{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T22:49:03Z","timestamp":1772750943808,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,8,9]],"date-time":"2018-08-09T00:00:00Z","timestamp":1533772800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Daiichi Sankyo, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The primary aim of this study was to assess the individual effects of probenecid and cimetidine on mirogabalin exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This phase 1, open\u2010label, crossover study randomized healthy adults to receive three treatment regimens, each separated by \u22655\u2010day washout: a single oral dose of mirogabalin 15\u00a0mg on day 2, mirogabalin 15\u00a0mg on day 2 plus probenecid 500\u00a0mg every 6\u00a0h from days 1 to 4, and mirogabalin 15\u00a0mg on day 2 plus cimetidine 400\u00a0mg every 6\u00a0h from days 1 to 4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Coadministration of mirogabalin with probenecid or cimetidine increased the maximum and total mirogabalin exposure. The geometric mean ratios of C<jats:sub>max<\/jats:sub> and AUC<jats:sub>(0\u2010t)<\/jats:sub> (90% CI) with and without coadministration of probenecid were 128.7% (121.9\u2013135.7%) and 176.1% (171.9\u2013180.3%), respectively. The geometric mean ratios of C<jats:sub>max<\/jats:sub> and AUC<jats:sub>(0\u2010t)<\/jats:sub> (90% CI) with and without coadministration of cimetidine were 117.1% (111.0\u2013123.6%) and 143.7% (140.3\u2013147.2%), respectively. Mean (standard deviation) renal clearance of mirogabalin (l\u00a0h<jats:sup>\u20131<\/jats:sup>) was substantially slower after probenecid [6.67 (1.53)] or cimetidine [7.17 (1.68)] coadministration, compared with mirogabalin alone [11.3 (2.39)]. Coadministration of probenecid or cimetidine decreased mirogabalin mean (standard deviation) apparent total body clearance [10.5 (2.33) and 12.8 (2.67) l\u00a0h<jats:sup>\u20131<\/jats:sup>, respectively, <jats:italic>vs<\/jats:italic>. 18.4 (3.93) for mirogabalin alone].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A greater magnitude of change in mirogabalin exposure was observed when coadministered with a drug that inhibits both renal and metabolic clearance (probenecid) <jats:italic>vs<\/jats:italic>. a drug that only affects renal clearance (cimetidine). However, as the increase in exposure is not clinically significant (&gt;2\u2010fold), no <jats:italic>a priori<\/jats:italic> dose adjustment is recommended.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13674","type":"journal-article","created":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T19:03:38Z","timestamp":1529435018000},"page":"2317-2324","source":"Crossref","is-referenced-by-count":15,"title":["Coadministration of probenecid and cimetidine with mirogabalin in healthy subjects: A phase 1, randomized, open\u2010label, drug\u2013drug interaction study"],"prefix":"10.1111","volume":"84","author":[{"given":"Masaya","family":"Tachibana","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naotoshi","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Pharmacokinetics Research Laboratories Daiichi Sankyo Co., Ltd.  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Basking Ridge NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-5669","authenticated-orcid":false,"given":"Hamim","family":"Zahir","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Inc.  Basking Ridge NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000259085.61898.9e"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4637.2007.00347.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/JMDH.S106340"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0356-09.2009"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a003947"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1044"},{"key":"e_1_2_10_8_1","unstructured":"FDA Guidance for Industry.Drug Interaction Studies \u2014 Study Design Data Analysis Implications for Dosing and Labeling Recommendations 2012. 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