{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T09:57:31Z","timestamp":1783763851862,"version":"3.55.0"},"reference-count":0,"publisher":"Walter de Gruyter GmbH","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Metabolism and Drug Interactions"],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"Abstract<\/jats:title>\n \n Background:<\/jats:bold>\n Midazolam apparent oral clearance (CL\n ORAL<\/jats:sub>\n ) is used to estimate intestinal and hepatic cytochrome P450 (CYP) 3A activity. A limited sampling approach was performed to access a midazolam partial area under the concentration time curve (AUC) to estimate CL\n ORAL<\/jats:sub>\n .\n <\/jats:p>\n \n Methods:<\/jats:bold>\n Midazolam plasma concentrations from healthy adults were obtained during CYP3A baseline (n=116), inhibition (n=75), and induction or activation (n=66) from seven published studies. Observed CL\n ORAL<\/jats:sub>\n and partial AUCs of AUC\n 0-2<\/jats:sub>\n , AUC\n 0-4<\/jats:sub>\n , AUC\n 0-6<\/jats:sub>\n , AUC\n 1-2<\/jats:sub>\n , AUC\n 1-4<\/jats:sub>\n , AUC\n 2-4<\/jats:sub>\n , and AUC\n 2-6<\/jats:sub>\n were determined by noncompartmental analysis. Subject data were randomly divided into a training set and a validation set. Linear regression equations, derived from partial AUCs, were developed from training set data. Predicted CL\n ORAL<\/jats:sub>\n was determined from these equations from validation set data. Preset criterion was a coefficient of determination (\n r<\/jats:italic>\n 2<\/jats:sup>\n ) greater than or equal to 0.9. Bias and precision were evaluated by relative percent mean prediction error (%MPE) and relative percent mean absolute error (%MAE).\n <\/jats:p>\n \n Results:<\/jats:bold>\n During CYP3A baseline conditions, all of the evaluated CL\n ORAL<\/jats:sub>\n equations had unacceptable\n r<\/jats:italic>\n 2<\/jats:sup>\n (range: 0.34\u20130.86). During CYP3A inhibition, all of the evaluated CL\n ORAL<\/jats:sub>\n equations had unacceptable %MAE. Acceptable\n r<\/jats:italic>\n 2<\/jats:sup>\n , %MPE, and %MAE were observed during CYP3A induction\/activation with AUC\n 0-4<\/jats:sub>\n (\n r<\/jats:italic>\n 2<\/jats:sup>\n =0.99, %MPE=3.9, %MAE=12.5) and AUC\n 1-4<\/jats:sub>\n (\n r<\/jats:italic>\n 2<\/jats:sup>\n =0.99, %MPE=6%, %MAE=11.1%). The same equations also predicted the extent of CYP3A induction as a lack of equivalence was observed with AUC\n 0-4<\/jats:sub>\n and AUC\n 1-4<\/jats:sub>\n .\n <\/jats:p>\n \n Conclusions:<\/jats:bold>\n Midazolam partial AUCs were unable to estimate CYP3A activity during the evaluated baseline and inhibitory conditions. Midazolam CL\n ORAL<\/jats:sub>\n utilizing a partial AUC\n 0-4<\/jats:sub>\n and AUC\n 1-4<\/jats:sub>\n was able to estimate CYP3A induction with rifampin and Ginkgo biloba extract.\n <\/jats:p>","DOI":"10.1515\/dmdi-2013-0040","type":"journal-article","created":{"date-parts":[[2013,10,10]],"date-time":"2013-10-10T13:34:02Z","timestamp":1381412042000},"page":"217-223","source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of partial area under the concentration time curve to estimate midazolam apparent oral clearance for cytochrome P450 3A phenotyping"],"prefix":"10.1515","volume":"28","author":[{"given":"Wei","family":"Tai","sequence":"first","affiliation":[{"name":"University of California, San Diego (UCSD), Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheryl L.","family":"Gong","sequence":"additional","affiliation":[{"name":"University of California, San Diego (UCSD), Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley M.","family":"Tsunoda","sequence":"additional","affiliation":[{"name":"University of California, San Diego (UCSD), Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard E.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Christopher","family":"Gorski","sequence":"additional","affiliation":[{"name":"Mylan Pharmaceuticals, Inc., Morgantown, WV, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott R.","family":"Penzak","sequence":"additional","affiliation":[{"name":"Warren G. Magnuson Clinical Center, Pharmacy Department, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Aubrey","family":"Stoch","sequence":"additional","affiliation":[{"name":"Merck and Company, Inc., Rahway, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Ma","sequence":"additional","affiliation":[{"name":"University of California, San Diego (UCSD), Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2013,10,11]]},"container-title":["dmdi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/dmdi-2013-0040\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/dmdi-2013-0040\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T07:43:44Z","timestamp":1765525424000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/dmdi-2013-0040\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,11]]},"references-count":0,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2013,11,23]]},"published-print":{"date-parts":[[2013,12,1]]}},"alternative-id":["10.1515\/dmdi-2013-0040"],"URL":"https:\/\/doi.org\/10.1515\/dmdi-2013-0040","relation":{},"ISSN":["2191-0162","0792-5077"],"issn-type":[{"value":"2191-0162","type":"electronic"},{"value":"0792-5077","type":"print"}],"subject":[],"published":{"date-parts":[[2013,10,11]]}}}