Ganciclovir and valganciclovir: An overview
- Kimon C Zachary, MD
Kimon C Zachary, MD
- Assistant Professor of Medicine
- Harvard Medical School
Ganciclovir was the first antiviral agent approved for the treatment of cytomegalovirus (CMV) infection. It is widely used for the treatment of CMV infections among patients with impaired cell-mediated immunity, particularly persons with poorly controlled and advanced HIV/AIDS, and recipients of solid organ and bone marrow transplantation, who are at high risk for invasive CMV disease. Valganciclovir, an oral prodrug that is rapidly converted to ganciclovir, also plays a major role in the treatment and prevention of CMV infections in immunocompromised hosts.
An overview of the basic pharmacology, pharmacokinetics, and toxicities of ganciclovir and valganciclovir will be discussed here. Treatment of specific clinical syndromes can be found in the appropriate topics. (See "Treatment of AIDS-related cytomegalovirus retinitis" and "AIDS-related cytomegalovirus gastrointestinal disease" and "Cytomegalovirus infection as a cause of pulmonary disease in HIV-infected patients" and "Clinical manifestations, diagnosis, and management of cytomegalovirus disease in kidney transplant recipients" and "Prevention of cytomegalovirus infection in lung transplant recipients" and "Pulmonary complications after allogeneic hematopoietic cell transplantation".)
MECHANISM OF ACTION
Ganciclovir (9-[(1,3,-dihydroxy-2-propoxy)methyl] guanine, or DHPG) is an acyclic analog of the nucleoside guanosine. The drug is converted intracellularly to ganciclovir 5'-monophosphate by a viral kinase, which is encoded by the cytomegalovirus (CMV) gene UL97 during infection. Subsequently, cellular kinases catalyze the formation of ganciclovir diphosphate and ganciclovir triphosphate, which is present in 10-fold greater concentrations in CMV or herpes simplex virus (HSV)-infected cells than uninfected cells.
Ganciclovir triphosphate is a competitive inhibitor of deoxyguanosine triphosphate incorporation into DNA and preferentially inhibits viral DNA polymerases more than cellular DNA polymerases. In addition, ganciclovir triphosphate serves as a poor substrate for chain elongation, thereby disrupting viral DNA synthesis by a second route [1-3].
SPECTRUM OF ACTIVITY
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