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

著者

    • Motohashi, Shinya
    • 本橋, 慎也

書誌事項

タイトル

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

タイトル別名

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

著者名

Motohashi, Shinya

著者名

本橋, 慎也

学位授与大学

浜松医科大学

取得学位

博士(医学)

学位授与番号

甲第656号

学位授与年月日

2013-04-19

注記・抄録

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 h 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 ng h/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 AUC0–120 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.

浜松医科大学学位論文 医博第656号(平成25年4月19日)

PubMed番号 : info:pmid/23370406

医中誌ID : N405330023

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各種コード

  • NII論文ID(NAID)
    500000731892
  • NII著者ID(NRID)
    • 8000000891969
    • 8000000891970
  • DOI(出版社)
  • DOI
  • 本文言語コード
    • eng
  • データ提供元
    • 機関リポジトリ
    • NDLデジタルコレクション
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