Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
J Pharm Pharmacol. 2020 Jul;72(7):979-989. doi: 10.1111/jphp.13268. Epub 2020 Apr 13.
This study aimed to evaluate the inhibitory effects of Huosu Yangwei oral liquid (HSYW) on cytochrome P450 enzymes (CYPs) and to investigate whether this herbal medicine could modulate the pharmacokinetic behaviour of the co-administered CYP-substrate drug apatinib.
Cytochrome P450 enzymes inhibition assays were conducted in human liver microsomes (HLM) by a LC-MS/MS method for simultaneous determination of the oxidative metabolites of eight probe substrates for hepatic CYPs. The modulatory effects of HSYW on the oxidative metabolism of apatinib were investigated in both HLM and rat liver microsomes (RLM). The influences of HSYW on the pharmacokinetic behaviour of apatinib were investigated in rats.
Huosu Yangwei oral liquid inhibited all tested CYPs in human liver preparations, with the IC values ranged from 0.3148 to 2.642 mg/ml. HSYW could also inhibit the formation of two major oxidative metabolites of apatinib in liver microsomes from both human and rat. In-vivo assays demonstrated that HSYW could significantly prolong the plasma half-life of apatinib by 7.4-fold and increase the AUC (nm·h) of apatinib by 43%, when HSYW (10 ml/kg) was co-administered with apatinib (10 mg/kg) in rats.
Huosu Yangwei oral liquid could inhibit mammalian CYPs and modulated the metabolic half-life of apatinib both in vitro and in vivo.
本研究旨在评价和胃养阴口服液（HSYW）对细胞色素 P450 酶（CYPs）的抑制作用，并探讨该中药是否能调节合用的 CYP 底物药物阿帕替尼的药代动力学行为。
采用 LC-MS/MS 法在人肝微粒体（HLM）中进行细胞色素 P450 酶抑制试验，同时测定 8 种肝 CYP 探针底物的氧化代谢物。在 HLM 和大鼠肝微粒体（RLM）中研究了 HSYW 对阿帕替尼氧化代谢的调节作用。在大鼠中研究了 HSYW 对阿帕替尼药代动力学行为的影响。
和胃养阴口服液在人肝制剂中抑制所有测试的 CYP，IC 值范围为 0.3148-2.642mg/ml。HSYW 还可以抑制阿帕替尼在人源和大鼠源肝微粒体中的两种主要氧化代谢物的形成。体内试验表明，当 HSYW（10ml/kg）与阿帕替尼（10mg/kg）在大鼠中合用时，HSYW 可使阿帕替尼的血浆半衰期显著延长 7.4 倍，使阿帕替尼的 AUC（nm·h）增加 43%。
和胃养阴口服液可抑制哺乳动物 CYP，并在体外和体内调节阿帕替尼的代谢半衰期。
