Zheng Xiang, Wen Jian, Liu Teng-Hui, Ou-Yang Qiu-Geng, Cai Jian-Ping, Zhou Hong-Yu
School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Biochem Res Int. 2017;2017:6510232. doi: 10.1155/2017/6510232. Epub 2017 Dec 4.
To discuss the effects of genistein on the metabolism of celecoxib in vitro and in vivo.
In vitro, the effects of genistein on the metabolism of celecoxib were studied using rat and human liver microsomes. In vivo, pharmacokinetics of celecoxib was evaluated in rats with or without genistein. Fifteen Sprague-Dawley (SD) rats were randomized into three groups: celecoxib (A group), celecoxib and 50 mg/kg genistein (B group), and celecoxib and 100 mg/kg genistein (C group). Single dose of 33.3 mg/kg celecoxib was orally administered 30 min after genistein ig. At 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after celecoxib administration, 300-400 µl blood samples were collected and the concentration of celecoxib was analyzed by ultrahigh-performance liquid chromatography-tandem mass spectrometry system.
Genistein showed notable inhibitory effects on three microsomes. It affected pharmacokinetics of celecoxib in vivo experiments. Genistein had dramatically ability to suppress CYP2C9∗1 and ∗3. After pretreatment with genistein, AUC and of the C group were higher than B group. CL/F of C group was lower than the B group.
Genistein inhibits the conversion of celecoxib in vitro and in vivo. So, the dosage of celecoxib should be adjusted if it was used associated with genistein.
探讨染料木黄酮对塞来昔布体内外代谢的影响。
体外实验中，采用大鼠和人肝微粒体研究染料木黄酮对塞来昔布代谢的影响。体内实验中，对给予或未给予染料木黄酮的大鼠进行塞来昔布的药代动力学评估。将15只Sprague-Dawley（SD）大鼠随机分为三组：塞来昔布组（A组）、塞来昔布+50mg/kg染料木黄酮组（B组）和塞来昔布+100mg/kg染料木黄酮组（C组）。在染料木黄酮灌胃30分钟后，口服单剂量33.3mg/kg塞来昔布。在给予塞来昔布后0.5、1、2、3、4、6、8、10、12和24小时，采集300 - 400μl血样，采用超高效液相色谱-串联质谱系统分析塞来昔布浓度。
染料木黄酮对三种微粒体均有显著抑制作用。在体内实验中，其影响了塞来昔布的药代动力学。染料木黄酮具有显著抑制CYP2C9∗1和∗3的能力。经染料木黄酮预处理后，C组的AUC和 高于B组。C组的CL/F低于B组。
染料木黄酮在体内外均抑制塞来昔布的转化。因此，塞来昔布与染料木黄酮联用时，应调整其剂量。
