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Absorption increased markedly with fatty meals, with mean AUC values 22-fold for solid fatty meals and 3-fold for liquid meals versus fasting, alongside reduced intersubject variability. Under TID dosing, pharmacokinetic profiles showed three peaks on Day 1 and Day 6; AUC and Cmax increased dose-proportionally from 200 to 400 mg. Accumulation ratios on Day 6 supported a convenient TID regimen with fatty meals.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/biopharmaceutics-drug-disposition-enhanced-vatiquinone-bioavailability-with-fatty-meals-and-optimal-dosing-schedule/416174/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/biopharmaceutics-drug-disposition-enhanced-vatiquinone-bioavailability-with-fatty-meals-and-optimal-dosing-schedule/416174.png","ImageObject",300,407,{"name":92,"@type":93},"Stanley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does a fatty meal affect vatiquinone absorption?","Question",{"text":112,"@type":113},"Absorption is significantly enhanced when vatiquinone is administered with fatty meals, with much higher mean AUC values compared with fasting. Inter-subject variability for AUC appears lower with fatty meals.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What pharmacokinetic pattern is observed with TID dosing?",{"text":117,"@type":113},"Typical individual concentration-time profiles show three peaks on Day 1 and after multiple dosing on Day 6. Exposures (AUC and Cmax) increase from 200 to 400 mg in a dose-proportional manner.",{"name":119,"@type":110,"acceptedAnswer":120},"What do the findings support regarding how vatiquinone should be taken?",{"text":121,"@type":113},"Both studies support administering vatiquinone TID with fatty meals using a convenient dosing schedule. Day 6 accumulation ratios further support the regimen’s exposure profile.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},416174,1790719036,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":46,"preview_page_count":4},2336477405376,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Biopharmaceutics & Drug Disposition  \nEnhanced Vatiquinone Bioavailability With Fatty Mealsand Optimal Dosing Schedule  \nLucy Lee  | Katsuyuki Murase  | Martin Thoolen | Peter Giannousis  | Diksha Kaushik  | Lee Golden | Ronald Kong   \nPTC Therapeutics Inc., Warren, New Jersey, USA Correspondence: Ronald Kong ([rkong@ptcbio.com](rkong@ptcbio.com))  \nReceived: 4 October 2024 | Revised: 25 April 2025 | Accepted: 22 August 2025  \nFunding: The authors received no specific funding for this work.  \nKeywords: bioavailability | dosing regimen | food effect | rare disease  \nABSTRACT  \nVatiquinone, a 15‐lipoxygenase (LO) inhibitor, is an orally bioavailable small molecule being developed for the treatment of Friedreich's ataxia, a disorder characterized by high levels of oxidative stress and dysregulation of energy metabolism. This investigation discusses the results of the food effect and three times a day (TID) dosing schedule studies data. The food effect study showed that absorption is significantly enhanced when vatiquinone was administered with fatty meals, either solid or liquid. Mean vatiquinone area under the concentration‐time curve (AUC) values were 22‐fold and 3‐fold higher in subjects who consumed fatty meals and liquid meals, respectively, compared with subjects who fasted. With fatty meals, the intersubject variabilities appeared lower for AUC. The TID dosing study showed that the typical individual pharmacokinetic concentration profile exhibited 3 peaks on both Day 1 and after multiple dosing on Day 6. Vatiquinone exposures, AUC, and maximum concentration (Cmax) appeared to increase from 200 to 400 mg in a dose‐proportional manner with moderate variabilities, ranging from approximately 35% to 65%. The mean Day 6 accumulation ratio (ARAUC) suggested an accumulation ratio of 1.61 and 1.73 for 200 and 400 mg, respectively. The results of both studies support the recommendation of administering vatiquinone TID with fatty meals taken on a convenient dosing regimen.  \n1 | Introduction  \nVatiquinone (PTC743, EPI‐743, alpha‐tocotrienol quinone) is an orally bioavailable small molecule being developed by PTC Therapeutics for the treatment of Friedreich's ataxia, a disorder characterized by high levels of oxidative stress and dysregulation of energy metabolism (Ennsetal. 2012). High levels of oxygen free radicals can cause an accumulation of lipid peroxides and the depletion of reduced glutathione (GSH; Riederer et al. 1989; Piemonte et al. 2001), triggering a feed‐forward cycle that promotes proinflammatory signaling, additional increases in oxidative stress, and, ultimately, cell death through ferroptosis (Guineyet al. 2017) . Vatiquinone is a potent inhibitor of 15‐lipoxygenase (15‐LO), a key enzyme responsible for the formation of lipid  \nperoxides. Inhibition of 15‐LO blocks the accumulation of lipid peroxides and prevents the depletion of GSH, which, in turn, prevents proinflammatory signals, preserves cellular function, and promotes cell survival. In clinical studies, vatiquinone has been found to increase GSH levels and decrease the ratio of oxidized GSH to reduced GSH (OX/GSH), correlating with clinical improvement in disease symptoms and the arrest or reversal of disease progression (Blankenberg et al. 2012; Pastoreet al. 2013) . The critical role of 15‐LO as a key enzyme in the biological process of ferroptosis has been implicated in central nervous system diseases (Joshi et al. 2015; Guiney et al. 2017) .  \nVatiquinone crosses the blood–brain barrier and promotes its pharmacological activities by inhibiting 15‐LO (Pastore  \nThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.  \n© 2025 PTC Therapeutics, Inc. Biopharmaceutics & Drug Disposition published by John Wiley & Sons Ltd.  \nBiopharmaceut","cbCailrtWGBaeFyQ","https://ap.wps.com/l/cbCailrtWGBaeFyQ","pdf",912633,"English","# Introduction\n## Food effect and TID dosing study results\n## Pharmacokinetics, exposure, and accumulation\n## Mechanistic background and clinical context","[{\"question\":\"How does a fatty meal affect vatiquinone absorption?\",\"answer\":\"Absorption is significantly enhanced when vatiquinone is administered with fatty meals, with much higher mean AUC values compared with fasting. Inter-subject variability for AUC appears lower with fatty meals.\"},{\"question\":\"What pharmacokinetic pattern is observed with TID dosing?\",\"answer\":\"Typical individual concentration-time profiles show three peaks on Day 1 and after multiple dosing on Day 6. Exposures (AUC and Cmax) increase from 200 to 400 mg in a dose-proportional manner.\"},{\"question\":\"What do the findings support regarding how vatiquinone should be taken?\",\"answer\":\"Both studies support administering vatiquinone TID with fatty meals using a convenient dosing schedule. Day 6 accumulation ratios further support the regimen’s exposure profile.\"}]","Biopharmaceutics & Drug Disposition - Enhanced Vatiquinone Bioavailability With Fatty Meals and Optimal Dosing Schedule | PDF",1790604404]