Interindividual Variations in Aprepitant Plasma Pharmacokinetics in Cancer Patients Receiving Cisplatin-Based Chemotherapy for the First Time
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概要
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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.
著者
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NAITO Takafumi
Department of Clinical Pharmacy, Oita Medical University
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MINO Yasuaki
Department of Hospital Pharmacy, Hamamatsu University School of Medicine
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FURUSE Hiroshi
Department of Urology, Hamamatsu University School of Medicine
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Mineta Hiroyuki
Department Of Otolaryngology Hamamatsu University School Of Medicine
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Furuse Hiroshi
Department Of Urology Hamamatsu University School Of Medicine
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Ozono Seiichiro
Department Of Hamamatsu University School Of Medicine
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Kawakami Junichi
Department Of Hospital Pharmacy Hamamatsu University School Of Medicine
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Motohashi Shinya
Department Of Thoracic And Cardiovascular Surgery Tachikawa General Hospital
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Hori Katsuhito
Department of Hospital Pharmacy, Hamamatsu University School of Medicine
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Hosokawa Seiji
Department of Otorhinolaryngology/Head & Neck Surgery, Hamamatsu University School of Medicine
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Mineta Hiroyuki
Department of Otorhinolaryngology/Head & Neck Surgery, Hamamatsu University School of Medicine
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