@article{oai:az.repo.nii.ac.jp:00004662,
 author = {岩橋, 和彦 and 吉原, 英児 and 高田, 直子 and Iwahashi, Kazuhiko and Yoshihara, Eiji and Takada, Naoko},
 journal = {麻布大学雑誌, Journal of Azabu University},
 month = {Mar},
 note = {Neuroleptics Olanzapine is conjugated and oxidized mainly by CYP1A2/CYP2D6. Human CYP1A2 in the 5'-flanking region and intron nucleotide sequence alalysis revealed the existence of a point mutation (-3858) from guanine (wild type; wt) to adenine (mutated type; 1C) caused a significant decrease of enzyme activity, from cytosine (-164) to adenine (mutated; 1F) caused higher inducibility of CYP1A2. Human CYP2D6 (wild type; 1) were also identified; As for the poor metabolizer, nucleotide sequence alalysis reveale the gene deletion (mutated type; 5) caused a deletion of enzyme activity, from cytosine (100) to thymine (mutated; 10) caused a enzyme activity decrease of CYP2D6. A potential side-effects during the treatment with olanzapine is hyperglycemia and newonset diabetes mellitus. There are possible mechanisms by which olanzapine could interfere with glucose metabolism. In this study, we investigate the relationship between olanzapine metabolism by CYP1A2/CYP2D6 and the side effect (fatality from hyperglysemia) to serve as an aid to solve the mechanisms of olanzapine induced abnormal glucose metabolism into diabetes mellitus among 12 Japanese schizophrenic patients. There were 3 patients whose CYP genotypes showed CYP1A2 1C/wt or CYP2D6 10/10, and whose blood olanzapine concentration was higher (about 40.0ng/mL) inspite of within 10mg daily dose. All these 3 patients did not show hyperglysemia, but other 3 patients whose CYP genotypes were normal, showed hyperglycemia. These results suggested that the higher blood olanzapine concentration may be effected by the abnormal metabolism by CYP1A2 and/or CYP2D6, but not always caused hyper glycemia., P(論文), 特集, application/pdf, FEATURE ARTICLES},
 pages = {123--126},
 title = {精神作用物質の依存および副作用に関連する遺伝子解析 : OlanzapineのCYP1A2およびCYP2D6による代謝},
 volume = {9/10},
 year = {2005},
 yomi = {イワハシ, カズヒコ and ヨシハラ, エイジ and タカダ, ナオコ}
}