{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T06:29:47Z","timestamp":1771655387109,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,12,24]],"date-time":"2001-12-24T00:00:00Z","timestamp":1009152000000},"content-version":"vor","delay-in-days":449,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2000,10]]},"abstract":"<jats:p> <jats:bold>\n            <jats:italic>Aims<\/jats:italic>\n          <\/jats:bold>\u2002To characterize the effect of an oral contraceptive (OC) containing ethinylestradiol and gestodene on the activity of CYP3A4 <jats:italic>in vivo<\/jats:italic> as measured by the 1\u2032\u2010hydroxylation of midazolam.<\/jats:p><jats:p> <jats:bold>\n            <jats:italic>Methods<\/jats:italic>\n          <\/jats:bold>\u2002In this randomised, double\u2010blind, cross\u2010over trial nine healthy female subjects received either a combined OC (30\u2003\u00b5g ethinylestradiol and 75\u2003\u00b5g gestodene) or placebo once daily for 10\u2003days. On day 10, a single 7.5\u2003mg dose of midazolam was given orally. Plasma concentrations of midazolam and 1\u2032\u2010hydroxymidazolam were determined up to 24\u2003h and the effects of midazolam were measured with three psychomotor tests up to 8\u2003h.<\/jats:p><jats:p> <jats:bold>\n            <jats:italic>Results<\/jats:italic>\n          <\/jats:bold>\u2002The combined OC increased the mean AUC of midazolam by 21% (95% CI 2% to 40%; <jats:italic>P<\/jats:italic>\u2003=\u20030.03) and decreased that of 1\u2032\u2010hydroxymidazolam by 25% (95% CI 10% to 41%; <jats:italic>P<\/jats:italic>\u2003=\u20030.01), compared with placebo. The metabolic ratio (AUC of 1\u2032\u2010hydroxymidazolam\/AUC of midazolam) was 36% smaller (95% CI 19% to 53%; <jats:italic>P<\/jats:italic>\u2003=\u20030.01) in the OC phase than in the placebo phase. There were no significant differences in the <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, <jats:italic>t<\/jats:italic><jats:sub>max<\/jats:sub>, <jats:italic>t<\/jats:italic><jats:sub>\u00bd<\/jats:sub> or effects of midazolam between the phases.<\/jats:p><jats:p> <jats:bold>\n            <jats:italic>Conclusions<\/jats:italic>\n          <\/jats:bold>\u2002A combined OC preparation caused a modest reduction in the activity of CYP3A4, as measured by the 1\u2032\u2010hydroxylation of midazolam, and slightly increased the AUC of oral midazolam. This study suggests that, at the doses used, ethinylestradiol and gestodene have a relatively small effect on CYP3A4 activity <jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1046\/j.1365-2125.2000.00271.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T04:39:49Z","timestamp":1047357589000},"page":"333-337","source":"Crossref","is-referenced-by-count":66,"title":["Effect of an oral contraceptive preparation containing ethinylestradiol and gestodene on CYP3A4 activity as measured by midazolam 1\u2032\u2010hydroxylation"],"prefix":"10.1111","volume":"50","author":[{"given":"Sanna","family":"Palovaara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kari T.","family":"Kivist\u00f6","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasi","family":"Tapanainen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pekka","family":"Manninen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pertti J.","family":"Neuvonen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kari","family":"Laine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,4,20]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(90)90431-P"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx00016a015"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(91)90129-S"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1984.240"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1991.29"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)80009-9"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199018060-00004"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-199309010-00003"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00891.x"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1981.217"},{"key":"e_1_2_5_12_2","first-page":"89","article-title":"Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4","volume":"36","author":"Kronbach T","year":"1989","journal-title":"Mol Pharmacol"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(94)90543-6"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1992.84"},{"key":"e_1_2_5_15_2","first-page":"549","article-title":"Use of midazolam as a human cytochrome P450 3A probe: I. In vitro\u2013in vivo","volume":"271","author":"Thummel KE","year":"1994","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_16_2","first-page":"557","article-title":"Use of midazolam as a human cytochrome P450 3A probe: II. Characterization of inter\u2013 and intraindividual hepatic CYP3A variability after liver transplantation","volume":"271","author":"Thummel KE","year":"1994","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1993.25"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/004982598238886"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)82865-0"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1980.tb01745.x"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1994.60"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1996.tb04251.x"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018877803319"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(90)90560-T"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1390167"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(93)90043-7"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050543"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91988-X"},{"key":"e_1_2_5_29_2","first-page":"19","article-title":"Metabolism of cyclosporine","volume":"17","author":"Maurer G","year":"1985","journal-title":"Transplant Proc"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1988.tb05759.x"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2125.2000.00271.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2125.2000.00271.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1365-2125.2000.00271.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T06:46:14Z","timestamp":1698561974000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1046\/j.1365-2125.2000.00271.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,10]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2000,10]]}},"alternative-id":["10.1046\/j.1365-2125.2000.00271.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1365-2125.2000.00271.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":[[2000,10]]}}}