Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.
Intensive Care Unit, Shaanxi Traditional Chinese Medicine Hospital, Xi'an, China.
Clin Pharmacol Drug Dev. 2022 Jun;11(6):687-694. doi: 10.1002/cpdd.1099. Epub 2022 Apr 29.
Anastrozole is a third-generation aromatase inhibitor that exerts potent anti-breast cancer effects. This trial aimed to explore the pharmacokinetics (PK) and safety with bioequivalence of orally administered anastrozole provided by 2 sponsors in healthy volunteers.Two separate open-label, randomized, single-dose, crossover-design studies consisting of a fasting study (n = 23) and a fed study (n = 23, 1 participant withdrew before taking medication) were conducted. In each study, healthy volunteers were randomized to receive the test product (Haizheng Pharmaceutical Group) followed by the reference drug (AstraZeneca Pharmaceuticals LP), or vice versa. Each study subject received a 1-mg anastrozole tablet with a 21-day washout. The plasma concentrations of anastrozole were measured with liquid chromatography-tandem mass spectrometry, and PK parameters were determined by noncompartmental analysis. Forty-six healthy female volunteers were enrolled. For patients enrolled in the fasting study, the mean age was 55.0 years, mean weight was 57.1 kg, mean body mass index was 23.6 kg/m , and mean height was 155.5 cm. For patients enrolled in the fed study, the mean age was 54.2 years, mean weight was 55.9 kg, mean body mass index was 23.9 kg/m and mean height was 152.8 cm. All PK end points met the predefined criteria for PK equivalence. In fasting subjects, the median maximum plasma concentration was 23.4 and 22.6 at 1 hour for test and reference formulations, respectively. The maximum plasma concentration in fed subjects was 18.7 and 18.5 at 4 hours for test and reference formulations, respectively. Both fasting and fed studies achieved plausible bioequivalence. Anastrozole was well tolerated and exhibited a favorable safety profile at the prescribed doses. The severity of observed adverse events assessed according to the Common Terminology Criteria for Adverse Events (version CTCAE4.03) was mild, and some of the adverse events were not caused by anastrozole. Furthermore, the results of our study under fasting and fed conditions demonstrated bioequivalence of the test and reference products.
阿那曲唑是第三代芳香化酶抑制剂，具有强大的抗乳腺癌作用。本试验旨在探索 2 家赞助商提供的口服阿那曲唑在健康志愿者中的药代动力学（PK）和生物等效性安全性。进行了两项单独的开放标签、随机、单剂量、交叉设计研究，包括禁食研究（n=23）和进食研究（n=23，1 名参与者在服药前退出）。在每项研究中，健康志愿者被随机分配接受受试产品（海正药业集团）后接受参比药物（阿斯利康制药有限公司），或反之亦然。每个研究对象接受 1 毫克阿那曲唑片，洗脱期 21 天。阿那曲唑的血浆浓度用液相色谱-串联质谱法测定，PK 参数用非房室分析确定。共纳入 46 名健康女性志愿者。参加禁食研究的患者平均年龄为 55.0 岁，平均体重为 57.1kg，平均体重指数为 23.6kg/m ，平均身高为 155.5cm。参加进食研究的患者平均年龄为 54.2 岁，平均体重为 55.9kg，平均体重指数为 23.9kg/m ，平均身高为 152.8cm。所有 PK 终点均符合 PK 等效性的预设标准。在禁食受试者中，受试和参比制剂的最大血浆浓度中位数分别为 1 小时时的 23.4 和 22.6ng/ml。进食受试者的最大血浆浓度分别为 4 小时时的 18.7 和 18.5ng/ml。禁食和进食研究均达到合理的生物等效性。阿那曲唑在规定剂量下耐受良好，安全性良好。根据不良事件通用术语标准（CTCAE4.03 版）评估的观察到的不良事件的严重程度为轻度，一些不良事件不是由阿那曲唑引起的。此外，我们在禁食和进食条件下的研究结果表明，受试和参比产品具有生物等效性。
