{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:21:56Z","timestamp":1780572116462,"version":"3.54.1"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,8,6]],"date-time":"2012-08-06T00:00:00Z","timestamp":1344211200000},"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":[[2012,9]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Obesity is known to suppress CYP3A4\/5 activity.<\/jats:p><jats:p>\u2022\u2003Use of combined oral contraceptives (COC) has been shown to suppress CYP3A4\/5 activity in non\u2010obese women.<\/jats:p><jats:p>\u2022\u2003However, the effect of COC on CYP3A4\/5 activity is unknown in obese women who constitute 50% of women of reproductive age.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Although we hypothesized that obesity exposure might amplify the impact on CYP3A4\/5 activity in COC users, we found that this was not the case.<\/jats:p><jats:p>\u2022\u2003This finding is reassuring regarding potential additional drug\u2013drug interactions in obese COC users as CYP3A4\/5 is a major player in the metabolism of many marketed drugs.<\/jats:p><jats:p><jats:bold>AIM(S)<\/jats:bold> While it is known that CYP3A4\/5 activity is decreased with combined oral contraceptive (COC) use and obesity suppresses CYP expression, the combined effects of obesity and COC use on CYP3A4\/5 activity are unclear. Therefore, our aim was to examine the effect of COC usage on CYP3A4\/5 activity in obese women.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold> Thirty\u2010four, obese (body mass index, BMI &gt; 30\u2003kg\u2003m<jats:sup>\u22122<\/jats:sup>) women of reproductive age (18\u201335\u2003years old) were placed on a COC pill containing 20\u2003\u00b5g ethinylestradiol\/100\u2003\u00b5g levonorgestrel for 21\u2003days starting at the onset of menses. A midazolam pharmacokinetic study was conducted prior to initiation and after 21\u2003days of COC treatment. Serial blood samples were collected and plasma concentrations of midazolam were measured using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were estimated using a non\u2010compartmental method.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold> Midazolam clearance, a surrogate measure of CYP3A4\/5 activity, was significantly decreased upon COC use (63.3\u2003l\u2003h<jats:sup>\u22121<\/jats:sup><jats:italic>vs<\/jats:italic>. 53.9\u2003l\u2003h<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic> &lt; 0.05). A median decrease of 5.6\u2003l\u2003h<jats:sup>\u22121<\/jats:sup> (95% CI \u22124.1, 13.3\u2003l\u2003h<jats:sup>\u22121<\/jats:sup>) was observed. However, the magnitude of change was similar to that reported in women with normal BMI.<\/jats:p><jats:p><jats:bold>CONCLUSIONS<\/jats:bold> Although we hypothesized that obesity might amplify the impact on CYP3A4\/5 activity in COC users, we found that this was not the case. This finding is reassuring regarding potential additional drug\u2212drug interactions in obese COC users as CYP3A4\/5 is a major enzyme in the metabolism of many marketed drugs.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2012.04209.x","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T15:00:02Z","timestamp":1328194802000},"page":"510-514","source":"Crossref","is-referenced-by-count":10,"title":["Effect of the ethinylestradiol\/levonorgestrel combined oral contraceptive on the activity of cytochrome P4503A in obese women"],"prefix":"10.1111","volume":"74","author":[{"given":"Alison","family":"Edelman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrna","family":"Munar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam 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