The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, P. R. China.
The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, P. R. China.
PLoS One. 2023 Aug 3;18(8):e0289656. doi: 10.1371/journal.pone.0289656. eCollection 2023.
The objection of this study was to investigate the effects of vindoline(VDL) on the cytochrome P450 (CYP 450) isoforms (CYP1A2, 2B, 2C11, 2D1 and 3A) in rats. Firstly, the rats were randomly divided into VDL pretreatment group and blank group, each group had six rats. VDL pretreatment group was administrated VDL (20 mg·kg-1) by oral gavage for fifteen days consecutively, and the equivalent CMC-Na solution without VDL was given to the blank group by gavage. Secondly, a cocktail of caffeine, bupropion, diclofenac, dextromethorphan and midazolam was then administered on the sixteenth day. Finally, blood samples were collected at the specified time point, and the plasma concentration of the probe drug was determined by UHPLC-QTOF-MS/MS. The effects of VDL on the activity of these CYP enzymes in rats were evaluated by pharmacokinetic parameters. VDL pretreatment group compared with the blank group, accelerated the metabolism of diclofenac, and weakened the metabolism of caffeine. These results suggested that VDL could induce the activity of CYP2C11, and inhibits the activity of CYP1A2, but had no significant effects on CYP2B, CYP2D1 and CYP3A. The results in this study can provide beneficial information for the later clinical application of VDL.
本研究旨在探讨文多灵（VDL）对大鼠细胞色素 P450（CYP）同工酶（CYP1A2、2B、2C11、2D1 和 3A）的影响。首先，将大鼠随机分为 VDL 预处理组和空白组，每组 6 只。VDL 预处理组连续 15 天经口给予 VDL（20mg·kg-1），空白组给予等体积的不含 VDL 的 CMC-Na 溶液。其次，在第 16 天给予包含咖啡因、安非他酮、双氯芬酸、右美沙芬和咪达唑仑的鸡尾酒探针药物。最后，在指定时间点采集血样，采用 UHPLC-QTOF-MS/MS 测定探针药物的血浆浓度。通过药代动力学参数评估 VDL 对这些 CYP 酶在大鼠体内活性的影响。与空白组相比，VDL 预处理组加速了双氯芬酸的代谢，减弱了咖啡因的代谢。这些结果表明，VDL 可以诱导 CYP2C11 的活性，抑制 CYP1A2 的活性，但对 CYP2B、CYP2D1 和 CYP3A 没有显著影响。本研究结果可为 VDL 的后期临床应用提供有益信息。
