{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:52:57Z","timestamp":1783075977754,"version":"3.54.6"},"reference-count":38,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2011,12,21]],"date-time":"2011-12-21T00:00:00Z","timestamp":1324425600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p>\n                    Positron emission tomography (PET) studies of dopamine receptor occupancy can be used to assess dosing of antipsychotics. Typically, studies of antipsychotics have applied pharmacodynamic (PD) modeling alone to characterize the relationship between antipsychotic dose and its effect on the brain. However, a limitation of this approach is that it does not account for the discrepancy between the time courses of plasma concentration and receptor occupancy by antipsychotics. Combined pharmacokinetic\u2014PD (PK\u2014PD) modeling, by incorporating the time dependence of occupancy, is better suited for the reliable analysis of the concentration\u2014occupancy relationship. To determine the effect of time on the concentration\u2014occupancy relationship as a function of analysis approach, we measured dopamine receptor occupancy after the administration of aripiprazole using [\n                    <jats:sup>11<\/jats:sup>\n                    C]raclopride PET and obtained serial measurements of the plasma aripiprazole concentration in 18 volunteers. We then developed a PK\u2014PD model for the relationship, and compared it with conventional approach (PD modeling alone). The hysteresis characteristics were observed in the competitor concentration\u2014occupancy relationship and the value of EC\n                    <jats:sub>50<\/jats:sub>\n                    was different according to the analysis approach ( EC\n                    <jats:sub>50<\/jats:sub>\n                    derived from PD modeling alone = 11.1 ng\/mL (95% confidence interval (CI) = 10.1 to 12.1); while that derived from combined PK\u2014PD modeling = 8.63 ng\/mL (95% CI = 7.75 to 9.51)). This finding suggests that PK\u2014PD modeling is required to obtain reliable prediction of brain occupancy by antipsychotics.\n                  <\/jats:p>","DOI":"10.1038\/jcbfm.2011.180","type":"journal-article","created":{"date-parts":[[2011,12,21]],"date-time":"2011-12-21T06:00:46Z","timestamp":1324447246000},"page":"759-768","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":27,"title":["Predicting Brain Occupancy from Plasma Levels using PET: Superiority of Combining Pharmacokinetics with Pharmacodynamics while Modeling the Relationship"],"prefix":"10.1177","volume":"32","author":[{"given":"Euitae","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea"},{"name":"Psychiatric Imaging, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London, UK"},{"name":"King's College London, Institute of Psychiatry, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver D","family":"Howes","sequence":"additional","affiliation":[{"name":"Psychiatric Imaging, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London, UK"},{"name":"King's College London, Institute of Psychiatry, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Hyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Min","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Sung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Jin","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Goo","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico E","family":"Turkheimer","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shitij","family":"Kapur","sequence":"additional","affiliation":[{"name":"King's College London, Institute of Psychiatry, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Soo","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea"},{"name":"Brain and Cognitive Science-WCU Program, Seoul National University College of Natural Sciences, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,12,21]]},"reference":[{"key":"bibr1-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.175"},{"key":"bibr2-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199936050-00005"},{"key":"bibr3-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-004-1826-6"},{"key":"bibr4-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.2174\/1567201043334542"},{"key":"bibr5-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-010-9247-4"},{"key":"bibr6-jcbfm.2011.180","volume-title":"Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition (SCID-I\/NP).","author":"First MB","year":"2002"},{"key":"bibr7-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241080-00003"},{"key":"bibr8-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2008.07101574"},{"key":"bibr9-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198106060-00002"},{"key":"bibr10-jcbfm.2011.180","first-page":"273","volume":"5","author":"Holford NH","year":"1981","journal-title":"Crit Rev Bioeng"},{"key":"bibr11-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.2174\/138161209788957528"},{"key":"bibr12-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199809000-00003"},{"key":"bibr13-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.035303"},{"key":"bibr14-jcbfm.2011.180","first-page":"161","volume":"25","author":"Kapur S","year":"2000","journal-title":"J Psychiatry Neurosci"},{"key":"bibr15-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.157.4.514"},{"key":"bibr16-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2008.33"},{"key":"bibr17-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03223.x"},{"key":"bibr18-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2010.06.010"},{"key":"bibr19-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1996.0066"},{"key":"bibr20-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100049"},{"key":"bibr21-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2010.06.016"},{"key":"bibr22-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.161.5.818"},{"key":"bibr23-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.11.005"},{"key":"bibr24-jcbfm.2011.180","first-page":"401","volume":"35","author":"Meibohm B","year":"1997","journal-title":"Int J Clin Pharmacol Ther"},{"key":"bibr25-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2010.05.037"},{"key":"bibr26-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0879"},{"key":"bibr27-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20771"},{"key":"bibr28-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(04)03334-3"},{"key":"bibr29-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1016\/j.mpaic.2008.06.002"},{"key":"bibr30-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.3.396"},{"key":"bibr31-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.2165\/11316870-000000000-00000"},{"key":"bibr32-jcbfm.2011.180","first-page":"70","volume":"46","author":"Schmidt KC","year":"2002","journal-title":"Q J Nucl Med"},{"key":"bibr33-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023277201179"},{"key":"bibr34-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1126\/science.1145194"},{"key":"bibr35-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1979253358"},{"key":"bibr36-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001009"},{"key":"bibr37-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0b013e31818ba2f6"},{"key":"bibr38-jcbfm.2011.180","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2290"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/jcbfm.2011.180","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1038\/jcbfm.2011.180","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/jcbfm.2011.180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:10:09Z","timestamp":1777493409000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1038\/jcbfm.2011.180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,21]]},"references-count":38,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,4]]}},"alternative-id":["10.1038\/jcbfm.2011.180"],"URL":"https:\/\/doi.org\/10.1038\/jcbfm.2011.180","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,21]]}}}