- 英名:Axitinib
- 商品名:インライタ錠(ファイザー株式会社)
- 消失臓器:肝代謝型
- CL:中間
- Vd:大
- タンパク結合:binding sensitive
- EH = 21(L/hr)/800(mL/min) = 0.435
- 1-F = 0.42
- Vd = 68(L)≧50(L)
- 健康成人16例にアキシチニブを静脈内投与注)(1mg)したときの分布容積の平均値(変動係数)は68L(23%)(添付文書)
- アキシチニブの血漿蛋白結合率(平衡透析法、0.2〜20μg/mL)に関して、濃度依存性は認められず、99.5%であった(in vitro試験)(添付文書)
- 主にCYP3A4/5、一部はCYP1A2、CYP2C19又はUGT1A1によって代謝(添付文書)
- 静脈内投与注)(1mg)したときの全身クリアランスの平均値(変動係数)は21L/h(44%)(添付文書)
- 臨床的に影響を与えうる代謝物なし
- 血漿中の主代謝物は、グルクロン酸抱合体及びスルホキシド体(添付文書)
- グルクロン酸抱合体及びスルホキシド体のVEGFR-2のリン酸化阻害作用は、未変化体のそれぞれ約1/8000及び1/400倍(添付文書)
- 腎機能低下者を対象にした薬物動態試験は実施していない(添付文書)
- 健康成人及び癌患者を対象に母集団薬物動態解析を実施している(590例)
- 腎機能をCLcr(mL/min)に基づいて分類
- 90mL/min以上(正常腎機能、381例):14.0L/h
- 60〜89mL/min(軽度腎機能低下、139例):10.7L/h
- 30〜59mL/min(中等度腎機能低下、64例):12.3L/h
- 15〜29mL/min(重度腎機能低下、5例):7.81L/h
- 15mL/min未満[末期腎疾患(ESRD)1例]:12.6L/h
- 腎機能をCLcr(mL/min)に基づいて分類
- 影響あり
- 軽度の肝機能障害を有する被験者におけるアキシチニブのCmax及びAUC0-∞は、健康被験者のそれぞれ0.89及び0.78倍(添付文書)
- 中等度の肝機能障害を有する被験者におけるアキシチニブのCmax及びAUC0-∞は、健康被験者のそれぞれ1.28及び1.95倍に上昇(添付文書)
- 重度(Child-Pugh分類C)の肝機能障害を有する被験者を対象とした臨床試験は実施していない(添付文書)
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- Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments.
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- Population pharmacokinetic analysis of axitinib in healthy volunteers.
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- Axitinib plasma pharmacokinetics and ethnic differences.
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- Clin Pharmacokinet. 2015 Apr;54(4):397-407. doi: 10.1007/s40262-014-0207-5.
- Population pharmacokinetic-pharmacodynamic modelling of 24-h diastolic ambulatory blood pressure changes mediated by axitinib in patients with metastatic renal cell carcinoma.
- PMID: 25343945 https://www.ncbi.nlm.nih.gov/pubmed/25343945
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- Lack of effect of smoking status on axitinib pharmacokinetics in patients with non-small-cell lung cancer.
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- Effect of Renal Impairment on the Pharmacokinetics and Safety of Axitinib.
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