Interindividual variations in aprepitant plasma pharmacokinetics in cancer patients receiving cisplatin-based chemotherapy for the first time

• Material Type: 博士論文
• Title: Interindividual variations in aprepitant plasma pharmacokinetics in cancer patients receiving cisplatin-based chemotherapy for the first time
• Volume: 36 4
• Author/Editor: Motohashi, Shinya
• Author Heading: Motohashi, Shinya
• Publication, Distribution, etc.: 日本薬学会
• Publication Date: 2013
• Publication Date (W3CDTF): 2013
• Alternative Title: シスプラチンベースの初回化学療法を受けるがん患者でのアプレピタントの血漿中薬物動態の個体差
• Periodical title: Biological and Pharmaceutical Bulletin
• Degree grantor/type: 浜松医科大学
• Date Granted: 2013-04-19
• Date Granted (W3CDTF): 2013-04-19
• Dissertation Number: 甲第656号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第656号
• Text Language Code: eng
• Subject Heading: aprepitant; pharmacokinetics; total bilirubin; serum albumin; cytochrome P450 3A5
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; The pharmacokinetics of aprepitant, a neurokinin-1 receptor antagonist, have not been fully evaluated in clinical settings. The aim of this study was to characterize the plasma pharmacokinetics of aprepitant and reveal their influence of laboratory tests and cytochrome P450 (CYP) 3A5 gene polymorphisms in cancer patients. Forty-four Japanese cancer patients receiving cisplatin-based chemotherapy for the first time following oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3) were enrolled. The patients did not have gastrointestinal disease and the clinical laboratory values were within their normal reference levels. The plasma concentrations of aprepitant 24 (day 2 predose), 72, and 120 hours after the first aprepitant administration were determined using LC-MS/MS. The relationships between plasma exposure to aprepitant and body weight, clinical laboratory values, age, gender, or CYP3A5*3 were investigated. The median and interquartile ranges of the 120-h area under the plasma concentration time curve (AUC)0-120 of aprepitant were 73215 and 55518-91121 ngh/mL. The coefficient of variation value for aprepitant AUC0-120 was 53%. The AUC0-120 of aprepitant was correlated with the levels of total bilirubin and serum albumin, respectively (r=0.454, p<0.01 and r=0.287, p=0.06), but not with other non-genetic factors and CYP3A5 genetic variants in a univariate analysis. The AUC0-20 of aprepitant was significantly correlated with the level of total bilirubin (adjusted R2=0.187, p<0.01) in a multivariate analysis. In conclusion, the plasma pharmacokinetics of aprepitant varied markedly in cancer patients receiving cisplatin-based chemotherapy for the first time and were correlated with the level of total bilirubin.
• DOI: info:doi/10.1248/bpb.b12-01086; https://doi.org/info:doi/10.1248/bpb.b12-01086
• Persistent ID (NDL): info:ndljp/pid/8949273; https://dl.ndl.go.jp/pid/8949273
• 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）
• Available (W3CDTF): 2015-03-03
• Date Accepted (W3CDTF): 2015-02-03T05:25:05+09:00
• Date Created (W3CDTF): 2018-08-27
• 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): http://hdl.handle.net/10271/2708; https://hama-med.repo.nii.ac.jp/records/2588
• 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

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