Department of Pharmacy, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Kanagawa, Japan.
Division of Bioanalytical Chemistry, Graduate School of Pharmacy, Tokyo, Japan.
Biomed Chromatogr. 2023 May;37(5):e5599. doi: 10.1002/bmc.5599. Epub 2023 Feb 21.
Cabozantinib is an oral small-molecule tyrosine kinase inhibitor that has become a standard of care for advanced renal cell carcinoma (RCC). However, cabozantinib is associated with a high rate of adverse events. Therefore, individualised cabozantinib administration and monitoring could help maximise its therapeutic efficacy and avoid serious adverse events. This study developed and validated a method to determine cabozantinib concentration in plasma using HPLC-UV. Sorafenib, an internal standard, was added to the plasma sample containing cabozantinib. A calibration curve for cabozantinib showed good linearity (R = 1.00), between 25 and 4,000 ng/ml. The recovery rate was above 92.1%, and the intra- and inter-day coefficients of variation were smaller than 5.2 and 6.8%, respectively. Then, we applied the method for monitoring cabozantinib blood levels in three patients with advanced RCC who were taking cabozantinib at a dose of 20, 40 or 60 mg/day. Grade 3 adverse events were more likely to occur in patients with high dosing and blood level of cabozantinib. Owing to its simplicity, the developed method can be used in general hospitals, and is expected to help maximise drug efficacy and minimise serious adverse events in many patients with RCC undergoing cabozantinib treatment.
卡博替尼是一种口服小分子酪氨酸激酶抑制剂，已成为晚期肾细胞癌（RCC）的标准治疗方法。然而，卡博替尼与高不良事件发生率相关。因此，个体化卡博替尼给药和监测可能有助于最大限度地提高其治疗效果并避免严重的不良事件。本研究开发并验证了一种使用 HPLC-UV 测定血浆中卡博替尼浓度的方法。索拉非尼是一种内标，添加到含有卡博替尼的血浆样本中。卡博替尼的校准曲线显示出良好的线性关系（R = 1.00），范围在 25 至 4000ng/ml 之间。回收率高于 92.1%，日内和日间变异系数均小于 5.2%和 6.8%。然后，我们应用该方法监测了 3 名每天服用卡博替尼 20、40 或 60mg 的晚期 RCC 患者的卡博替尼血药水平。高剂量和高血药水平的卡博替尼患者更有可能发生 3 级不良事件。由于其简单性，所开发的方法可以在综合医院使用，有望帮助许多接受卡博替尼治疗的 RCC 患者最大限度地提高药物疗效并最小化严重不良事件。
