Ganciclovir (BW 759) hydrate is a nucleoside analogue that is an orally active antiviral agent with anti-cytomegalovirus activity. Ganciclovir hydrate is also active against members of the herpes group and some other DNA viruses in vitro. Ganciclovir hydrate inhibits the replication of human herpes viruses (HSV 1 and 2, CMV) and adenovirus serotypes 1, 2, 4, 6, 8, 10, 19, 22 and 28 in vitro. Ganciclovir hydrate also has an IC 50 of 5.2 μM against feline herpesvirus type-1 ( FHV-1 ) and can diffuse into the brain [1] [2] [3].

Ganciclovir (BW 759) 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 μM versus 72 μM for acyclovir [4]. 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 [5].

Ganciclovir (BW 759) (50 mg/kg; i.p.; twice a day for five injections) significantly decreases white blood cells, red blood cells and platelets in newborn mice, and can diffuse into the brain and the perilymphatic space of the inner ear [3]. Ganciclovir (1-80 mg/kg; i.h.; daily for 5 days) delays murine cytomegalovirus (MCMV)-induced wasting syndrome and mortality [6]. Animal Model: Non-inbred Oncins France 1 (OF1) mice and albino rats non-immunized for MCMV [3] Dosage: 50 mg/kg Administration: Intraperitoneal injection, twice a day for five injections (mice) or 3 days (adult rats) (Pharmacokinetic Study) Result: In adult rats, the intracochlear diffusion of Ganciclovir was shown to achieve the same concentration as in blood. In gestating mice, transplacental diffusion was observed, with a fetal-to-maternal blood ratio of 0.5. In newborn mice, the plasma concentration profile of Ganciclovir showed a peak at 2 h followed by a gradual decrease. In adult mice, the concentration peaked at 1 h, but became undetectable by 2 h after injection. Significantly decreased white blood cells, red blood cells and platelets in newborn mice. Animal Model: Female SCID mice inoculated with MCMV [6] Dosage: 0, 1, 10, 80 and 160 mg/kg Administration: Subcutaneous injection, once daily for 5 days Result: Dose dependently delayed the wasting syndrome and mortality in a dose range up to 80 mg/kg per day, whereas a dose of 160 mg/kg per day induced reversible side-effects.