关键词: Pazopanib Therapeutic drug monitoring (TDM) Ultraviolet (UV) spectroscopy

Mesh : Humans Carcinoma, Renal Cell / drug therapy pathology secondary Kidney Neoplasms / chemically induced drug therapy pathology Drug Monitoring Pyrimidines Indazoles Sulfonamides

来  源:   DOI:10.1208/s12248-024-00918-6

Abstract:
Pazopanib is a multi-kinase inhibitor used to treat advanced/metastatic renal cell carcinoma and advanced soft tissue tumors; however, side effects such as diarrhea and hypertension have been reported, and dosage adjustment based on drug concentration in the blood is necessary. However, measuring pazopanib concentrations in blood using the existing methods is time-consuming; and current dosage adjustments are made using the results of blood samples taken at the patient\'s previous hospital visit (approximately a month prior). If the concentration of pazopanib could be measured during the waiting period for a doctor\'s examination at the hospital (in approximately 30 min), the dosage could be adjusted according to the patient\'s condition on that day. Therefore, we aimed to develop a method for rapidly measuring blood pazopanib concentrations (in approximately 25 min) using common analytical devices (a tabletop centrifuge and a spectrometer). This method allowed for pazopanib quantification in the therapeutic concentration range (25-50 μg/mL). Additionally, eight popular concomitant medications taken simultaneously with pazopanib did not interfere with the measurements. We used the developed method to measure blood concentration in two patients and obtained similar results to those measured using the previously reported HPLC method. By integrating it with the point of care and sample collection by finger pick, this method can be used for measurements in pharmacies and patients\' homes. This method can maximize the therapeutic effects of pazopanib by dose adjustment to control adverse events.
摘要:
帕唑帕尼是一种多激酶抑制剂,用于治疗晚期/转移性肾细胞癌和晚期软组织肿瘤;然而,已经报道了腹泻和高血压等副作用,根据血液中的药物浓度调整剂量是必要的。然而,使用现有方法测量血液中的帕唑帕尼浓度是耗时的;当前的剂量调整是使用患者先前住院时(大约一个月前)采集的血样结果进行的.如果帕唑帕尼的浓度可以在等待期间在医院进行医生检查(大约30分钟),剂量可以根据患者当天的病情进行调整。因此,我们的目的是开发一种使用普通分析设备(台式离心机和光谱仪)快速测量血液帕唑帕尼浓度(大约25分钟)的方法。该方法允许在治疗浓度范围(25-50μg/mL)内定量帕唑帕尼。此外,与帕唑帕尼同时服用的八种流行的合并用药不会干扰测量.我们使用开发的方法来测量两名患者的血液浓度,并获得了与使用先前报道的HPLC方法测量的结果相似的结果。通过将其与护理点和手指采集样本相结合,该方法可用于药房和患者家中的测量。该方法可以通过剂量调整以控制不良事件来最大化帕唑帕尼的治疗效果。
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