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Relations exposition-effets et pharmacogénétique du ganciclovir chez le patient transplanté

Abstract : Cytomegalovirus infection is a major issue in transplant patients as it affects the graft survival and contributes to patients’ morbi-mortality. The implementation of ganciclovir prophylaxis has significantly decreased its incidence, however GCV frequently induces neutropenia. This adverse effect leads to a decrease in the ganciclovir dose or to a discontinuation of the therapy, thereby favoring viral resistance. Resistance to ganciclovir is a growing problem in solid organ transplantion because of the lack of proper data to support treatment decisions when it is encountered. In this context we aim at better understanding the factors involved in this toxicity. First we explored the intracellular metabolism of ganciclovir in patients’ white blood cells. We found that the active form of ganciclovir is associated with neutrophil toxicity at month 3 of treatment. Then we explored the effect of targeted polymorphisms among transporter genes in two cohorts of renal transplant patients. We found that a single nucleotide polymorphism is strongly associated with a decrease in the neutrophil count and in ganciclovir intracellular accumulation. This thesis provides relevant tools for a deeper exploration of ganciclovir intracellular metabolism and accumulation which might be useful for the prevention of ganciclovir induced neutropenia.
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Submitted on : Friday, October 30, 2015 - 1:32:08 PM
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  • HAL Id : tel-01222712, version 1



Pierre-André Billat. Relations exposition-effets et pharmacogénétique du ganciclovir chez le patient transplanté. Médecine humaine et pathologie. Université de Limoges, 2015. Français. ⟨NNT : 2015LIMO0050⟩. ⟨tel-01222712⟩



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