School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Jiangsu, China.
Pharm Biol. 2022 Dec;60(1):1190-1197. doi: 10.1080/13880209.2022.2087688.
Ginkgo leaf tablet (GLT), a traditional Chinese herbal formula, is often combined with rosiglitazone (ROS) for type 2 diabetes mellitus treatment. However, the drug-drug interaction between GLT and ROS remains unknown.
To investigate the effects of GLT on the pharmacokinetics of ROS and its potential mechanism.
The pharmacokinetics of 10 mg/kg ROS with 100/200 mg/kg GLT as single-dose and 10-day multiple-dose administration were investigated in Sprague-Dawley rats. , the effects of GLT on the activity of CYP2C8 and CYP2C9 were determined in recombinant human yeast microsomes and rat liver microsomes with probe substrates.
The of ROS increased from 2.14 ± 0.38 (control) to 2.79 ± 0.37 (100 mg/kg) and 3.26 ± 1.08 h (200 mg/kg) in the single-dose GLT administration. The AUC (139.69 ± 45.46 vs. 84.58 ± 39.87 vs. 66.60 ± 15.90 h·μg/mL) and (2.75 ± 0.70 vs. 1.99 ± 0.44 vs. 1.68 ± 0.35 h) decreased significantly after multiple-dose GLT treatment. The IC values of quercetin, kaempferol, and isorhamnetin, GLT main constituents, were 9.32, 7.67, and 11.90 μmol/L for CYP2C8, and 27.31, 7.57, and 4.59 μmol/L for CYP2C9. The multiple-dose GLT increased rat CYP2C8 activity by 44% and 88%, respectively.
The metabolism of ROS is attenuated in the single dose of GLT by inhibiting CYP2C8 and CYP2C9 activity, and accelerated after the multiple-dose GLT treatment via inducing CYP2C8 activity in rats, indicating that the clinical dose of ROS should be adjusted when co-administrated with GLT.
银杏叶片剂（GLT）是一种传统的中草药配方，常用于治疗 2 型糖尿病，常与罗格列酮（ROS）联合使用。然而，GLT 和 ROS 之间的药物相互作用尚不清楚。
研究 GLT 对 ROS 药代动力学的影响及其潜在机制。
在 Sprague-Dawley 大鼠中研究了 10mg/kg ROS 与单剂量 100/200mg/kg GLT 和 10 天多次剂量给药的药代动力学。使用探针底物在重组人酵母微粒体和大鼠肝微粒体中测定 GLT 对 CYP2C8 和 CYP2C9 活性的影响。
单次 GLT 给药时，ROS 的 Cmax 从（对照）2.14±0.38 增加到 2.79±0.37（100mg/kg）和 3.26±1.08h（200mg/kg）。AUC（139.69±45.46 vs. 84.58±39.87 vs. 66.60±15.90h·μg/mL）和 Cmin（2.75±0.70 vs. 1.99±0.44 vs. 1.68±0.35h）在多次 GLT 治疗后显著降低。GLT 主要成分槲皮素、山柰酚和异鼠李素对 CYP2C8 的 IC 值分别为 9.32、7.67 和 11.90μmol/L，对 CYP2C9 的 IC 值分别为 27.31、7.57 和 4.59μmol/L。多次 GLT 分别使大鼠 CYP2C8 活性增加 44%和 88%。
GLT 单剂量抑制 CYP2C8 和 CYP2C9 活性，使 ROS 代谢减弱，多次 GLT 治疗后通过诱导大鼠 CYP2C8 活性加速 ROS 代谢，提示临床 ROS 剂量应与 GLT 联合使用时进行调整。
