{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:55:07Z","timestamp":1791111307063,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,7,11]],"date-time":"2011-07-11T00:00:00Z","timestamp":1310342400000},"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":[[2011,8]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Tolterodine and 5\u2010hydroxymethyl tolterodine (5\u2010HMT) are equipotent active moieties of tolterodine; 5\u2010HMT is the singular active moiety of fesoterodine. The formation of 5\u2010HMT from tolterodine occurs via CYP2D6, and some subjects are poor metabolizers CYP2D6. On the other hand, the formation of 5\u2010HMT from fesoterodine occurs via ubiquitous esterases. Cross\u2010study comparisons of data from phase 1 studies suggest that active moiety exposures are considerably more variable following tolterodine extended release <jats:italic>vs.<\/jats:italic> fesoterodine.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003This head\u2010to\u2010head study confirmed the findings of reduced pharmacokinetic variability of fesoterodine and further delineates that tolterodine, and not 5\u2010HMT, was the principal source of variability after administration of tolterodine extended release. The data suggest that fesoterodine delivers 5\u2010HMT consistently, regardless of CYP2D6 status, with up to 40% higher bioavailability compared with tolterodine.<\/jats:p><jats:p><jats:bold>AIMS<\/jats:bold> Tolterodine and 5\u2010hydroxymethyl tolterodine (5\u2010HMT) are equipotent active moieties of tolterodine; 5\u2010HMT is the singular active moiety of fesoterodine. Formation of 5\u2010HMT from fesoterodine and tolterodine occurs via esterases and CYP2D6 respectively. This randomized, crossover, open\u2010label, multiple\u2010dose study in CYP2D6 extensive metabolizers (EMs) and poor metabolizers (PMs) compared the pharmacokinetics of fesoterodine <jats:italic>vs.<\/jats:italic> tolterodine extended release (ER).<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold> Subjects received fesoterodine and tolterodine ER with a \u22653\u2010day washout period. Treatment comprised 4\u2010mg once daily doses for 5 days escalated to 8\u2010mg once daily for 5 days. Pharmacokinetics of active moieties were compared by drug, dose and genotype.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold> Active moiety exposures following fesoterodine and tolterodine ER increased proportional to dose in EMs and PMs. In EMs only, coefficients of variation for AUC and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> following fesoterodine (up to 46% and 48% respectively) were lower than those following tolterodine ER (up to 87% and 87% respectively). Following fesoterodine and tolterodine ER administration, active moiety exposures ranged up to sevenfold and 40\u2010fold respectively. Mean urinary excretion of 5\u2010HMT following fesoterodine 4 and 8\u2003mg, respectively, was 0.44 and 0.89\u2003mg in EMs and 0.60 and 1.32\u2003mg in PMs. Following tolterodine ER 4 and 8\u2003mg, it was 0.38 and 0.71\u2003mg respectively (EMs only). Renal clearance was similar regardless of administered drug, dose or genotype.<\/jats:p><jats:p><jats:bold>CONCLUSIONS<\/jats:bold> Tolterodine, not 5\u2010HMT, was the principal source of variability after tolterodine ER administration. Fesoterodine delivers 5\u2010HMT with less variability than tolterodine, regardless of CYP2D6 status, with up to 40% higher bioavailability. The pharmacokinetics of fesoterodine were considerably less variable than TER.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2011.03948.x","type":"journal-article","created":{"date-parts":[[2011,2,26]],"date-time":"2011-02-26T15:56:03Z","timestamp":1298735763000},"page":"226-234","source":"Crossref","is-referenced-by-count":20,"title":["Comparison of pharmacokinetic variability of fesoterodine <i>vs.<\/i> tolterodine extended release in cytochrome P450 2D6 extensive and poor metabolizers"],"prefix":"10.1111","volume":"72","author":[{"given":"Bimal","family":"Malhotra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edress","family":"Darsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope","family":"Crownover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanzhi","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Glue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,7,11]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOU.0b013e32832ce8a4"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2008.06.047"},{"key":"e_1_2_7_4_2","first-page":"13","article-title":"The mechanism of action of tolterodine","volume":"11","author":"Nilvebrant L","year":"2000","journal-title":"Rev Contemp Pharmacother"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euus.2004.09.001"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1358\/dof.2004.029.07.854168"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-003-0832-2"},{"key":"e_1_2_7_8_2","volume-title":"Toviaz (fesoterodine). 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