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We aimed to offer specific recommendations for CYP3A DDI clinical trial design. This was an open, three\u2010cycle, self\u2010controlled study. Healthy subjects were given different administration strategies of CYP3A4 perpetrators. In each cycle, blood samples were collected before and within 24\u2009h after the administration of midazolam, the CYP3A indicator substrate. The plasma concentrations\u00a0of midazolam and 1\u2010hydroxymidazolam was obtained using liquid chromatography tandem mass spectrometry assay. For CYP3A inhibition, itraconazole exposure with a loading dose could increase the exposure of midazolam by 3.21\u2010fold based on maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>), 8.37\u2010fold based on area under the curve Pharmacology Research &amp; Perspectives for review only from zero to the time point (AUC<jats:sub>0\u2013t<\/jats:sub>), and 11.22\u2010fold based on area under the curve from zero to infinity (AUC<jats:sub>0\u2013\u221e<\/jats:sub>). The data were similar for itraconazole pretreatment without a loading dose. For CYP3A induction, the exposure of rifampin for 7\u2009days decreased the plasma concentration of midazolam ~0.27\u2010fold based on <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, ~0.18\u2010fold based on AUC<jats:sub>0\u2013t<\/jats:sub>, and ~0.18\u2010fold based on AUC<jats:sub>0\u2013\u221e<\/jats:sub>. Midazolam exposure did not significantly change when the pretreatment of rifampin increased to 14\u2009days. This study showed that itraconazole pretreatment for 3\u2009days without a loading dose was enough for CYP3A inhibition, and pretreatment with rifampin for 7\u2009days could induce near\u2010maximal CYP3A levels.<\/jats:p>","DOI":"10.1002\/prp2.1252","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T06:13:39Z","timestamp":1722233619000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An open\u2010label study to explore the optimal design of <scp>CYP3A<\/scp> drug\u2013drug interaction clinical trials in healthy Chinese people"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1199-9599","authenticated-orcid":false,"given":"Jingcheng","family":"Chen","sequence":"first","affiliation":[{"name":"Research Ward, Beijing Friendship Hospital Capital Medical University  Beijing 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