{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:33:58Z","timestamp":1791920038724,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":2319,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:p>Human pregnane X receptor (hPXR) gene polymorphisms (spanning exon 2 to exon 5) and alternative mRNA splicing were investigated as possible contributors to individual variability in CYP3A metabolic activity measured both in vivo and in vitro. None of the 9 variants evaluated, including the 2 most common nonsynonymous variants (Pro27Ser and Gly36Arg), was found to be associated with midazolam 1\u2032\u2010hydroxylation rate measured in a bank of human livers (48 European Americans, 4 African Americans, 2 Hispanics). In contrast, 3 linked hPXR variants (g.252A&gt;G, g.275A&gt;G, and g.4760G&gt;A) were significantly (P &lt; .05) associated with oral midazolam clearance in a mixed race\/ethnicity population (n = 26) and the African American subpopulation (n = 14) but not in European Americans (n = 9). Although the amount of hPXR mRNA normally spliced at the exon 4\u20135 junction correlated well with midazolam 1\u2032\u2010hydroxylation activities (P &lt; .05), none of the 6 hPXR mRNA splice variants identified was associated with midazolam 1\u2032\u2010hydroxylation. 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