tcsc2014 Ganciclovir

Ganciclovir is a potent inhibitor of viruses of the herpes family, including cytomegalovirus (CMV), with an IC₅₀ of 5.2 μM for feline herpesvirus type-1 (FHV-1).

IC50 & Target: IC50: 5.2 μM (FHV-1)^[1]

In Vitro: Ganciclovir is an acyclic deoxyguanosine analog structurally similar to acyclovir but with superior activity against CMV. The median ganciclovir concentration required to inhibit viral replication by 50 percent is 2.15 mumol versus 72 mumol for acyclovir^[2].The primary mechanism of ganciclovir action against CMV is inhibition of the replication of viral DNA by ganciclovir-5'-triphosphate (ganciclovir-TP). This inhibition includes a selective and potent inhibition of the viral DNA polymerase.Ganciclovir is metabolized to the triphosphate form by primarily three cellular enzymes: a deoxyguanosine kinase induced by CMV-infected cells; guanylate kinase; and phosphoglycerate kinase^[3].

In Vivo: In adult rats, the intracochlear diffusion of ganciclovir is shown to achieve the same concentration as in blood. In gestating mice, transplacental diffusion is observed, with a fetal-to-maternal blood ratio of 0.5. In newborn mice, the plasma concentration profile of ganciclovir shows a peak at 2 h followed by a gradual decrease. In adult mice, the concentration peaked at 1 h, but becomes undetectable by 2 h after injection. Counts of white blood cells, red blood cells and platelets decreases significantly in ganciclovir-treated newborn mice^[4].