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Ketoconazole increased the maximumplasma concentration (Cmax) and area under the plasma concentration vs time curve to infinity (AUC\u29dd of fimasartan by 2.47\u2010fold (90% confidence interval [CI], 1.61\u20103.79) and 2.03\u2010fold (1.56\u20102.64), respectively. Concomitant administration of rifampicin increased the C<jats:sub>max<\/jats:sub> and AUC\u221e of fimasartan by 10.33\u2010fold (90% CI, 6.74\u201015.81) and 4.60\u2010fold (3.54\u20105.97). In vitro studies indicated that ketoconazole inhibited the uptake of fimasartan into cells expressing OATP1B1 with a K<jats:italic><jats:sub>i<\/jats:sub><\/jats:italic> of 107.7 \u00b5M, and rifampicin inhibited OAT1\u2010 and OATP1B1\u2010mediated fimasartan transport with a K<jats:italic><jats:sub>i<\/jats:sub><\/jats:italic> of 212 \u00b5M and 12.2 \u00b5M, respectively. The systemic exposure of fimasartan was significantly increased by coadministration of ketoconazole or rifampicin in healthy volunteers. This is consistent with the in vitro results, in which fimasartan is a substrate of CYP3A and OATP1B1.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0091270011433328","type":"journal-article","created":{"date-parts":[[2012,1,27]],"date-time":"2012-01-27T03:58:00Z","timestamp":1327636680000},"page":"75-81","source":"Crossref","is-referenced-by-count":25,"title":["Increased Systemic Exposure of Fimasartan, an Angiotensin II Receptor Antagonist, by Ketoconazole and Rifampicin"],"prefix":"10.1002","volume":"53","author":[{"given":"Jung Won","family":"Kim","sequence":"first","affiliation":[{"name":"Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SoJeong","family":"Yi","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae\u2010Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoung Soo","family":"Lim","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seo Hyun","family":"Yoon","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joo\u2010Youn","family":"Cho","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Goo","family":"Lee","sequence":"additional","affiliation":[{"name":"Yonsei University College of Medicine  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Im\u2010Sook","family":"Song","sequence":"additional","affiliation":[{"name":"Inje University College of Medicine  Busan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang\u2010Goo","family":"Shin","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u2010Jin","family":"Jang","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung\u2010Sang","family":"Yu","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,6,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e31821795d0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e31822b9092"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.5414\/CP201533"},{"key":"e_1_2_8_5_1","article-title":"Single dose pharmacokinetics (PK) and pharmacodynamics (PD) of BR\u2010A\u2010657, an angiotensin II (AII) antagonist","volume":"77","author":"Lane A","year":"2005","journal-title":"Clin Pharmacol Ther"},{"key":"e_1_2_8_6_1","article-title":"Multiple dose pharmacokinetics (PK) and pharmacodynamics (PD) of BR\u2010A\u2010657, an angiotensin II (AII) antagonist","volume":"77","author":"Lane A","year":"2005","journal-title":"Clin Pharmacol Ther"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(98)90172-2"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008325931"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.749"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.108282"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fpc.0000215070.52212.0e"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100075"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-004-0746-z"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007299928"},{"key":"e_1_2_8_15_1","unstructured":"Food and Drug Administration (FDA).Guidance for Industry: Drug Interaction Studies\u2014Study Design Data Analysis and Implications for Dosing and Labeling. 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