Nishida Kazuki, Liang Yao, Maeda Osamu, Silva Angélique Da, Ando Yuichi, Chrétien Basile
Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan.
Department of Biostatistics, Kyoto University School of Public Health, Kyoto, Japan.
Cancer Chemother Pharmacol. 2025 Jul 2;95(1):66. doi: 10.1007/s00280-025-04792-7.
Pazopanib, a multi-targeted tyrosine kinase inhibitor, is used for advanced renal cell carcinoma and soft tissue sarcoma. However, it is associated with dose-dependent adverse events (AEs), including hypertension, and gastrointestinal issues. Antacids like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are often co-administered, raising concerns about potential drug interactions. Pazopanib's solubility and absorption are pH-dependent, with increased gastric pH potentially reducing its bioavailability. In this study, we analyzed VigiBase data using multivariate logistic regression models and found significant interactions between pazopanib and antacids (PPIs, H2RAs, and others), suggesting reduced serious AE reporting, possibly due to lower pazopanib exposure. A secondary analysis of CYP3A4 inhibitors showed a non-significant trend for higher serious AEs, aligning with expected pharmacokinetic effects. These findings emphasize the need for caution when combining antacids with pazopanib, as it may reduce both toxicity and efficacy.
帕唑帕尼是一种多靶点酪氨酸激酶抑制剂，用于治疗晚期肾细胞癌和软组织肉瘤。然而，它与剂量依赖性不良事件（AE）相关，包括高血压和胃肠道问题。质子泵抑制剂（PPI）和组胺-2受体拮抗剂（H2RA）等抗酸剂常与帕唑帕尼联合使用，这引发了对潜在药物相互作用的担忧。帕唑帕尼的溶解度和吸收依赖于pH值，胃内pH值升高可能会降低其生物利用度。在本研究中，我们使用多变量逻辑回归模型分析了VigiBase数据，发现帕唑帕尼与抗酸剂（PPI、H2RA及其他）之间存在显著相互作用，提示严重AE报告减少，可能是由于帕唑帕尼暴露量降低。对CYP3A4抑制剂的二次分析显示，严重AE有升高的非显著趋势，这与预期的药代动力学效应一致。这些发现强调了抗酸剂与帕唑帕尼联合使用时需谨慎，因为这可能会降低毒性和疗效。
