Amgen, Inc., Thousand Oaks, CA, USA.
Celerion, Inc., Tempe, AZ, USA.
Clin Pharmacol Drug Dev. 2024 May;13(5):517-533. doi: 10.1002/cpdd.1389. Epub 2024 Feb 29.
Avacopan, a complement 5a receptor (C5aR) antagonist approved for treating severe active antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, was evaluated in 2 clinical drug-drug interaction studies. The studies assessed the impact of avacopan on the pharmacokinetics (PK) of CYP3A4 substrates midazolam and simvastatin and CYP2C9 substrate celecoxib, and the influence of CYP3A4 inhibitor itraconazole and inducer rifampin on the PKs of avacopan. The results indicated that twice-daily oral administration of 30 mg of avacopan increased the area under the curve (AUC) of midazolam by 1.81-fold and celecoxib by 1.15-fold when administered without food, and twice-daily oral administration of 30 or 60 mg of avacopan increased the AUC of simvastatin by approximately 2.6-3.5-fold and the AUC of the active metabolite β-hydroxy-simvastatin acid by approximately 1.4-1.7-fold when co-administered with food. Furthermore, the AUC of avacopan increased by approximately 2.19-fold when co-administered with itraconazole and decreased by approximately 13.5-fold when co-administered with rifampin. These findings provide critical insights into the potential drug-drug interactions involving avacopan, which could have significant implications for patient care and treatment planning. (NCT06207682).
阿瓦考潘是一种补体 5a 受体（C5aR）拮抗剂，已被批准用于治疗严重的抗中性粒细胞胞质抗体（ANCA）相关性血管炎，在两项临床药物相互作用研究中进行了评估。这些研究评估了阿瓦考潘对细胞色素 P450（CYP）3A4 底物咪达唑仑和辛伐他汀以及 CYP2C9 底物塞来昔布的药代动力学（PK）的影响，以及 CYP3A4 抑制剂伊曲康唑和诱导剂利福平对阿瓦考潘 PK 的影响。结果表明，在空腹时，每天两次口服 30mg 阿瓦考潘可使咪达唑仑的 AUC 增加 1.81 倍，塞来昔布的 AUC 增加 1.15 倍；当与食物同服时，每天两次口服 30 或 60mg 阿瓦考潘可使辛伐他汀的 AUC 增加约 2.6-3.5 倍，β-羟基辛伐他汀酸的 AUC 增加约 1.4-1.7 倍。此外，当与伊曲康唑合用时，阿瓦考潘的 AUC 增加约 2.19 倍，当与利福平合用时，阿瓦考潘的 AUC 减少约 13.5 倍。这些发现为涉及阿瓦考潘的潜在药物相互作用提供了重要的见解，这可能对患者的护理和治疗计划有重大影响。（NCT06207682）。
