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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Evaluation of the effect of food and gastric pH on the single-dose pharmacokinetics of cabozantinib in healthy adult subjects
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Evaluation of the effect of food and gastric pH on the single-dose pharmacokinetics of cabozantinib in healthy adult subjects

机译：评估食物和胃中pH值对健康成人受试者卡博替尼单剂量药代动力学的影响

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摘要

Cabozantinib is a small molecule tyrosine kinase inhibitor that has been approved for the treatment of patients with progressive, metastatic medullary thyroid cancer. Cabozantinib exhibits a pH-dependent solubility profile in vitro. Two phase 1 clinical pharmacology studies were conducted in healthy subjects to evaluate whether factors that may affect cabozantinib solubility and gastric pH could alter cabozantinib bioavailability: a food effect study (study 1) and a drug-drug interaction (DDI) study with the proton pump inhibitor (PPI) esomeprazole (study 2). Following a high-fat meal (study 1), cabozantinib C-max and AUC were increased (40.5% and 57%, respectively), and the median t(max) was delayed by 2 hours. Cabozantinib should thus not be taken with food (patients should not eat for at least 2 hours before and at least 1 hour after administration). In the DDI study (study 2), the 90% confidence intervals (CIs) around the ratio of least-squares means of cabozantinib with esomeprazole versus cabozantinib alone for AUC(0-inf) were within the 80%-125% limits; the upper 90%CI for C-max was 125.1%. Because of the low apparent risk of a DDI, concomitant use of PPIs or weaker gastric pH-altering agents with cabozantinib is not contraindicated.
机译：Cabozantinib是一种小分子酪氨酸激酶抑制剂，已被批准用于治疗进行性转移性甲状腺髓样癌患者。卡波替尼在体外具有pH依赖性的溶解度特征。在健康受试者中进行了两项1期临床药理学研究，以评估可能影响卡博替尼溶解度和胃pH值的因素是否会改变卡博替尼的生物利用度：一项食品效果研究（研究1）和质子泵的药物相互作用研究（DDI）抑制剂（PPI）埃索美拉唑（研究2）。高脂餐后（研究1），卡波替尼C-max和AUC升高（分别为40.5％和57％），中位t（max）延迟2小时。因此，卡波替尼不宜与食物一起服用（患者在给药前至少2小时和给药后至少1小时不应进食）。在DDI研究中（研究2），AUC（0-inf）的卡博替尼与埃索美拉唑相对于单独的卡博替尼的最小二乘均方比的90％置信区间（CIs）在80％-125％的范围内; C-max的最高90％CI为125.1％。由于DDI的表观风险较低，因此不建议与卡波替尼同时使用PPI或较弱的胃pH改变剂。

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