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Effect of Nutraceuticals on Gut Microbiota—What Is the Deal in Cancer?
Published in Sheeba Varghese Gupta, Yashwant V. Pathak, Advances in Nutraceutical Applications in Cancer, 2019
Andréa Burgess, Asra Sami, Sheeba Varghese Gupta
Moreover, a lack of comprehension regarding microbiota metabolism can have lethal consequences. In Japan, the co-administration of the antiviral sorivudine and fluoropyrimidine drugs resulted in the suppression of 5-fluorouracil (5-FU) catabolism. It was later determined that an inhibitor for catabolic 5-FU enzymes was created by the gut flora rather than host enzymes and caused 16 deaths over a 40-day period (Nakayama et al., 1997). In further research, the toxic levels of 5-FU were overturned with the administration of antibiotics to reduce gut microbiota prior to use of sorivudine (Pouncey et al., 2018).
General Discussion about Human CYP2D6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Concomitant use of a drug that affects the activity of the same CYP responsible for biotransformation of another drug can lead to significant increases in plasma concentrations and potentially important drug–drug interactions (Ito et al. 1998). Such interactions may be associated with poor tolerability or increased risk for toxicity. On the other hand, for drugs/prodrugs requiring biotransformation via CYP enzymes from an inactive/less active parent compound to a pharmacologically active metabolite, drug interactions may manifest as a reduction in efficacy. Cases of fatal drug interactions have been reported and several prominent drugs (e.g., cerivastatin, mibefradil, sorivudine, and terfenadine) have been withdrawn from the market because of severe adverse reactions related to drug interactions (Li 2001). Both pharmacokinetic and pharmacodynamic components may be involved in these toxic drug interactions. Because of the clinical significance of drug interactions, it is important to identify drugs and compounds in development that may interact with other drugs, and timely identification of such drugs using proper in vitro and in vivo approaches has important implications for drug development (Zhou et al. 2007).
Antiviral Treatment
Published in Marie Studahl, Paola Cinque, Tomas Bergström, Herpes Simplex Viruses, 2017
Brivudin (BVDU) is metabolized in humans to bromovinyluridine (BVU), which possesses significant hepatic toxicity. Sorivudine is safer than BVDU, but was not approved based on the experience of the fatal drug interaction with 5-FU in cancer patients.
Capecitabine for the treatment of pancreatic cancer
Published in Expert Opinion on Pharmacotherapy, 2019
Nauman S. Siddiqui, Amandeep Godara, Margaret M. Byrne, Muhammad Wasif Saif
In addition to warfarin, few other agents warrant revision here. Allopurinol metabolites can lead to the decreased conversion of capecitabine to 5-FU and hence potentially can decrease 5-FU antitumor activity [63]. Consideration should be given to use of alternate agent rather than the continuation of allopurinol while on capecitabine [64]. Cimetidine, an over the counter H2 blocker can decrease the clearance of 5-FU. Therefore, cimetidine should be discontinued or replaced with other anti-acid medications such as ranitidine if necessary [65]. 5-bromovinyluracil, a metabolite of two antivirals agents, named sorivudine and brivudine is known to be a potent inhibitor of DPD. Patients should not receive concurrent therapy with either of these antiviral agents while receiving capecitabine. If a patient has received prior sorivudine or brivudine, then at least four weeks must elapse before the patient receives capecitabine therapy [66]. Finally, capecitabine can lead to higher phenytoin levels in the plasma. Patients on active treatment should b routinely monitored for phenytoin toxicity and drug levels [66].
Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: kinetic and computational studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Huseyin Cavdar, Murat Senturk, Murat Guney, Serdar Durdagi, Gulru Kayik, Claudiu T. Supuran, Deniz Ekinci
5-Fluorouracil (5-FU) is an uracil analogue used as an antineoplastic drug (antimetabolite). 5-FU interferes with DNA synthesis by blocking DNA polymerase and thymidylate synthetase enzymes. 5-FU and its metabolites have several different mechanisms of action. In vivo, 5-FU is converted to the active metabolite 5-fluoroxyuridine monophosphate (5-FUMP); replacing U, 5-FUMP incorporates into RNA and inhibits RNA processing, thereby inhibiting cell growth. Fluoroxyuridine is used to treat malignant neoplasms of the liver and gastrointestinal tract and hepatic metastases. Sorivudine is a uridine derivative with potent antiviral activity against herpes simplex and varicella zoster viruses. Sorivudine acts by inhibiting DNA polymerase by converting it into triphosphate form in cells. Uramustine, a uracil derivative, is an alkylating antineoplastic agent used in lymphatic malignancies that causes mainly gastrointestinal and bone marrow damage12,13. In this study, the in vitro inhibition properties and in silico calculations of these uracil derivatives 2–9 in their interaction with AChE and BuChE were investigated.
Emergence of varicella-zoster virus resistance to acyclovir: epidemiology, prevention, and treatment
Published in Expert Review of Anti-infective Therapy, 2021
Kimiyasu Shiraki, Masaya Takemoto, Tohru Daikoku
Bromovinyl uracil, a sorivudine metabolite, irreversibly binds and inhibits dihydropyrimidine dehydrogenase activity, which degrades 5-fluorouracil (5-FU). When sorivudine was used in patients with cancer treated with 5-FU, the degradation of 5-FU was impaired, and the 5-FU concentration increased and caused severe hematopoietic toxicity, leading to 15 patient deaths because of 5-FU and sorivudine. Therefore, sorivudine has not been used in Japan.