. This study was designed to determine the bioavailability of GCV and to test a dosing algorithm in transplant and dialysis patients with different levels of renal function. Pharmacokinetic studies were carried out in 23 patients who were either a recipient of an organ transplant or on hemodialysis. Drug dosing was established by the following algorithm based on calculated creatinine clearance (CrCl): Equation 1 that is, CrCl >50 ml/min, 1000 mg every 8 hr; CrCl of 25-50 ml/min, 1000 mg every 24 hr; CrCl of 10-24 ml/min, 500 mg every day; CrCl The following GCV concentrations (mean ± SD) were determined: with CrCl of ≥70 ml/min, the minimum steady-state concentration (Cmin) and maximum concentration (Cmax) were 0.78±0.46 µg/ml and 1.42±0.37 µg/ml, respectively, with a 24-hr area under the concentration time curve (AUC0-24) of 24.7±7.8 µg·hr/ml; with CrCl of 50-69 ml/min, the Cmin and Cmax were 1.93±0.48 and 2.57±0.39 µg/ml, respectively, with an AUC0-24 of 52.1±10.1 µg·hr/ml; with CrCl of 25-50 ml/min, the Cmin and Cmax were 0.41±0.27 and 1.17±0.32 µg/ml, respectively, with an AUC0-24 of 14.6±7.4 µg·hr/ml. For one patient with a CrCl of 23.8 ml/min, the Cmin and Cmax were 0.32 and 0.7 µg/ml, respectively, with an AUC0-24 of 10.7 µg·hr/ml. With CrCl of min The bioavailability of oral GCV in transplant patients was similar to that observed in human immunodeficiency virus-infected patients. However, levels between 0.5 and 1 µg/ml (within the IC50 of most cytomegalovirus isolates) could be achieved with tolerable oral doses. The proposed dosing algorithm resulted in adequate levels for patients with CrCl greater than 50 ml/min and for patients on dialysis. For patients with CrCl between 10 and 50 ml/min, the levels achieved were low and these patients would likely benefit from increased doses.