{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:58:02Z","timestamp":1790035082115,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cytochrome P450 (CYP) 3A plays a significant role in fruquintinib metabolism in vitro. This 2\u2010part, 2\u2010period fixed\u2010sequence study investigated the impact of CYP3A inhibition (itraconazole) and CYP3A induction (rifampin) on the pharmacokinetics (PK) of fruquintinib and M11, its main metabolite. Fourteen healthy subjects in each part received a single dose of fruquintinib 5\u00a0mg alone in Period 1 and with itraconazole (Part A) or rifampin (Part B) in Period 2 under fasted conditions. Itraconazole or rifampin was administered daily 4 or 7 days before coadministration, respectively; administration of both continued throughout the PK sampling period. PK samples were collected before dosing and over 168 hours after fruquintinib dosing. Coadministration with itraconazole resulted in an increase of fruquintinib systemic exposure, determined by area under the plasma concentration\u2010time curves (AUCs) by approximately 10%. Decreases in M11 AUCs and maximum plasma concentration (C\n                    <jats:sub>max<\/jats:sub>\n                    ) ranged from 44% to 55% but were not considered clinically meaningful. Rifampin reduced fruquintinib C\n                    <jats:sub>max<\/jats:sub>\n                    and AUCs by 12% and 65%, respectively. Rifampin had a marginal effect on M11 AUCs and increased M11 C\n                    <jats:sub>max<\/jats:sub>\n                    by 2.3\u2010fold. Data support that concomitant use of fruquintinib with potent CYP3A inducers of rifampin\u2010like potency should be avoided, but no dose adjustment is recommended when coadministered with CYP3A inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.1520","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T09:25:30Z","timestamp":1747214730000},"page":"605-613","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of Potential Effects of CYP3A Inhibition and CYP3A Induction on the Pharmacokinetics of Fruquintinib in Healthy Subjects"],"prefix":"10.1002","volume":"14","author":[{"given":"Martha","family":"Gonzalez","sequence":"first","affiliation":[{"name":"HUTCHMED International Corporation  Florham Park NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Yang","sequence":"additional","affiliation":[{"name":"HUTCHMED International Corporation  Florham Park NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R","family":"Schelman","sequence":"additional","affiliation":[{"name":"HUTCHMED International Corporation  Florham Park NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc. 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