Indications
Valganciclovir is an antiviral medication primarily indicated for the treatment of cytomegalovirus (CMV) infections. It is specifically utilized in patients who are at significant risk of CMV-related complications, providing a targeted approach to manage and reduce the impact of the virus.
Pharmacodynamics
Valganciclovir functions as a prodrug for ganciclovir, upon which it relies for its antiviral effects against CMV infections. Once administered orally, it undergoes rapid conversion to ganciclovir through the action of intestinal and hepatic esterases. Ganciclovir, being an analogue of guanosine, integrates into viral DNA. This incorporation disrupts the normal activity of DNA polymerase, leading to the termination of viral DNA elongation and thereby inhibiting viral replication.
Absorption
Valganciclovir demonstrates efficient absorption from the gastrointestinal tract. The relative bioavailability of valganciclovir tablets is approximately 60% when administered with food, highlighting the importance of food intake in maximizing the drug's absorption and therapeutic effects.
Metabolism
Following oral administration, valganciclovir undergoes rapid hydrolysis in the intestinal wall and liver to form ganciclovir. This process is efficient and does not result in the creation of any other detectable metabolites, underscoring the specificity of its metabolic pathway.
Mechanism of Action
Valganciclovir acts as a prodrug for ganciclovir, presenting as a blend of two diastereomers. Upon administration, these diastereomers are swiftly converted to ganciclovir by hepatic and intestinal esterases. In cells infected by cytomegalovirus (CMV), ganciclovir undergoes an initial phosphorylation to form ganciclovir monophosphate, facilitated by viral protein kinase. Subsequent phosphorylations by cellular kinases lead to the creation of ganciclovir triphosphate, which is slowly metabolized within the cell. This phosphorylation process is predominantly dependent on viral kinase activity, occurring mainly in virus-infected cells. The antiviral efficacy of ganciclovir stems from the inhibition of viral DNA synthesis through the incorporation of ganciclovir triphosphate into the DNA strand, replacing numerous adenosine bases. This incorporation halts DNA synthesis by preventing the formation of phosphodiester bridges, thereby destabilizing the DNA strand. Notably, ganciclovir exhibits a preferential inhibition of viral DNA polymerases over cellular polymerases, allowing the resumption of DNA chain elongation once ganciclovir is removed.
