{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:53:49Z","timestamp":1789610029009,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study assessed the safety, tolerability, and pharmacokinetics of single and multiple oral doses of DA\u20108010, a muscarinic M<jats:sub>3<\/jats:sub> receptor antagonist, in healthy subjects. This was a randomized, double\u2010blind, placebo\u2010controlled, ascending single (Part A: 1, 2.5, 5, 20, and 40\u2009mg QD fasted and 10\u00a0mg QD fasted and fed) and multiple doses (Part B: 5, 10, and 20\u2009mg QD from Days 1 to 7 fasted), sequential\u2010group study. Safety data were analyzed descriptively, time to maximum plasma concentration (<jats:italic>t<\/jats:italic><jats:sub>max<\/jats:sub>) nonparametrically, and pharmacokinetic parameters using power and mixed models and ANOVA. Of 109 subjects randomized (Part A\u00a0=\u00a069 and Part B\u00a0=\u00a040; each part consisted a female group), 31 (44.9%) in Part A and 29 (72.5%) in Part B experienced treatment\u2010emergent adverse events (TEAEs) in a dose\u2010related manner. Common drug\u2010related TEAEs in Part A and B were dizziness (8.7% and 15.0%), headache (5.8% and 12.5%) and blurred vision (8.7% and 20%). One male (20\u2009mg) and one female (10\u00a0mg) from Part B discontinued the study due to a confusional state, and nausea and vomiting. Irrespective of sex, DA\u20108010 was steadily absorbed following single and multiple doses in the fasted state with increased systemic exposure in a dose\u2010proportional manner with maximum plasma concentration occurring at a median <jats:italic>t<\/jats:italic><jats:sub>max<\/jats:sub> between 4.0 and 6.0\u00a0h. A high\u2010fat meal increased systemic exposure. DA\u20108010 was safe, well tolerated, and well absorbed at lower doses and moderately tolerated at higher doses without any notable effects of food and sex.<\/jats:p>","DOI":"10.1002\/prp2.1040","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T13:37:40Z","timestamp":1675431460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Safety, tolerability, and pharmacokinetics of single and multiple ascending Oral doses of <scp>DA<\/scp>\u20108010 in healthy subjects: <scp>First\u2010in\u2010human<\/scp> phase I study"],"prefix":"10.1002","volume":"11","author":[{"given":"Dae Young","family":"Lee","sequence":"first","affiliation":[{"name":"Dong\u2010A ST Research Center  Giheung\u2010gu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Jung","family":"Lee","sequence":"additional","affiliation":[{"name":"Dong\u2010A ST Research Center  Giheung\u2010gu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaelim","family":"Ryu","sequence":"additional","affiliation":[{"name":"Dong\u2010A ST Research Center  Giheung\u2010gu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heewon","family":"Lee","sequence":"additional","affiliation":[{"name":"Dong\u2010A ST HQ  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9189-1114","authenticated-orcid":false,"given":"Ashley","family":"Brooks","sequence":"additional","affiliation":[{"name":"Labcorp Drug Development, Clinical Research Unit Limited, Springfield House  West Yorkshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.02.038"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14050409"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2013.08.031"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192-012-1682-6"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706560"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1677-5538.IBJU.2015.0367"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0090-4295(99)00492-6"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.04.010"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2018.11.037"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12894-020-00611-8"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14748"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016718"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-005-0507-3"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2004.01.008"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192-019-04022-8"},{"issue":"2","key":"e_1_2_13_18_1","first-page":"590","article-title":"Comparison of side effects of Solifenacin vs Tolteridine in patients with urinary incontinence","volume":"10","author":"Butt F","year":"2016","journal-title":"Pak J Med Health Sci"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000447205"}],"container-title":["Pharmacology Research &amp; 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