Prophylactic oral ganciclovir after renal transplantation-dosing and pharmacokinetics

Abstract.

Ganciclovir alone or in combination with hyperimmunoglobulin is replacing other treatment modalities for the prophylactic treatment of cytomegalovirus (CMV) infections. No dose recommendations are available for oral ganciclovir therapy in children with impaired renal function after renal transplantation of a kidney from a CMV IgG-positive donor. We undertook a pharmacokinetic study in 14 pediatric renal transplant recipients who were CMV IgG negative and had received a graft from a CMV IgG-positive donor. We estimated the daily dosage of oral ganciclovir in relation to the glomerular filtration rate (GFR). Oral ganciclovir was administered at a starting dose of 3 × 1 g for children with a weight above 50 kg, 3 × 750 mg for children between 50 and 37.5 kg, and 3 × 500 mg for children between 37.5 and 24 kg. The starting dose was reduced by 50% for GFR values ≤50 ml/min per 1.73 m² and by 75% for GFR values ≤25 ml/min per 1.73 m². The daily dose was divided into three daily doses unless GFR was <40 ml/min per 1.73 m², when only two daily doses were given. Doses were adjusted according to the measured plasma trough concentrations (c) using the simple formula: c _ganciclovir(measured)/c _ganciclovir(desired) = dosage rate(used)/dosage rate(adjusted). Mean stable plasma trough concentration was 0.91±0.68 μg/ml. The dosage rate, adjusted to a trough concentration of 1.0 μg/ml, correlated with the GFR. The dose per day could be calculated according to a simple equation for a GFR <100 ml/min per 1.73 m²: dosage per day (mg/kg per day) = GFR. No CMV disease developed in any of the patients during oral ganciclovir, but 1 patient developed an acute rejection episode and a positive pp65 antigen 5 weeks after discontinuation of ganciclovir. The drug was well tolerated and without side effects.