Sidharta P N, Treiber A, Dingemanse J
Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123, Allschwil, Switzerland,
Clin Pharmacokinet. 2015 May;54(5):457-71. doi: 10.1007/s40262-015-0255-5.
Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vascular system, which leads to right-sided heart failure and ultimately death if untreated. Treatments to regulate the pulmonary vascular pressure target the prostacyclin, nitric oxide, and endothelin (ET) pathways. Macitentan, an oral, once-daily, dual ETA and ETB receptor antagonist with high affinity and sustained receptor binding is the first ET receptor antagonist to show significant reduction of the risk of morbidity and mortality in PAH patients in a large-scale phase III study with a long-term outcome. Here we present a review of the available clinical pharmacokinetic, pharmacodynamic, pharmacokinetic/pharmacodynamic relationship, and drug-drug interaction data of macitentan in healthy subjects, patients with PAH, and in special populations.
肺动脉高压（PAH）是一种肺部血管系统的进行性疾病，如果不进行治疗，会导致右心衰竭并最终死亡。调节肺血管压力的治疗方法针对前列环素、一氧化氮和内皮素（ET）途径。马昔腾坦是一种口服、每日一次的双重ETA和ETB受体拮抗剂，具有高亲和力和持续的受体结合能力，是首个在一项具有长期结果的大规模III期研究中显示能显著降低PAH患者发病和死亡风险的ET受体拮抗剂。在此，我们对马昔腾坦在健康受试者、PAH患者及特殊人群中的现有临床药代动力学、药效学、药代动力学/药效学关系和药物相互作用数据进行综述。
