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Drug exposure metrics were explored for potential relationships with efficacy and safety end points. Total cariprazine exposures were significantly related to reductions in Positive and Negative Syndrome Scale (PANSS) or Young Mania Rating Scale (YMRS) total scores in schizophrenia or bipolar mania, respectively, via a maximum effect (<jats:italic>E<\/jats:italic><jats:sub>max<\/jats:sub>)\u2010type relationship. Typical steady\u2010state plasma concentrations after 3 and 4.5\u00a0mg\/day were associated with 50% of maximum typical reductions in PANSS and YMRS total scores, respectively. Time\u2010weighted cariprazine exposures had significant relationships with the probability of common adverse events (AEs). Dose increase was associated with increased efficacy but was also associated with an increase in AEs. Results of these pharmacokinetic\/pharmacodynamic analyses support that the recommended dose range (1.5\u20136\u00a0mg\/day for schizophrenia and 3\u20136\u00a0mg\/day for bipolar mania) provides an appropriate benefit\u2010risk balance between cariprazine efficacy and safety.<\/jats:p>","DOI":"10.1111\/cts.12720","type":"journal-article","created":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T15:26:18Z","timestamp":1572449178000},"page":"362-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Relationship Between Plasma Concentrations and Clinical Effects of Cariprazine in Patients With Schizophrenia or Bipolar Mania"],"prefix":"10.1111","volume":"13","author":[{"given":"Antonia","family":"Periclou","sequence":"first","affiliation":[{"name":"Allergan Madison New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Willavize","sequence":"additional","affiliation":[{"name":"Cognigen Corporation Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jaworowicz","sequence":"additional","affiliation":[{"name":"Cognigen Corporation Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Passarell","sequence":"additional","affiliation":[{"name":"Cognigen Corporation Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Carrothers","sequence":"additional","affiliation":[{"name":"Allergan Madison New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parviz","family":"Ghahramani","sequence":"additional","affiliation":[{"name":"Forest Research Institute, Inc., an Allergan affiliate Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Durgam","sequence":"additional","affiliation":[{"name":"Allergan Madison New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willie","family":"Earley","sequence":"additional","affiliation":[{"name":"Allergan Madison New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margit","family":"Kap\u00e1s","sequence":"additional","affiliation":[{"name":"Gedeon Richter Plc Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Khariton","sequence":"additional","affiliation":[{"name":"Forest Research Institute, Inc., an Allergan affiliate Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,27]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2014.1319"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130100711"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.40.1.67"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.129307"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.160432"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S95100"},{"key":"e_1_2_10_7_1","first-page":"140","article-title":"Phase I study of RGH\u2010188 in schizophrenic patients","volume":"11","author":"Ereshefsky L.","year":"2008","journal-title":"Int. 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