{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:09:12Z","timestamp":1792440552395,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":189,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:p><jats:bold>Study Objective.<\/jats:bold> To compare the effects of paroxetine on the pharmacokinetics and pharmacodynamics of the immediate\u2010release (IR) and extended\u2010release (ER) formulations of metoprolol.<\/jats:p><jats:p><jats:bold>Design.<\/jats:bold> Prospective, randomized, open\u2010label, 3\u2010way crossover study.<\/jats:p><jats:p><jats:bold>Setting.<\/jats:bold> General clinical research center.<\/jats:p><jats:p><jats:bold>Subjects.<\/jats:bold> Fifteen healthy volunteers with at least one active cytochrome P450 (CYP) <jats:italic>CYP2D6<\/jats:italic> allele (<jats:italic>CYP2D6*1<\/jats:italic> or <jats:italic>CYP2D6*2<\/jats:italic>).<\/jats:p><jats:p><jats:bold>Intervention.<\/jats:bold> In each of three phases conducted in random sequence, subjects received one of three metoprolol formulations administered on day 1: a single dose of metoprolol ER 100 mg, a single dose of metoprolol ER 200 mg, or two 100\u2010mg doses of metoprolol IR administered 12 hours apart. Oral paroxetine 20 mg\/day was then given alone on days 2\u20137 and coadministered with the same metoprolol formulation on day 8. Subjects received each of the other two formulations during the next two phases, with a 14\u2010day washout period between each phase.<\/jats:p><jats:p><jats:bold>Measurements and Main Results.<\/jats:bold> After receiving metoprolol on days 1 (before paroxetine) and 8 (after paroxetine), S\u2010 and R\u2010metoprolol pharmacokinetic parameters and exercise heart rate and blood pressure responses were measured. The mean area under the plasma concentration\u2010time curve values of both S\u2010 and R\u2010metoprolol for each formulation were increased approximately 3\u2010 and 4\u2010fold, respectively, by paroxetine. Paroxetine significantly increased the S\u2010 and R\u2010metoprolol maximum concentration (C<jats:sub>max<\/jats:sub>) of each formulation and increased the elimination half\u2010life of both isomers approximately 2\u2010fold. When metoprolol IR was given with paroxetine, the S\u2010metoprolol C<jats:sub>max<\/jats:sub> was significantly greater than that of either the 100\u2010mg or 200\u2010mg ER products. The maximum effect of metoprolol IR on heart rate was significantly greater than that of metoprolol ER 200 mg, independent of whether the agents were administered alone or with paroxetine. Both the heart rate and systolic blood pressure area under the effect\u2010time curve values were significantly decreased by paroxetine.<\/jats:p><jats:p><jats:bold>Conclusion.<\/jats:bold> Paroxetine significantly inhibits the metabolism of both metoprolol IR and ER, resulting in an increase in the magnitude and duration of \u03b2\u2010blockade. The potential risk of adverse effects from excessive \u03b2\u2010blockade may be greater with metoprolol IR than with metoprolol ER because of the significantly higher peak S\u2010metoprolol plasma concentrations achieved with the IR formulation. Thus, if paroxetine treatment is indicated in patients receiving metoprolol, use of the ER formulation may reduce the risk of adverse effects.<\/jats:p>","DOI":"10.1592\/phco.31.7.630","type":"journal-article","created":{"date-parts":[[2011,6,25]],"date-time":"2011-06-25T15:22:01Z","timestamp":1309015321000},"page":"630-641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Effects of Paroxetine on the Pharmacokinetics and Pharmacodynamics of Immediate\u2010Release and Extended\u2010Release Metoprolol"],"prefix":"10.1002","volume":"31","author":[{"given":"Robert B.","family":"Parker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith E.","family":"Soberman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1983.242"},{"key":"e_1_2_1_3_2","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S0090-9556(25)07354-4","article-title":"Metoprolol metabolism via cytochrome P4502D6 in ethnic populations","volume":"24","author":"Johnson JA","year":"1996","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.2165\/11318030-000000000-00000"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198212163072505"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200208000-00007"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.106464"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.081109"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.psy.0000126207.43307.c0"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.06.055"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.168.20.2232"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.851675"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.6.701"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.03.068"},{"key":"e_1_2_1_15_2","first-page":"656","article-title":"Metoprolol\u2010paroxetine interaction in human liver microsomes: stereoselective aspects and prediction of the in vivo interaction","volume":"29","author":"Hemeryck A.","year":"2001","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.104788"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1990.tb03491.x"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1990.tb03493.x"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200302000-00001"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91265-N"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1207\/s15327752jpa6703_13"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1985.tb05112.x"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(91)80325-7"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2004.05.029"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-008-0504-8"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00316471"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1989.tb05391.x"},{"key":"e_1_2_1_28_2","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S0022-3565(25)23095-6","article-title":"Debrisoquine phenotype and the pharmacokinetics and \u03b22\u2010receptor pharmacodynamics of metoprolol and its enantiomers","volume":"256","author":"Jonkers RE","year":"1991","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-007-0404-3"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1990.tb03490.x"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.26.9.1247"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13842-1"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00578406"},{"key":"e_1_2_1_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.190769"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.30.3.304"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1177\/009127000004000108"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-200204000-00010"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.172"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.218"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.127111"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2005.07.004"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.08.020"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.07.002"},{"key":"e_1_2_1_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1990.tb03495.x"},{"key":"e_1_2_1_45_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.27.6.874"},{"key":"e_1_2_1_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00224-8"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.tpj.6500354"},{"key":"e_1_2_1_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(02)17734-4"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1592%2Fphco.31.7.630","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1592\/phco.31.7.630","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T16:10:34Z","timestamp":1761063034000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1592\/phco.31.7.630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,7]]},"references-count":47,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2011,7]]}},"alternative-id":["10.1592\/phco.31.7.630"],"URL":"https:\/\/doi.org\/10.1592\/phco.31.7.630","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,7]]},"assertion":[{"value":"2012-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}