These kinases are present in 10-fold greater concentrations in CMV or herpes simplex virus (HSV)-infected cells compared to uninfected human cells, allowing ganciclovir triphosphate to concentrate in infected cells.Ganciclovir triphosphate is a competitive inhibitor of deoxyguanosine triphosphate (dGTP). It is incorporated into viral DNA and preferentially inhibits viral DNA polymerases more than cellular DNA polymerases. Ganciclovir triphosphate serves as a poor substrate for chain elongation. Once incorporated into viral DNA due to its structure similarity to dGTP, chain termination occurs once a single nucleotide is added to the distal hydroxyl group of the incomplete deoxyribose ring of ganciclovir. Pharmacokinetics
Oral bioavailability is approximately 60%. Fatty foods significantly increase the bioavailability and the peak level in the serum. It takes about 2 hours to reach maximum concentrations in the serum. Valganciclovir is eliminated as ganciclovir in the urine, with a half-life of about 4 hours in people with normal kidney function. The mechanism of this drug is activation via a viral protein kinase HCMV UL97 and subsequent phosphorylation by cellular kinases. The phosphotransferase enzyme can likewise activate valganciclovir. Chemistry
The synthesis of valganciclovir has been reviewed. Many routes use ganciclovir as a starting material. Society and culture
Price and patent status
Roches Valcyte is protected by patent. However a generic version manufactured by Japanese-owned Indian company Daiichi-Ranbaxy was found by the District Court of New Jersey, USA not to infringe Roches patent. In November 2014, FDA approved generics by two manufacturers.The price of a four-month course of valganciclovir from Roche is about US$8,500 in high-income countries, $6,000 in India.
Valganciclovir, sold under the brand name Valcyte among others, is an antiviral medication used to treat cytomegalovirus (CMV) infection in those with HIV/AIDS or following organ transplant. It is often used long term as it only suppresses rather than cures the infection. Valganciclovir is taken by mouth.Common side effects include abdominal pain, headaches, trouble sleeping, nausea, fever, and low blood cell counts. Other side effects may include infertility and kidney problems. When used during pregnancy, it causes birth defects in some animals. Valganciclovir is the L-valyl ester of ganciclovir and works when broken down into ganciclovir by the intestine and liver.Valganciclovir was approved for medical use in 2001. It is on the World Health Organizations List of Essential Medicines. In 2017, a generic version was approved. Medical uses
Adults
Valganciclovir is commonly used for treatment of cytomegalovirus (CMV) retinitis (eye infection may cause blindness) in people who have acquired immunodeficiency syndrome (AIDS). Valganciclovir is also used to prevent cytomegalovirus disease in people who have received a heart, kidney, or kidney-pancreas transplant and who have a chance of getting CMV disease. Overall, valganciclovir works by preventing the spread of CMV disease or slowing the growth of CMV. Children
Valganciclovir is used for the prevention of CMV disease in people following kidney transplant (4 months to 16 years of age) and heart transplant (1 month to 16 years of age) at high risk. Side effects
Valganciclovir is commonly associated with vomiting, abdominal pain, diarrhea, and headache.