Method for individualized evaluation of antiemetic effect induced by 5-HT3 receptor antagonist
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概要
- 論文の詳細を見る
5-HT3 receptor antagonists are widely used for prevention of chemotherapy-induced nausea and vomiting, though their antiemetic effects vary among patients. We investigated a method for evaluation of antiemetic effects in individual patients. We used the 5-HT3 receptor occupancy of serotonin for our evaluation, which was estimated based on the plasma concentration of granisetron and concentration of serotonin near the 5-HT3 receptor in the small intestine, obtained by measuring the urinary concentrations of granisetron and 5-hydroxyindoleaceticacid /creatinine. The mean cumulative percent for urinary excretion of granisetron at 24 hours after administration and coefficient of variation were 16.19±6.30% and 38.91%, respectively. The time course of urinary concentration of 5-hydroxyindoleaceticacid/creatinine also varied among the patients. The value for 5-HT3 receptor occupancy of serotonin without granisetron was higher than that prior to administration (blank), thus most treated patients had the possibility of induced emesis. In contrast, that with granisetron was lower than the blank value, indicating that those treated patients would not develop emesis. Furthermore, the estimated 5-HT3 receptor occupancy of serotonin in the small intestine and actual individual patient condition corresponded well, showing the validity of our method.Our results suggest that it is possible to evaluate individual antiemetic effects by estimating the 5-HT3 receptor occupancy of serotonin in the small intestine based on plasma concentrations of granisetron and serotonin near the 5-HT3 receptor in the small intestine using noninvasive urine samples. This method of individual evaluation is considered to be useful and effective.
- 公益社団法人 日本薬学会の論文
著者
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Yokoyama Haruko
Department Of Biomaterials Institute For Frontier Medical Sciences Kyoto University
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Yamada Yasuhiko
Department Of Clinical Evaluation Of Drug Efficacy School Of Pharmacy Tokyo University Of Pharmacy A
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Okuyama Kiyoshi
Department Of Bioresources Chemistry Chiba University
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Nakamura Hironori
Department Of Applied Physics University Of Fukui
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Yoshimoto Koichi
Department Of Civil And Environmental Engineering Ehime University
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Yamada Yasuhiko
Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Nakajima Akihiro
Department of Hematology, Tokyo Medical University Hachioji Medical Center
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Iwase Osamu
Department of Hematology, Tokyo Medical University Hachioji Medical Center
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Okuyama Kiyoshi
Department of Pharmacy, Tokyo Medical University Hachioji Medical Center
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