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 has been paritally analyzed and presented as an abstract and oral presentation at the World Transplant Congress in July 2006. Intravenous ganciclovir (GCV) and oral valganciclovir (vGCV) 900mg daily provided similar drug exposures. Oral vGCV 450mg trended toward greater drug exposure than oral GCV 1G TID, with vGCV providing higher area under the curve in all but one patient. No patient experienced CMV viremia during the study period and the most common adverse effects were leucopenia and anemia. Oral vGCV 900mg daily provided systemic GCV exposure similar, to IV GCV, indicating that vGCV is well-absorbed in the early period following kidney transplantation. Other data analysis is being conducted comparing minimum concentrations of ganciclovir between dosage forms and comparing PK parameters between valganciclovir 900mg and 450mg doses (further characterize pharmacokinetic parameters). A manuscript is currently being prepared for journal submission in the Fall of 2006. 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|