{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:10:47Z","timestamp":1770509447490,"version":"3.49.0"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,2,4]],"date-time":"2009-02-04T00:00:00Z","timestamp":1233705600000},"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":[[2009,5]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003<jats:italic>Schisandra sphenanthera<\/jats:italic>extract (SchE) and tacrolimus are often co\u2010administered in treating renal and liver transplant recipients in China.<\/jats:p><jats:p>\u2022\u2003Our previous study has demonstrated that SchE can increase the oral bioavailability of tacrolimus.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003The results of this study show that SchE can markedly increase the blood concentration and oral bioavailability of midazolam in healthy volunteers.<\/jats:p><jats:p>\u2022\u2003This finding suggests that SchE may be an inhibitor of CYP3A and is likely to alter the disposition of drugs that are metabolized by CYP3A.<\/jats:p><jats:p><jats:bold>AIMS<\/jats:bold>To assess the effect of<jats:italic>Schisandra sphenanthera<\/jats:italic>extract (SchE) on the pharmacokinetics of midazolam, a probe drug of CYP3A, and its metabolite 1\u2032\u2010hydroxy midazolam in healthy volunteers.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold>Twelve healthy male volunteers were orally treated with SchE, three capsules twice daily for 7 days. Pharmacokinetic investigations of oral midazolam administration at 15\u2003mg were performed both before and at the end of the SchE treatment period. The plasma midazolam and 1\u2032\u2010hydroxy midazolam concentrations were determined by high\u2010performance liquid chromatography\u2013tandem mass spectrometry. Estimated pharmacokinetic parameters before and with SchE were calculated with noncompartmental techniques.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold>Following administration of SchE, the average increases (%) of individual increases in AUC, AUMC and<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>of midazolam were 119.4% [95% confidence interval (CI) 83.9, 155.0], 183.4% (95% CI 120.5, 246.2) and 85.6% (95% CI 14.4, 156.9), respectively (<jats:italic>P<\/jats:italic>&lt; 0.01 or 0.05). On average, there was a 133.3% (95% CI 8.9, 257.7) increase in midazolam<jats:italic>t<\/jats:italic><jats:sub>max<\/jats:sub>(<jats:italic>P<\/jats:italic>&lt; 0.01). The average decrease (%) in CL\/<jats:italic>F<\/jats:italic>was 52.1% (95% CI 44.9, 59.4) (<jats:italic>P<\/jats:italic>&lt; 0.01). No significant changes were seen in midazolam half\u2010life. After co\u2010administration of SchE, the average increase (%) in<jats:italic>t<\/jats:italic><jats:sub>max<\/jats:sub>of 1\u2032\u2010hydroxy midazolam was 150.0% (95% CI 22.2, 277.8) (<jats:italic>P<\/jats:italic>&lt; 0.05). No significant differences were observed in the other pharmacokinetic parameters of 1\u2032\u2010hydroxy midazolam.<\/jats:p><jats:p><jats:bold>CONCLUSIONS<\/jats:bold>SchE can markedly increase the oral bioavailability of midazolam in healthy volunteers. SchE is an inhibitor of CYP3A and has a high susceptibility to alter the disposition of drugs metabolized by CYP3A.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2009.03383.x","type":"journal-article","created":{"date-parts":[[2009,2,4]],"date-time":"2009-02-04T10:49:20Z","timestamp":1233744560000},"page":"541-546","source":"Crossref","is-referenced-by-count":29,"title":["Effects of<i>Schisandra sphenanthera<\/i>extract on the pharmacokinetics of midazolam in healthy volunteers"],"prefix":"10.1111","volume":"67","author":[{"given":"Hua\u2010Wen","family":"Xin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Chun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai\u2010Rong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,4,24]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.60.3.0012"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.06.036"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2006.03.009"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.000646"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.9.4.635"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200721030-00001"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.22.328"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53221-X"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2007.02922.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199408000-00001"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2003.23"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.129068"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1177\/00912700222011418"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)73227-X"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1211\/0022357044021"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/acm.2005.11.433"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.FP0061311"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-9236(95)90068-3"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-197601020-00005"},{"key":"e_1_2_6_21_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0022-3565(25)22834-8","article-title":"Use of midazolam as a human cytochrome P4503A probe: I: in vitro\u2013in vivo correlations in liver transplant patients","volume":"271","author":"Thummel KE","year":"1994","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_22_2","first-page":"634","article-title":"Single plasma sampling to predict oral clearance of CYP3A probe midazolam","volume":"22","author":"Zhu B","year":"2001","journal-title":"Acta Pharmacol Sin"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018877803319"},{"key":"e_1_2_6_24_2","first-page":"110","article-title":"Relationship between hepatic cytochrome P450 3A content and activity and the disposition of midazolam administered orally","volume":"26","author":"Wandel C","year":"1998","journal-title":"Drug Metab Dispos"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2125.2009.03383.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2125.2009.03383.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T11:08:00Z","timestamp":1738926480000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2125.2009.03383.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,24]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2009,5]]}},"alternative-id":["10.1111\/j.1365-2125.2009.03383.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2125.2009.03383.x","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4,24]]}}}