{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T23:03:15Z","timestamp":1776294195357,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oxybutynin is a racemic anticholinergic drug used for the symptomatic treatment of detrusor overactivity. The formation of active metabolites related to tolerability problems depends on the route of administration. The objective of this evaluation was to develop a pharmacokinetic model for oral\/intravesical administration as the basis for simulations with different dosages. Data from a published changeover clinical study with 18 healthy adults receiving a single oral dose of 5\u00a0mg immediate\u2010release oxybutynin and single and multiple intravesical doses of 10\u00a0mg oxybutynin solution was evaluated. Enantioselective plasma concentrations of oxybutynin and N\u2010desethyloxybutynin (NDO) were used to establish a population pharmacokinetic model using nonlinear mixed\u2010effects modeling with NONMEM 7.4.1. For both enantiomers, the data were described well by a 2\u2010compartment model for oxybutynin with an additional compartment for NDO. Oxybutynin absorption was modeled by transit compartments for oral and first\u2010order absorption for intravesical application. Bioavailability of the more active (R)\u2010enantiomer was 7% for oral and 10%\u201022% for intravesical administration. In simulations, intravesical doses of 5 to 15\u00a0mg (R)\u2010oxybutynin administered 2 to 3 times daily decreased peak\u2010trough fluctuations of NDO to 8% compared with 24% after oral administration. The NDO\/oxybutynin ratio was reduced from 17 after oral administration to unity. Chronic intravesical versus oral administration of (R)\u2010oxybutynin generates distinctly lower and less variable concentrations of (R)\u2010NDO. Pharmacokinetic simulations suggest that exposure for 12.5\u00a0mg (R)\u2010oxybutynin administered twice daily might not compromise efficacy and tolerability compared with exposure for standard thrice\u2010daily administrations. This assumption needs to be assessed in clinical studies.<\/jats:p>","DOI":"10.1002\/jcph.1809","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T12:39:09Z","timestamp":1609159149000},"page":"961-971","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Population Pharmacokinetic Model of (R)\u2010 and (S\u2010) Oxybutynin and Its Active Metabolites After Oral and Intravesical Administration to Healthy Volunteers"],"prefix":"10.1002","volume":"61","author":[{"given":"Melanie","family":"Kretschmar","sequence":"first","affiliation":[{"name":"Department I of Pharmacology University of Cologne Faculty of Medicine and University Hospital Cologne Center for Pharmacology  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed Abbas","family":"Suleiman","sequence":"additional","affiliation":[{"name":"Department I of Pharmacology University of Cologne Faculty of Medicine and University Hospital Cologne Center for Pharmacology  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Krause","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery University of Cologne Faculty of Medicine and University Hospital Cologne Heart Center  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Mediconomics GmbH  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raimund","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Pediatric Adolescent and Reconstructive Urology Medical Faculty Mannheim University Medical Center Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Rubenwolf","sequence":"additional","affiliation":[{"name":"Department of Urology Frankfurt University Medical Center Johann Wolfgang Goethe\u2010University  Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Fuhr","sequence":"additional","affiliation":[{"name":"Department I of Pharmacology University of Cologne Faculty of Medicine and University Hospital Cologne Center for Pharmacology  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Taubert","sequence":"additional","affiliation":[{"name":"Department I of Pharmacology University of Cologne Faculty of Medicine and University Hospital Cologne Center for Pharmacology  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(99)00498-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)62828-3"},{"issue":"3","key":"e_1_2_10_4_1","first-page":"687","article-title":"Guidelines on neurogenic lower urinary tract dysfunction","volume":"17","author":"St\u00f6hrer M","year":"2007","journal-title":"Prog Urol"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(03)00622-7"},{"issue":"2","key":"e_1_2_10_6_1","first-page":"562","article-title":"Enantiomers of oxybutynin: in vitro pharmacological characterization at M1, M2 and M3 muscarinic receptors and in vivo effects on urinary bladder contraction, mydriasis and salivary secretion in guinea pigs","volume":"256","author":"Noronha\u2010Blob L","year":"1991","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702551"},{"issue":"10","key":"e_1_2_10_8_1","first-page":"1012","article-title":"Comparison of the antimuscarinic and antispasmodic actions of racemic oxybutynin and desethyloxybutynin and their enantiomers with those of racemic terodiline","volume":"48","author":"Smith ER","year":"1998","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00558247"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bms.1200081009"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199810000-00010"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1998.tb01418.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-005-0012-8"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0306-5251.2001.01463.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/009127009903900313"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/003655902317259319"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.05.011"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6777(1997)16:6<533::AID-NAU3>3.0.CO;2-F"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2014.10.018"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(00)88316-2"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(99)90089-9"},{"issue":"1","key":"e_1_2_10_22_1","first-page":"12","article-title":"A comparative review of oxybutynin chloride formulations: pharmacokinetics and therapeutic efficacy in overactive bladder","volume":"12","author":"Kennelly MJ","year":"2010","journal-title":"Rev Urol"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2010.02626.x"},{"key":"e_1_2_10_24_1","first-page":"S26","article-title":"Transdermal systems for overactive bladder: principles and practice","volume":"5","author":"Staskin DR","year":"2003","journal-title":"Rev Urol"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)66095-8"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3100995"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000019701"},{"key":"e_1_2_10_28_1","volume-title":"NONMEM User's Guides (1989\u20102009)","author":"Beal S","year":"2009"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.24"},{"key":"e_1_2_10_30_1","unstructured":"R Core Team.R: a language and environment for statistical computing. Vienna Austria: R Foundation for Statistical Computing.http:\/\/www.R-project.org\/. Published 2013. Accessed July 22 2018."},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270002250613"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-007-9066-0"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.14"},{"issue":"9","key":"e_1_2_10_34_1","first-page":"128","article-title":"NONMEM users guide: introduction to NONMEM 7.2.0","volume":"53","author":"Bauer RJ","year":"2011","journal-title":"J Chem Inf Model"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9112-5"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01113502"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199630050-00001"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2017.1342288"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.1.341"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498259209053145"},{"key":"e_1_2_10_41_1","unstructured":"Sanofi Aventis Deutschland GmbH. Fachinformation Dridase \u00ae.https:\/\/www.gelbe-liste.de\/produkte\/Dridase-5-mg-Tabletten_13102\/fachinformation. Published 2015. Accessed October 12 2017."},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.008672"},{"issue":"3","key":"e_1_2_10_43_1","first-page":"1552","article-title":"Characterization of interintestinal and intraintestinal variations in human CYP3A\u2010dependent metabolism","volume":"283","author":"Paine MF","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0351-6"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-016-9965-3"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5173(96)04592-9"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5173(99)00147-7"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-409X(96)00009-9"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)36663-6"},{"issue":"2","key":"e_1_2_10_50_1","first-page":"84","article-title":"Control of detrusor hyperreflexia by the intravesical instillation of oxybutynine hydrochloride","volume":"29","author":"Madersbacher H","year":"1991","journal-title":"Paraplegia"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(01)00497-2"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498250600976088"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010956832113"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.4065\/78.6.696"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1809","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.1809","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1809","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T22:49:29Z","timestamp":1693349369000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,13]]},"references-count":53,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/jcph.1809"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1809","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,13]]},"assertion":[{"value":"2020-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}