{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:23:45Z","timestamp":1792268625033,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T00:00:00Z","timestamp":1692662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>This study evaluated the effects of SHR0302 on the pharmacokinetics of cytochrome P450 (CYP) probe substrates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a single\u2010centre, open\u2010label, three\u2010period drug\u2013drug interaction (DDI) study in 24 healthy subjects (NCT05392127). Subjects received a single oral dose of 5\u00a0mg warfarin (CYP2C9), 20\u2009mg omeprazole (CYP2C19) and 15\u2009mg midazolam (CYP3A4) on Days 1, 8 and 22, and received 0.5\u00a0mg repaglinide (CYP2C8) on Days 7, 14 and 28. Multiple oral doses of 8\u00a0mg SHR0302 were administered once daily from Day 8 to Day 28.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The exposure of S\u2010warfarin and repaglinide were comparable before and after SHR0302 administration. AUC of midazolam was not affected by SHR0302, whereas the administration of SHR0302 slightly decreased the <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> of midazolam by 7.6% (single dose) and 15.7% (once daily for 14\u2009days). The AUC<jats:sub>0\u2010<jats:italic>t<\/jats:italic><\/jats:sub>, AUC<jats:sub>0\u2010inf<\/jats:sub>, and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> of omeprazole were slightly decreased after a single dose of SHR0302 by 19.2%, 21.8% and 23.5%, respectively. In the presence of SHR0302 for 14\u2009days, the AUC<jats:sub>0\u2010<jats:italic>t<\/jats:italic><\/jats:sub>, AUC<jats:sub>0\u2010inf<\/jats:sub>, and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> of omeprazole were marginally reduced by 3.0%, 16.4% and 8.3%, respectively. According to the induction mechanism of the CYP enzyme, for the investigation of the induction effect, the results of multiple administrations of the perpetrator were more reliable than those of the single dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results demonstrated that co\u2010administration of SHR0302 8\u00a0mg once daily is unlikely to have a clinically meaningful effect on the exposure of drugs metabolized by CYP3A4, CYP2C8, CYP2C9 and CYP2C19 in healthy subjects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15856","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T07:08:18Z","timestamp":1689750498000},"page":"3659-3668","source":"Crossref","is-referenced-by-count":3,"title":["Effect of SHR0302 on the pharmacokinetics of CYP3A4, CYP2C8, CYP2C9 and CYP2C19 probe substrates in healthy volunteers: A cocktail analysis"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1687-9816","authenticated-orcid":false,"given":"Meng","family":"Fu","sequence":"first","affiliation":[{"name":"Jiangsu Hengrui Pharmaceuticals Co., Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Luo","sequence":"additional","affiliation":[{"name":"Clinical Trail Center Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Feng","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Pharmaceuticals Co., Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongda","family":"Lin","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Pharmaceuticals Co., Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zekun","family":"Lu","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Pharmaceuticals Co., Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Gu","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Pharmaceuticals Co., Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Fan","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Pharmaceuticals Co., Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wu","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Pharmaceuticals Co., Ltd.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Huang","sequence":"additional","affiliation":[{"name":"Clinical Trail Center Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Shen","sequence":"additional","affiliation":[{"name":"Jiangsu Hengrui Pharmaceuticals Co., Ltd.  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