Oral valganciclovir: a new option for treatment of cytomegalovirus infection and disease in immunocompromised hosts
P Reusser
Abstract
P Reusser
Abstract
Immunocompromised hosts are at increased risk of cytomegalovirus (CMV) infection and serious CMV disease. CMV infection is an important cause of morbidity among patients infected with HIV and after solid organ transplantation (SOT) and may cause life-threatening disease in allogeneic stem cell transplant (SCT) recipients. The introduction into clinical use of potent antiviral compounds and of rapid detection assays for CMV during the past two decades has allowed development of strategies for the prevention and treatment of disease caused by CMV in these groups of immunocompromised patients. At present, the antiviral drugs ganciclovir, foscarnet and cidofovir are commonly used in the treatment of CMV infection and disease. However, these agents have a poor oral bioavailability and, for systemic use, require iv. administration for most indications. Valganciclovir is an oral prodrug of ganciclovir, with a 10-fold greater bioavailability than oral ganciclovir. Studies of the pharmacokinetics of valganciclovir among HIV-infected CMV-seropositive patients and liver transplant recipients suggest that this oral compound has the potential to replace both oral and iv. ganciclovir in many situations if it is shown to be as efficacious and safe as those ganciclovir formulations in immunodeficient patients. In the first part of this review, currently established approaches to the management of CMV infection and disease in SCT and SOT recipients and HIV-infected patients are discussed to highlight possible indications for future valganciclovir use; in the second part, data from human studies of valganciclovir are presented.
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Immunocompromised hosts are at increased risk of cytomegalovirus (CMV) infection and serious CMV disease. CMV infection is an important cause of morbidity among patients infected with HIV and after solid organ transplantation (SOT) and may cause life-threatening disease in allogeneic stem cell transplant (SCT) recipients. The introduction into clinical use of potent antiviral compounds and of rapid detection assays for CMV during the past two decades has allowed development of strategies for the prevention and treatment of disease caused by CMV in these groups of immunocompromised patients. At present, the antiviral drugs ganciclovir, foscarnet and cidofovir are commonly used in the treatment of CMV infection and disease. However, these agents have a poor oral bioavailability and, for systemic use, require iv. administration for most indications. Valganciclovir is an oral prodrug of ganciclovir, with a 10-fold greater bioavailability than oral ganciclovir. Studies of the pharmacokinetics of valganciclovir among HIV-infected CMV-seropositive patients and liver transplant recipients suggest that this oral compound has the potential to replace both oral and iv. ganciclovir in many situations if it is shown to be as efficacious and safe as those ganciclovir formulations in immunodeficient patients. In the first part of this review, currently established approaches to the management of CMV infection and disease in SCT and SOT recipients and HIV-infected patients are discussed to highlight possible indications for future valganciclovir use; in the second part, data from human studies of valganciclovir are presented.
Key concepts: Valganciclovir, Ganciclovir, Cidofovir, Foscarnet, Cytomegalovirus, Medicine, Transplantation, Immunology