{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:56:32Z","timestamp":1760061392715},"reference-count":11,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2003,9,25]],"date-time":"2003-09-25T00:00:00Z","timestamp":1064448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dextromethorphan is used widely <jats:italic>in vivo<\/jats:italic> to phenotype the polymorphically expressed cytochrome P450 (CYP) 2D6. Also dextromethorphan is <jats:italic>N<\/jats:italic>\u2010demethylated <jats:italic>in vivo<\/jats:italic> to 3\u2010methoxymorphinan by human CYP3A4\/5. The metabolic ratio (MR) of dextromethorphan\/3\u2010methoxymorphinan in plasma, saliva and urinary were examined as a possible <jats:italic>in vivo<\/jats:italic> probe of CYP3A activity. In limited previous studies, 4 h urinary samples were collected for determining the MR. To evaluate the repeatability and validity of previously reported and other potential phenotyping methods, the MR from urine samples (at various intervals), from plasma and from saliva (at varying time points) were determined after repetitive single doses of immediate\u2010release or repetitive multiple doses of controlled\u2010release dextromethorphan preparations. For the single\u2010dose study, each of 12 subjects received 15 mg of immediate\u2010release dextromethorphan in periods II and I, respectively, with a 1 week washout period. For the multiple dose study, each of 16 subjects received 60 mg controlled release dextromethorphan twice daily for 5 days in periods I and II, respectively, with a 2 week washout period. Dextromethorphan and 3\u2010methoxymorphinan are assayed by high\u2010performance liquid chromatography. In the single\u2010dose study, all of the urine MR revealed good repeatabilities for the periods (paired <jats:italic>t<\/jats:italic>\u2010test). The urine MR at any time interval of 0\u20136 h, 0\u20138 h and 0\u201312 h correlated significantly with the MR from 0\u201324 h urine (<jats:italic>r<\/jats:italic>&gt;0.8, <jats:italic>p<\/jats:italic>&lt;0.05). In the multiple\u2010dose study, all MR revealed good repeatabilities for the two periods (paired <jats:italic>t<\/jats:italic>\u2010test). The plasma MR at any time between 0.5 h and 12 h, the saliva MR at 12 h and the urine MR at any interval between 0\u20132 h, 0\u20134 h, 0\u20136 h, 0\u20138 h, 0\u201312 h and 0\u201324 h could predict the MR from AUC<jats:sub>\u03c4<\/jats:sub><jats:sup>ss<\/jats:sup>. In conclusion, the urine sample as 0\u20136 h, 0\u20138 h or 0\u201312 h in the single immediate\u2010release dose (15 mg) or in the multiple controlled\u2010release dose (60 mg) procedure, the saliva sample at 12 h, the urine sample at 0\u20132 h, 0\u20134 h, 0\u20136 h, 0\u20138 h, 0\u201312 h, 0\u201324 h or all plasma\u2010sampling points 0.5\u201312 h could be used as the dextromethorphan MR for determining the CYP3A activity. Copyright \u00a9 2003 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.373","type":"journal-article","created":{"date-parts":[[2003,12,17]],"date-time":"2003-12-17T08:00:51Z","timestamp":1071648051000},"page":"367-373","source":"Crossref","is-referenced-by-count":5,"title":["Single\u2010point plasma or urine dextromethorphan method for determining CYP3A activity"],"prefix":"10.1002","volume":"24","author":[{"given":"Benjamin Pei\u2010Chung","family":"Kuo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver Yoa\u2010Pu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Huei","family":"Hsiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Heng","family":"Pao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting\u2010Shien","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi\u2010Feng","family":"Hung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,9,25]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00073.x"},{"key":"e_1_2_1_3_2","first-page":"549","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_1_4_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408449209145319"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199408000-00001"},{"key":"e_1_2_1_6_2","first-page":"557","article-title":"Use of midazolam as a human cytochrome P4503A probe; II: characterization of inter\u2010 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_1_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113933"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(95)00431-9"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(94)90237-2"},{"key":"e_1_2_1_10_2","first-page":"955","article-title":"Novel single\u2010point plasma or saliva dextromethorphen method for determining CYP2D6 activity","volume":"285","author":"Hu OYP","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(95)00574-9"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1991.48"}],"container-title":["Biopharmaceutics &amp; Drug Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdd.373","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdd.373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T14:39:52Z","timestamp":1700231992000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdd.373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9,25]]},"references-count":11,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2003,12]]}},"alternative-id":["10.1002\/bdd.373"],"URL":"https:\/\/doi.org\/10.1002\/bdd.373","archive":["Portico"],"relation":{},"ISSN":["0142-2782","1099-081X"],"issn-type":[{"value":"0142-2782","type":"print"},{"value":"1099-081X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9,25]]}}}