letter to the editor<\/a> titled \u201cCovalent Inhibition of Carboxylesterase-2 (CES-2) by Sofosbuvir and its Effect on the Hydrolytic Activation of Tenofovir Disoproxil.\u201d<\/p>\nYan noted that Sovaldi \u2014 and other Hepatitis C medications such as Harvoni and EPCLUSA that contain sofosbuvir \u2014 are often used in combination with additional medications to combat co-infections with other viruses such as HIV and Hepatitis B. Emerging evidence has linked Sovaldi-containing regimens to severe liver and kidney toxicity or reactivation of the other virus. Earlier this year the U.S. Federal Drug Administration ordered placement of the agency\u2019s most prominent warning on these drugs after studies showed they could reactivate Hepatitis B in people who have that virus and Hepatitis C.<\/p>\n
This new study by Yan and Shen shows that sofosbuvir inhibits the hydrolysis (decomposition in water) of tenofovir disoproxil, affecting the drug-activating CES-2 enzyme irreversibly. \u201cThis decreases the therapeutic activation of tenofovir disoproxil with implications of increased kidney toxicity,\u201d Yan said.<\/p>\n
\u201cCES-2 is generally considered as a detoxification enzyme,\u201d Yan said, \u201cit is abundant in the liver and kidney.\u201d \u201cThe enzyme (CES-2) normally breaks down through hydrolysis, activating such medicines as tenofovir disoproxil or inactivating such medicines as aspirin,\u201d he explained. With the enzyme rendered useless by Sovaldi, these medications cannot work fully and can accumulate at toxic levels.<\/p>\n
For now, Yan said doctors should prescribe the medications with instructions to take them at different times or different routes. The HIV medication can be administered first, or through the skin; and the Hepatitis C medication can be taken orally at a later time, he suggested. Yan said clinical trials are needed to fully analyze the impacts of these medications when taken in combination.<\/p>\n","protected":false},"excerpt":{"rendered":"
KINGSTON, R.I., December 13, 2016 \u2014 In the past few years, the normally reticent scientific community heralded as revolutionary new medications for Hepatitis C, saying the drugs would bring a major shift in the treatment of the chronic and potentially fatal viral infection that affects 150 million people worldwide. They were right. These direct-acting drugs, […]<\/p>\n","protected":false},"author":2,"featured_media":72629,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[],"class_list":["post-72628","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-archives"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/posts\/72628","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/comments?post=72628"}],"version-history":[{"count":0,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/posts\/72628\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/media\/72629"}],"wp:attachment":[{"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/media?parent=72628"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/categories?post=72628"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.uri.edu\/news\/wp-json\/wp\/v2\/tags?post=72628"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}