Yu Zhenyan, Hu Xiaohan, Zhou Lin, Chen Huliang, Xing Yanchao, Han Chunyue, Ding Hui, Han Lifeng, Pan Guixiang, Fu Zhifei
State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Front Pharmacol. 2022 Jul 19;13:932646. doi: 10.3389/fphar.2022.932646. eCollection 2022.
Ginkgo Amillaria oral solution (GAO) is commonly used for the treatment of cardiovascular and cerebrovascular diseases in China. Piceatannol-3'---D-glucopyranoside for injection (PGI) is mainly used for the prevention and treatment of ischemic cerebrovascular diseases. With the spread of cerebrovascular disease, the possibility of combining the two drugs has increased; however, there is no research on the drug-drug interaction (DDI) between these two medicines. In this paper, an ultrahigh-performance liquid chromatography/quadrupole-orbitrap mass spectrometry (UHPLC/Q-Orbitrap MS) method was established to characterize the chemical constituents of GAO first; 62 compounds were identified or tentatively identified based on their retention time (RT), MS, and MS/MS data. Nine main compounds were determined by ultrahigh-performance liquid chromatography/triple quadrupole mass spectrometry (UPLC-QQQ-MS). Furthermore, incubation with liver microsomes was fulfilled; the results showed that GAO had a significant inhibitory effect on UGT1A9 and UGT2B7 ( < 0.05), and PGI was mainly metabolized by UGT1A9. The identification results of metabolites of PGI showed that PGI mainly undergoes a phase II binding reaction mediated by UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) . Therefore, pharmacokinetic studies were performed to investigate the DDI between GAO and PGI. The results showed that the AUC ( < 0.05) and T ( < 0.05) of PGI were significantly increased when administered together with GAO, whereas the CL was significantly decreased ( < 0.05). The exploration of and experiments showed that there was a DDI between GAO and PGI.
银杏蜜环口服溶液(GAO)在中国常用于治疗心脑血管疾病。注射用白藜芦醇 - 3'-O-D-吡喃葡萄糖苷(PGI)主要用于缺血性脑血管疾病的防治。随着脑血管疾病的蔓延,两种药物联合使用的可能性增加;然而,关于这两种药物之间的药物相互作用(DDI)尚无研究。本文首先建立了超高效液相色谱/四极杆 - 轨道阱质谱(UHPLC/Q-Orbitrap MS)方法来表征GAO的化学成分;根据保留时间(RT)、质谱和串联质谱数据鉴定或初步鉴定了62种化合物。通过超高效液相色谱/三重四极杆质谱(UPLC-QQQ-MS)测定了9种主要化合物。此外,进行了与肝微粒体的孵育实验;结果表明,GAO对UGT1A9和UGT2B7有显著抑制作用(P<0.05),PGI主要由UGT1A9代谢。PGI代谢产物的鉴定结果表明,PGI主要经历由尿苷二磷酸葡萄糖醛酸基转移酶(UGT)和磺基转移酶(SULT)介导的Ⅱ相结合反应。因此,进行了药代动力学研究以考察GAO与PGI之间的DDI。结果表明,PGI与GAO合用时,其AUC(P<0.05)和T(P<0.05)显著增加,而CL显著降低(P<0.05)。体外和体内实验探索表明,GAO与PGI之间存在药物相互作用。