Sofosbuvir ( English Sofosbuvir , lat. Sofosbuvirum ) is a synthetic antiviral from a group of nucleoside analogues for oral administration. Sophoswvir is developed by the American company «Pharmasset» under the name «Sovaldy», and from 2012, after the purchase of shares «Pharmasset» by «Gilead Sciences», further development and marketing of the drug is conducted «Gilead Sciences». In 2013, the FDA approved the use of Sobobusvir in combination with ribavirin for treatmenthepatitis C caused by hepatitis C 2 and 3 genotypes, as well as for triple therapy with pegylated interferon and ribavirin for the treatment of hepatitis C caused by hepatitis C virus genotypes on the basis of 4 clinical studies of phase III conducted on US territory. In 2014, the FDA also approved the use of Sobobusvir in combination with another antiviral drug ledispavir based on clinical trials conducted in the United States and published on the site of the British magazine The Lancet in November 2013. According to preliminary research results, this combination is highly effective in the treatment of patients infected with the hepatitis C virus genotype 1, which is most common in the United States, Europe and Japan . In 2014, Gilead Sciences entered into an agreement to license seven Indian pharmaceutical companies to the production of generic sophobus viruses and ice — bags in India and their sale in 91 countries of the world. This agreement was criticized by international organizations dealing with the treatment and protection of patients with hepatitis C and AIDS, as such that does not allow patients with hepatitis C in countries that are not included in the list of countries with permission for the sale of generic Sophobusvir, treated as a cheap analogue of the drug. However, already in 2015, the generic drug sofosbuvir is registered in Ukraine and included in the list of medicines procured for budgetary funds., which was not included in the list of countries where the sale of generic soffosburi is allowed. In 2016, the original drug cofosbuvir is registered in Russia , which is also not included in the previous list of countries where the sale of generic soffosburvis is allowed.
Pharmacological properties
Ledipasvir Sofosbuvir is a synthetic antiviral from a group of nucleoside analogues . The mechanism of action of the drug is the formation of an active metabolite of the drug (uridine analogue triphosphate codenamed GS-461203) that inhibits the NS5B RNA polymerase of the hepatitis C virus and inhibits the replication of hepatitis C virus genotypes C 1, 2, 3 and 4 (according to in vitro data , cofosburir inhibits the replication of viruses and also 5 and 6 genotypes that are less common). [2] Sophosbuvir, as well as other RNA-polymerase inhibitors of the hepatitis C virus, have high resistance to the development of tolerance of the virus to the dasg compared to other antiviral drugs (in particular, protease inhibitors ), in which the ineffectiveness of hepatitis C treatment is more often observed. The active metabolite of the GS-461203 sofosbuvir is not an inhibitor of human RNA and DNA polymerase , nor does it inhibit mitochondrial RNA polymerase. Cofosbuvir can be effectively used in combination with ribavirin in dual therapy or in combination with ribavirin and pegylated interferon alfa-2a in triple hepatitis C therapy, as well as in combination with another nucleotide analogue of lidipasum ( NS5A RNA inhibitor)) (including in cases of ineffectiveness of double or triple therapy of hepatitis C) with less side effects .In addition to fewer side effects, cofosburv has a higher efficacy compared to previously synthesized antiviral drugs, and also requires a 2-4 times shorter term for effective elimination of hepatitis C.
Pharmacokinetics
Sophosbuvir is rapidly absorbed when administered orally, the bioavailability of the drug is 92%. The maximum concentration of cofosburir in the blood is achieved within 0.5-2 hours after taking the drug. Sophosbuvir is rapidly metabolized to the formation of an inactive metabolite codenamed GS-331007, the maximum concentration of which is achieved within 2-4 hours after oral administration of the cofosburir. Receiving a cofosburive with a greasy food slows the absorption of the drug, but increases the volume of its absorption. Sophosbuvir is good, 85% bound to plasma proteins [2] (according to the company’s main manufacturer, protein binding is 61-65% ) The inactive metabolite of sofosbuvir concentrates in the liver where it is metabolized to the formation of an active metabolite code-named GS-461203 by hydrolyzing the part of the carboxylic acid ether with the cleavage of phosphoramidate with a protein that binds the trivalent hostnucleotide 1 (HINT1), which is followed by phosphorylation to form the pyrimidine nucleotide. Sophosphivir from the body is excreted predominantly (80%) with urine in the form of metabolites, partly excreted by feces. In a small amount is also displayed with exhaled air. The half-life of cofosbuviruses is on average 24 minutes (0.4 hours) for the main drug and 27 hours for the main metabolite, data for the increase of this time in the liver andrenal insufficiency , as well as the elderly, is not.
