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Valganciclovir - Brands
Valganciclovir is an L-valyl ester (prodrug) of ganciclovir, which after oral administration is rapidly converted to ganciclovir by intestinal and hepatic esterases. Ganciclovir is a synthetic analogue of 2’-deoxyguanosine, which inhibits replication of herpes viruses in vitro and in vivo. Sensitive human viruses include human cytomegalovirus (HCMV), herpes simplex virus-1 and -2 (HSV-1 and HSV-2), human herpes virus 6, 7 and 8 (HHV-6, HHV-7, HHV-8), Epstein-Barr virus (EBV), varicella-zoster virus (VZV) and hepatitis B virus.
In CMV-infected cells ganciclovir is initially phosphorylated to ganciclovir mono-phosphate by the viral protein kinase, UL97. Further phosphorylation occurs by cellular kinases to produce ganciclovir triphosphate, which is then slowly metabolized intracellularly. This has been shown to occur in HSV- and HCMV-infected cells with half-lives of 18 and between 6 and 24 hours respectively after removal of extracellular ganciclovir. As phosphorylation is largely dependent on the viral kinase, the phosphorylation of ganciclovir occurs preferentially in virus-infected cells.
The virustatic activity of ganciclovir is due to inhibition of viral DNA synthesis by: (a) competitive inhibition of incorporation of deoxyguanosine-triphosphate into DNA by viral DNA polymerase and (b) incorporation of ganciclovir triphosphate into viral DNA causing termination of, or very limited further viral DNA elongation. Typical antiviral IC 50 against CMV in vitro is in the range 0.08 μM (0.02 μg/ml) to 14 μM (3.5 μg/ml).
The clinical antiviral effect of Valganciclovir has been demonstrated in the treatment of AIDS patients with newly diagnosed CMV retinitis (clinical trial WV15376). CMV shedding was decreased from 46% (32/69) of patients at study entry to 7% (4/55) of patients following 4 weeks of Valganciclovir treatment.
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