{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:37:11Z","timestamp":1773005831142,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T00:00:00Z","timestamp":1757116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PTC Therapeutics, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Introduction: Vatiquinone is a first-in-class, small molecule designed to maintain mitochondrial function in the disorders like Friedreich\u2019s ataxia (FA). Vatiquinone inhibits 15-lipoxygenase, consequently decreasing oxidative stress and neuroinflammatory response pathways. Methods: Population pharmacokinetic modeling analysis was conducted to characterize vatiquinone pharmacokinetic profiles in healthy volunteers and patients and explore the effects of covariates on vatiquinone exposures. Results: A two-compartment model with parallel zero- and first-order absorption was developed and verified. The values of essential parameters were: absorption fraction through the first-order process, 74.4%; absorption rate constant, 0.20 h\u22121; delay time, 2.79 h; zero-order absorption duration, 6.03 h; apparent volume of distribution, 180.75 L for the central and 4852.69 L for the peripheral compartment; and apparent clearance, 162.72 L\/h. Strong CYP3A4 inducers could reduce exposure by 50%; strong CYP3A4 inhibitors could increase it by 252%. Vatiquinone exposure was 19% lower in patients with Friedreich\u2019s ataxia versus healthy volunteers. A medium-fat meal increased exposure up to 25-fold versus a fasted status. Body weight and body mass index had significant clinical relevance to exposures. Conclusions: A two-compartment model effectively described the pharmacokinetic profiles of vatiquinone after oral administration. Covariates significantly impacted exposures, including body weight, meals, disease status, comedications and body mass index.<\/jats:p>","DOI":"10.3390\/ph18091339","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T08:06:32Z","timestamp":1757318792000},"page":"1339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterizing Population Pharmacokinetics of Vatiquinone in Healthy Volunteers and Patients with Friedreich\u2019s Ataxia"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1883-0868","authenticated-orcid":false,"given":"Yongjun","family":"Hu","sequence":"first","affiliation":[{"name":"PTC Therapeutics, Warren, NJ 07059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2528-7656","authenticated-orcid":false,"given":"Lan","family":"Gao","sequence":"additional","affiliation":[{"name":"PTC Therapeutics, Warren, NJ 07059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Lee","sequence":"additional","affiliation":[{"name":"PTC Therapeutics, Warren, NJ 07059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan J.","family":"Cherry","sequence":"additional","affiliation":[{"name":"PTC Therapeutics, Warren, NJ 07059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4692-7499","authenticated-orcid":false,"given":"Ronald","family":"Kong","sequence":"additional","affiliation":[{"name":"PTC Therapeutics, Warren, NJ 07059, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,6]]},"reference":[{"key":"ref_1","unstructured":"NORD (2025, July 04). 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