The management of pulmonary arterial hypertension (PAH) has become more complex in recent years because of increased pharmacotherapy options and longer patient survival with increasing numbers of comorbidities. As such, more opportunities exist for drug-drug interactions between PAH-targeted medications and medications potentially used to treat comorbid conditions. In this review, we provide an overview of pharmaceutical metabolism by cytochrome P450 and discuss important drug-drug interactions for the 14 Food and Drug Administration-approved medications for PAH in the nitric oxide (NO), endothelin, and prostacyclin pathways. Among the targets in the NO pathway (sildenafil, tadalafil, and riociguat), important interactions with nitrates, protease inhibitors, and other phosphodiesterase inhibitors can cause profound hypotension. In the endothelin pathway, bosentan is associated with more drug interactions via CYP3A4 inhibition; macitentan and ambrisentan have fewer interactions of note. Although the parenteral therapies in the prostacyclin pathway bypass significant liver metabolism and avoid drug interactions, selexipag and oral treprostinil may exhibit interactions with CYP2C8 inhibitors such as gemfibrozil and clopidogrel, which can raise drug levels. Finally, we provide a framework for identifying potential drug-drug interactions and avoiding errors.

肺动脉高压 (PAH) 的管理近年来变得更加复杂，因为药物治疗选择的增加和患者存活时间的延长以及合并症数量的增加。因此，PAH 靶向药物和可能用于治疗合并症的药物之间存在更多的药物相互作用机会。在这篇综述中，我们概述了细胞色素 P450 的药物代谢，并讨论了 14 种经美国食品和药物管理局批准的药物在一氧化氮 (NO)、内皮素和前列环素途径中用于治疗 PAH 的重要药物相互作用。在 NO 通路的靶标（西地那非、他达拉非和利奥西呱）中，与硝酸盐、蛋白酶抑制剂和其他磷酸二酯酶抑制剂的重要相互作用可导致严重低血压。在内皮素途径中，波生坦通过抑制 CYP3A4 与更多药物相互作用相关；macitentan 和 ambrisentan 的相互作用较少。尽管前列环素通路中的肠胃外疗法绕过了显着的肝脏代谢并避免了药物相互作用，但司来帕格和口服曲前列环素可能会与 CYP2C8 抑制剂（如吉非贝齐和氯吡格雷）发生相互作用，从而提高药物水平。最后，我们提供了一个框架来识别潜在的药物相互作用和避免错误。selexipag 和口服曲前列尼可能会与 CYP2C8 抑制剂（例如吉非贝齐和氯吡格雷）发生相互作用，从而提高药物水平。最后，我们提供了一个框架来识别潜在的药物相互作用和避免错误。selexipag 和口服曲前列尼可能会与 CYP2C8 抑制剂（例如吉非贝齐和氯吡格雷）发生相互作用，从而提高药物水平。最后，我们提供了一个框架来识别潜在的药物相互作用和避免错误。