Department of Anesthesiology, Shanghai Pulmonary Hospital, Shanghai, China.
Department of Endocrine, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Pharm Biol. 2022 Dec;60(1):1944-1948. doi: 10.1080/13880209.2022.2125539.
The co-administration of abemaciclib and astragaloside IV might occur in the treatment of breast cancer.
This study evaluates the interaction between abemaciclib and astragaloside IV in rats and describes the potential mechanism.
Male Sprague Dawley rats were randomly divided into four groups: single dose of abemaciclib (control), abemaciclib + 50 mg/kg/d astragaloside IV, abemaciclib + 100 mg/kg/d astragaloside IV, and abemaciclib + 150 mg/kg/d astragaloside IV. Abemaciclib and astragaloside IV were orally administrated, and astragaloside IV was pre-administrated for 7 d in the co-administrated groups. The pharmacokinetics and transport of abemaciclib were assessed in the absence or presence of astragaloside IV. In mechanism, the activity of CYP3A4 was estimated in human liver microsomes in the presence of astragaloside IV.
Astragaloside IV significantly increased the C (from 991.5 ± 116.99 up to 2308.5 ± 55.29 μg/L) and AUC (from 24.49 ± 2.86 up to 66.14 ± 1.17 μg/mL × h) and prolonged the t (from 19.85 ± 4.65 up to 66.17 ± 28.73 h) of abemaciclib, and the effect was enhanced with the increasing astragaloside IV concentration. Astragaloside IV also suppressed the transport of abemaciclib with the efflux ratio decreasing to 1.35. Astragaloside IV suppressed the activity of CYP3A4 with an IC value of 21.78 μM.
The co-administration of abemaciclib and astragaloside IV induced the increasing systemic exposure of abemaciclib through the inhibition of CYP3A4. Further clinical validations could be carried out according to the study design of the present investigation.
阿贝西利与黄芪甲苷 IV 合用时可能发生于乳腺癌的治疗中。
本研究评估了阿贝西利与黄芪甲苷 IV 在大鼠体内的相互作用，并描述了潜在的作用机制。
雄性 Sprague Dawley 大鼠随机分为四组：单剂量阿贝西利（对照组）、阿贝西利+50mg/kg/d 黄芪甲苷 IV、阿贝西利+100mg/kg/d 黄芪甲苷 IV 和阿贝西利+150mg/kg/d 黄芪甲苷 IV。阿贝西利和黄芪甲苷 IV 经口给药，合用组中黄芪甲苷 IV 预先给药 7d。在无或有黄芪甲苷 IV 的情况下评估阿贝西利的药代动力学和转运。在机制方面，评估了黄芪甲苷 IV 存在时人肝微粒体中 CYP3A4 的活性。
黄芪甲苷 IV 显著增加了阿贝西利的 C（从 991.5±116.99 增加至 2308.5±55.29μg/L）和 AUC（从 24.49±2.86 增加至 66.14±1.17μg/mL×h），并延长了 t（从 19.85±4.65 增加至 66.17±28.73h），且随着黄芪甲苷 IV 浓度的增加，作用增强。黄芪甲苷 IV 还抑制了阿贝西利的转运，使外排比降至 1.35。黄芪甲苷 IV 对 CYP3A4 的抑制作用的 IC 值为 21.78μM。
阿贝西利与黄芪甲苷 IV 合用时，通过抑制 CYP3A4 导致阿贝西利的全身暴露增加。可根据本研究的设计进行进一步的临床验证。
