著者

杉山 暢宏 田名部 はるか

出版者

信州医学会

雑誌

信州医学雑誌 (ISSN:00373826)

巻号頁・発行日

vol.66, no.3, pp.185-193, 2018-06-10 (Released:2018-07-27)

参考文献数

53

著者

寺澤 美穂 山折 大 勝山 善彦 二村 緑 久富 由里子 田中 章 荻原 朋美 萩原 徹也 杉山 暢宏 鷲塚 伸介 大森 栄

出版者

一般社団法人日本医療薬学会

雑誌

医療薬学 (ISSN:1346342X)

巻号頁・発行日

vol.43, no.7, pp.362-372, 2017-07-10 (Released:2018-07-10)

参考文献数

23

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This study analyzed factors affecting plasma lamotrigine (LTG) concentrations in patients with bipolar disorder. The mean concentration/dose (C/D) ratio of LTG was significantly higher in patients co-treated with LTG and valproic acid (VPA) [3.72 (μg/mL)/(mg/kg/day), n = 9] than in those receiving LTG monotherapy [1.76 (μg/mL)/(mg/kg/day), n = 9; P < 0.01]. LTG monotherapy patients were genotyped for UDP-glucuronosyltransferase 2B7 (UGT2B7) *1/*1 (n = 5) and *1/*2(n = 4), whereas VPA co-administration patients were genotyped for UGT2B7*1/*1 (n = 6), *1/*2 (n = 2) and *2/*2 (n = 1). *There were no significant differences in mean C/D ratios between patients carrying the UGT2B7*1/*1 genotype and the 1/*2 or *2/*2 genotype regardless of pharmacotherapy (P ≥ 0.150). In the LTG monotherapy group, the mean C/D ratio was similar in smoking patients [1.52 (μg/mL)/(mg/kg/day), n = 3] and non-smoking patients [1.88 (μg/mL)/(mg/kg/day), n = 6; P = 0.393]. In the VPA co-administration group, however, the mean C/D ratio in smoking patients [2.62 (μg/mL)/(mg/kg/day), n = 4] was significantly lower than that in non-smoking patients [4.61 (μg/mL)/(mg/kg/day), n = 5; P < 0.01]. In vitro studies with HepG2 cells indicated that benzo[a]pyrene, one of the polycyclic aromatic hydrocarbons contained in tobacco smoke, as well as 3-methylcholanthrene efficiently induced expression of UGT1A4 mRNA but not UGT2B7 mRNA and that VPA potently enhanced their induction. These results suggest that concomitant VPA administration and/or smoking may influence LTG concentrations in patients with bipolar disorder.

著者

杉山 暢宏 田名部 はるか

出版者

信州医学会

雑誌

信州医誌 (ISSN:00373826)

巻号頁・発行日

vol.66, no.3, pp.185-193, 2018