{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:44:41Z","timestamp":1783435481845,"version":"3.54.6"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,8,18]],"date-time":"2012-08-18T00:00:00Z","timestamp":1345248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The inhibition potencies of aripiprazole and its active metabolite, dehydroaripiprazole, on the activities of human multidrug resistance protein 1 (MDR1\/ABCB1; P\u2010glycoprotein), breast cancer resistance protein (BCRP\/ABCG2) and multidrug resistance\u2010associated protein 4 (MRP4\/ABCC4), that are drug efflux transporters expressed both in the intestine and at the blood\u2013brain barrier (BBB), were investigated. Aripiprazole and dehydroapripiprazole showed relatively strong inhibitory effects on human MDR1 with IC<jats:sub>50<\/jats:sub>values of 1.2 and 1.3\u2009\u00b5<jats:sc>m<\/jats:sc>in human MDR1\u2010transfected Mardin\u2010Darby canine kidney (MDCKII\u2010MDR1) cells, respectively. The inhibition potencies of other atypical antipsychotics (risperidone, paliperidone, olanzapine and ziprasidone) for human MDR1 were also evaluated using the same<jats:italic>in vitro<\/jats:italic>experimental system and IC<jats:sub>50<\/jats:sub>values were more than 10\u2010fold higher than those of the two compounds. Aripiprazole and dehydroaripiprazole also had inhibition potencies against human BCRP with IC<jats:sub>50<\/jats:sub>values of 3.5 and 0.52\u2009\u00b5<jats:sc>m<\/jats:sc>, respectively. The ratios of steady\u2010state unbound concentrations of aripiprazole and dehydroaripiprazole to their IC<jats:sub>50<\/jats:sub>values against human MDR1 and BCRP activities were less than 0.1, whereas the theoretically maximum gastrointestinal concentration of aripiprazole ([<jats:italic>I<\/jats:italic>]<jats:sub>2<\/jats:sub>) to its IC<jats:sub>50<\/jats:sub>values was much higher than the cut\u2010off value of 10, proposed by the International Transporter Consortium (ITC) and the Food and Drug Administration (FDA). In contrast, aripiprazole and dehydroaripiprazole showed almost no inhibitory effect against the activity of human MRP4. These findings indicate that aripiprazole is unlikely to cause drug\u2013drug interactions (DDIs) at the BBB when co\u2010administered with substrate drugs of these drug transporters investigated. However, interactions at the intestinal absorption process may be of concern. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.1801","type":"journal-article","created":{"date-parts":[[2012,7,28]],"date-time":"2012-07-28T09:01:03Z","timestamp":1343466063000},"page":"304-315","source":"Crossref","is-referenced-by-count":23,"title":["Effects of aripiprazole and its active metabolite dehydroaripiprazole on the activities of drug efflux transporters expressed both in the intestine and at the blood\u2013brain barrier"],"prefix":"10.1002","volume":"33","author":[{"given":"Yasuhisa","family":"Nagasaka","sequence":"first","affiliation":[{"name":"Drug Metabolism Research Laboratories Astellas Pharma Inc. 1\u20106 Kashima, 2\u2010chome Yodogawa\u2010ku Osaka 532\u20108514 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Oda","sequence":"additional","affiliation":[{"name":"Drug Metabolism Research Laboratories Astellas Pharma Inc. 1\u20106 Kashima, 2\u2010chome Yodogawa\u2010ku Osaka 532\u20108514 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Iwatsubo","sequence":"additional","affiliation":[{"name":"Drug Metabolism Research Laboratories Astellas Pharma Inc. 1\u20106 Kashima, 2\u2010chome Yodogawa\u2010ku Osaka 532\u20108514 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Drug Metabolism Research Laboratories Astellas Pharma Inc. 1\u20106 Kashima, 2\u2010chome Yodogawa\u2010ku Osaka 532\u20108514 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Usui","sequence":"additional","affiliation":[{"name":"Drug Metabolism Research Laboratories Astellas Pharma Inc. 1\u20106 Kashima, 2\u2010chome Yodogawa\u2010ku Osaka 532\u20108514 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3028"},{"key":"e_1_2_8_3_1","unstructured":"US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER). 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