{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T03:24:48Z","timestamp":1770780288592,"version":"3.50.0"},"reference-count":11,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vatiquinone is a small molecule inhibitor of 15\u2010lipoxygenase in development for patients with Friedreich's ataxia. The objective of this analysis was to determine the effect of a cytochrome P450 isoform 3A4 (CYP3A4) inhibitor and inducer on vatiquinone pharmacokinetics (PKs). The coadministration of 400\u00a0mg of vatiquinone with 200\u00a0mg of itraconazole (a CYP3A4 inhibitor) resulted in increased maximum observed concentration (C<jats:sub>max<\/jats:sub>) of vatiquinone and systemic exposure (AUC<jats:sub>0\u2010inf<\/jats:sub>) by approximately 3.5\u2010 and 2.9\u2010fold, respectively. The coadministration of 400\u00a0mg of vatiquinone with 600\u00a0mg of rifampin (a CYP3A4 inducer) resulted in decreased vatiquinone C<jats:sub>max<\/jats:sub> and AUC<jats:sub>0\u2010inf<\/jats:sub> by approximately 0.64\u2010 and 0.54\u2010fold, respectively. The terminal half\u2010life of vatiquinone was not affected by itraconazole or rifampin. These clinical study results confirm the in vitro reaction phenotyping data that shows that CYP3A4 plays an important role in vatiquinone metabolism. The result of this analysis together with phase 3 efficacy and safety data, population PK analysis, and the exposure\u2010response relationship will determine if the extent of vatiquinone changes in the presence of CYP3A4 inhibitors and inducers are considered clinically relevant.<\/jats:p>","DOI":"10.1002\/cpdd.1461","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T12:58:09Z","timestamp":1723467489000},"page":"1283-1290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effect of Itraconazole, a CYP3A4 Inhibitor, and Rifampin, a CYP3A4 Inducer, on the Pharmacokinetics of Vatiquinone"],"prefix":"10.1002","volume":"13","author":[{"given":"Lucy","family":"Lee","sequence":"first","affiliation":[{"name":"PTC Therapeutics, Inc. 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