This study will compare different ways of giving the drugs ganciclovir and valganciclovir to kidney or kidney and pancreas transplant recipients to determine if valganciclovir is providing similar protection against cytomegalovirus (CMV) compared with conventional therapy with ganciclovir. The reason for this comparison is that valganciclovir is better absorbed and has the advantage of once a day oral dosing. The pharmacokinetics of this drug has been studied in patients with HIV infection and CMV infection and during September 2003 received FDA approval for prophylaxis of CMV infection in high risk patients undergoing kidney, heart and kidney-pancreas transplantation at a dose of 900mg per day. This study will further review the pharmcokinetics of valganciclovir in kidney transplant recipients and focus on using a lower dose of valganciclovir to reduce toxicity. CMV is a serious viral infection occurring following organ transplant that can result in significant illness or death. Seven males and 4 females were enrolled and enrollment is now complete. This study consists of four phases. Each phase or drug dose has been selected to mimic ganciclovir and valganciclovir use in the kidney transplant population. The first phase consists of serial blood sampling for ganciclovir blood levels after intravenous ganciclovir. The second phase consists of serial blood sampling for ganciclovir levels following oral valganciclovir at 900mg per day. These two phases will be compared for equivalency of drug levels and exposure. The third phase consists of serial blood levels following 450 mg of oral valganclovir daily. The fourth phase consists of serial blood samples after oral ganciclovir 1 gram every 8 hours. The third and fourth phases will be compared for equivalency of drug levels and exposure. At this time, all seven subjects each for the phase I and II comparison and the phase III and IV comparison have completed blood level sampling. Drug levels have been assayed and the data is currently being analyzed. Preliminary findings show that the mean area under the curve (AUC, total drug exposure) of oral valganciclovir was similar to the ganciclovir intravenous dose of 2.5mg/kg every 12 hours and the mean AUC (total drug exposure) of oral valganciclovir 450mg dose was similar to oral ganciclovir 1000mg three times daily. Levels will also be compared to estimated renal function and weight. Final analysis is expected to be completed by November 2005. By characterizing the pharmacokinetics of valganciclovir in the kidney transplant population, it is hoped that appropriate dosing to prevent CMV disease and limit toxicity may be achieved. This research will also be useful as a foundation to study the pharmacokinetics of valganciclovir in organ transplant patients with compromised renal function.
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|Chamberlain, Christine E; Fitzgibbon, Edmond; Wassermann, Eric M et al. (2005) Idiopathic intracranial hypertension following kidney transplantation: a case report and review of the literature. Pediatr Transplant 9:545-50|
|Kirk, Allan D; Mannon, Roslyn B; Kleiner, David E et al. (2005) Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin. Transplantation 80:1051-9|