Description
Valganciclovir hydrochloride, a prodrug of the antiviral ganciclovir, was launched in the
US for the oral treatment of cytemegalovirus (CMV) retinitis, a sight-threatening
complication in patients with AIDS. This L-Valyl ester prodrug can be prepared in three
steps from the nucleoside analog ganciclovir by trimethylsilyl-protection of the amino
group, coupling with N-benzyloxycarbonyl-L-valine-N-carboxyanhydride, hydrolysis with
hydrochloric acid and hydrogenolysis of the Cbz-protecting group. Valganciclovir is well
absorbed and rapidly hydrolyzed to ganciclovir by intracellular esterases in the intestinal
mucosal cells and by hepatic esterases. Unlike ganciclovir, valganciclovir was
demonstrated to be actively transported by the intestinal peptide transporter PEPT1 in
Caco-2 cells. As a consequence, its absolute bioavailability in human was 10-fold higher
compared to ganciclovir (6%). In clinical trials, it was shown that a twice-daily 900 mg dose
of valganciclovir resulted in similar systemic ganciclovir exposure to 5 mg/kg twice-daily
intravenous injection of ganciclovir. Valganciclovir concentrations could not be quantified in
most patients within three to four hours. In a randomized non-blind phase III clinical trial,
oral valganciclovir (900 mg twice daily for three weeks then 900 mg once daily for one
week) was as effective as intravenous ganciclovir (5 mg/kg twice daily for three weeks
then 5 mg/kg once daily). Oral treatment with valganciclovir avoided catheter-related
infection that sometimes occurred with intravenous ganciclovir.
Chemical Properties
White Crystalline Solid
Originator
Roche (Switzerland)
Uses
Valganciclovir is the valyl ester prodrug of ganciclovir , an antiviral agent used for the treatment of HIV associated retinitis and for the prevention of post transplant cytomegalovirus (CMV) infections. Upon oral administration, intestinal and hepatic esterases rapidly convert valganciclovir to ganciclovir, which can inhibit viral DNA synthesis (IC50 = 0.95 μM) by targeting the CMV polymerase.
Uses
antibacterial, inhibits protein synthesis
Uses
Valganciclovir hydrochloride hydrate may be used in HIV-related cell signaling studies.
Uses
A pro-drug of ganciclovir. Used in treatment of retro-virus
brand name
Valcyte (Roche).
General Description
Valganciclovir Hydrochloride is the L-valyl ester of ganciclovir and an antiviral drug, widely used to treat cytomegalovirus infections.
Certified pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to pharmacopeia primary standards.
Biochem/physiol Actions
Valganciclovir hydrochloride hydrate is an antiviral used to treat cytomegalovirus infection. It is the prodrug of ganciclovir, a synthetic analog of 2′-deoxy-guanosine which is phosphorylated to a dGTP analog that competitively inhibits the incorporation of dGTP by viral DNA polymerase.
Side effects
Side effects of Valganciclovir hydrochloride include: leukopenia, neutropenia, anaemia, thrombocytopenia, pancytopenia, bone marrow failure and aplastic anaemia. Based on animal data and limited human data, Valganciclovir Oral Solution may temporarily or permanently inhibit spermatogenesis in males and inhibit fertility in females, which in turn may lead to birth defects in humans. It may also cause cancer in humans.
