Impact of the Catechol-O-Methyltransferase Val158Met Polymorphism on the Pharmacokinetics of L-dopa and its Metabolite 3-O-Methyldopa in Combination with Entacapone （エンタカポン併用下におけるL-dopaおよびその代謝物である3-O-メチルドパの体内動態に及ぼすカテコール-O-メチルトランスフェラーゼVal158Met遺伝子多型の影響に関する研究）

• Material Type: 博士論文
• ISSN: 0300-9564
• Title: Impact of the Catechol-O-Methyltransferase Val158Met Polymorphism on the Pharmacokinetics of L-dopa and its Metabolite 3-O-Methyldopa in Combination with Entacapone （エンタカポン併用下におけるL-dopaおよびその代謝物である3-O-メチルドパの体内動態に及ぼすカテコール-O-メチルトランスフェラーゼVal158Met遺伝子多型の影響に関する研究）
• Volume: 128 1
• Author/Editor: 山本, 譲
• Author Heading: 山本, 譲
• Publication Date: 2021-01
• Publication Date (W3CDTF): 2021-01
• Periodical title: Journal of Neural Transmission
• Degree grantor/type: 旭川医科大学
• Date Granted: 2021-09-30
• Date Granted (W3CDTF): 2021-09-30
• Dissertation Number: 乙第490号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 乙第490号
• Text Language Code: eng
• Subject Heading: 3-O-Methyldopa; Catechol-O-methyl transferase; Entacapone; L-dopa; Parkinson’s disease; Polymorphism
• Target Audience: 一般
• Note (General): type:application/pdf; In the pharmacotherapy of patients with Parkinson's disease (PD), entacapone reduces the peripheral metabolism of L-dopa to 3-O-methyldopa (3-OMD), thereby prolonging the half-life (t1/2) of L-dopa and increasing the area under the concentration curve (AUC). The effect of entacapone on the pharmacokinetics of L-dopa differs between patients with high-activity (H/H) and low-activity (L/L) catechol-O-methyltransferase (COMT) Val158Met polymorphisms, but the effects are unclear in heterozygous (H/L) patients. 3-OMD has a detrimental effect and results in a poor response to L-dopa treatment in patients with PD; however, the influence of this polymorphism on the production of 3-OMD remains unknown. Therefore, the present study aimed to clarify the effect of the COMT Val158Met polymorphism on the concentrations of L-dopa and 3-OMD in the presence of entacapone. We performed an open-label, single-period, single-sequence crossover study at two sites in Japan. The study included 54 Japanese patients with PD, who underwent an acute L-dopa administration test with and without 100 mg entacapone on two different days. Entacapone increased L-dopa AUC0-infinity by 1.59 ± 0.26-fold in the H/H group, which was significantly higher than that in the H/L (1.41 ± 0.36-fold) and L/L (1.28 ± 0.21-fold) groups (p < 0.05). The concurrent administration of L-dopa with entacapone suppressed the increase in 3-OMD levels compared with L-dopa alone in all genotypes. Our results suggest that the COMT Val158Met polymorphism may be an informative biomarker for individualized dose adjustment of COMT inhibitors in the treatment of PD.; identifier:PMID:33136226
• DOI: info:doi/10.1007/s00702-020-02267-y; https://doi.org/info:doi/10.1007/s00702-020-02267-y
• Persistent ID (NDL): info:ndljp/pid/12314264; https://dl.ndl.go.jp/pid/12314264
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2022-08-08T06:02:54+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): https://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20210930_O490
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp