{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T16:16:10Z","timestamp":1781367370117,"version":"3.54.1"},"reference-count":45,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2017,2,8]],"date-time":"2017-02-08T00:00:00Z","timestamp":1486512000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Biochem"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      This study developed a novel high-performance liquid chromatography (HPLC) method for the simultaneous quantification of clozapine and its active metabolite, N-desmethylclozapine, in human plasma and investigated the effects of various factors, including genetic polymorphisms in cytochrome P450 (CYP) 2D6, CYP3A5, ABCB1 and ABCG2, on the steady-state plasma trough concentrations (C\n                      <jats:sub>0<\/jats:sub>\n                      ) of clozapine and N-desmethylclozapine in Japanese patients with schizophrenia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty-five patients had been receiving fixed doses of clozapine for at least four weeks. The CYP2D6 ( CYP2D6*2, CYP2D6*5, CYP2D6*10), CYP3A5 ( CYP3A5*3), ABCB1 (1236C\u2009&gt;\u2009T, 2677G\u2009&gt;\u2009T\/A, 3435C\u2009&gt;\u2009T) and ABCG2 (421\u2009C\u2009&gt;\u2009A) genotypes were identified by polymerase chain reaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The within- and between-day coefficients of variation (CV) were less than 11.0%, and accuracy was within 9.0% over the linear range from 10 to 2500\u2009ng\/mL for both analytes, and their LOQs were each 10\u2009ng\/mL. The median C\n                      <jats:sub>0<\/jats:sub>\n                      \/dose (C\n                      <jats:sub>0<\/jats:sub>\n                      \/D) ratios of clozapine were significantly higher in patients with the ABCG2 421\u2009A allele than in those with the 421\u2009C\/C genotype ( P\u2009=\u20090.010). However, there were no significant differences in C\n                      <jats:sub>0<\/jats:sub>\n                      \/D ratios of clozapine and N-desmethylclozapine among ABCB1, CYP2D6 or CYP3A5 genotypes. In multiple regression analysis, including polymorphisms, age, body weight and biochemical data of patients, the ABCG2 polymorphism alone was correlated with the C\n                      <jats:sub>0<\/jats:sub>\n                      \/D ratios of clozapine ( R\n                      <jats:sup>2\u2009<\/jats:sup>\n                      =\u20090.139, P\u2009=\u20090.016).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among the various CYPs and drug transporters, BCRP appeared to most strongly influence clozapine exposure. Knowledge of the patient\u2019s ABCG2 421\u2009C\u2009&gt;\u2009A genotype before initiating therapy may be useful when making dosing decisions aimed at achieving optimal clozapine exposure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0004563216686377","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T21:47:09Z","timestamp":1481233629000},"page":"677-685","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":31,"title":["Quantification of the steady-state plasma concentrations of clozapine and N-desmethylclozapine in Japanese patients with schizophrenia using a novel HPLC method and the effects of CYPs and ABC transporters polymorphisms"],"prefix":"10.1177","volume":"54","author":[{"given":"Yumiko","family":"Akamine","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Akita University Hospital, Akita, 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