先进乳腺癌通常为激素受体（HR）阳性和人表皮生长因子受体2（HER2）阴性。其中一些患者在PIK3CA基因中携带突变，该基因编码磷脂酰肌醇3激酶（PI3K）的p110α催化亚基，从而使激素治疗失效。Alpelisib是FDA和EMA批准的第一种口服选择性p110 [Formula：见本文] PI3K抑制剂，与富莱斯汀合用，相比单用富莱斯汀改善PFS。本综述的目的是总结和批判性地评估Alpelisib药代动力学（PK）和药效学（PD）的关键方面。临床前数据显示，相对于β、δ和γ PI3K酶，Alpelisib IC50对α酶低50倍，导致肿瘤内AKT磷酸化降低。Alpelisib的PK特性某种程度上比较有利，具有快速和重要的吸收，有限的CYP P450介导的代谢以及突出的胆汁排泄，半衰期为17.5±5.9小时。只预期会有有限的药物相互作用，并且在轻度和中度肾功能受损以及轻度至严重肝功能受损患者中不需要剂量适应。药物开发期间证实了药代动力学/药效学关系，包括曝光/疗效以及曝光/安全性。主要的不良事件包括高血糖、皮疹和腹泻。首先，如果非常见禁忌症，需在治疗开始时密切监测，并在必要时减少剂量。由于其安全特性，Alpelisib需要进行严格的患者选择和密切的随访。© 2023年。作者向Springer Nature Switzerland AG独家许可。

Advanced breast cancers are frequently hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative. Some of them harbor a mutation in PIK3CA, a gene encoding the PI3K catalytic subunit α of phosphatidyl-inositol 3-kinase (PI3K), which confers resistance to hormone therapy. Alpelisib is the first oral selective p110 [Formula: see text] PI3K inhibitor approved by FDA and EMA, in association with fulvestrant, based on PFS improvement as compared to fulvestrant alone. The aim of this review is to summarize and critically review the key aspects of alpelisib pharmacokinetics (PK) and pharmacodynamics (PD). Preclinical data have shown that alpelisib IC50 was 50 times lower for the α enzyme than for the β, δ and γ PI3K enzymes, leading to a decrease in intra-tumoral AKT phosphorylation. The PK properties of alpelisib are somehow favorable, with a rapid and important absorption, a limited CYP P450-mediated metabolism and a predominant biliary excretion, with a half-life of 17.5 ± 5.9 h. Only limited drug-drug interactions are expected and there is no need for dose adaptation in mild and moderate renal impaired and mild to severe hepatic impaired patients. Pharmacokinetic/pharmacodynamic relationships were evidenced during drug development for exposure/efficacy, but also exposure/safety. Main adverse events are hyperglycemia, rash, and diarrhea. The first, if not fully contra-indicated in (pre-)diabetic patients, warrants a close follow up when treatment is started and a potential dose reduction when needed. Because of its safety profile, alpelisib require stringent patient selection and close follow-up.© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.