Abstract：
This work investigated interactions ascribed to the administration of phytomedicines containing Valeriana officinalis and Piper methysticum with conventional drugs. The phytomedicines were characterized by HPLC and administered per os to male Wistar rats, either concomitantly or not with the CYP3A substrate midazolam. To distinguish between the presystemic or systemic effect, midazolam was given orally and intravenously. The effects on the P-gp substrate fexofenadine uptake by Caco-2 cells were examined. The valerenic acid content was 1.6 ± 0.1 mg per tablet, whereas kavain was 13.7 ± 0.3 mg/capsule. Valerian and kava-kava extracts increased the maximum plasma concentration (Cmax) of midazolam 2- and 4-fold compared to the control, respectively. The area under the plasma concentrations versus time curve (AUC(0-∞)) was enhanced from 994.3 ± 152.3 ng.h/mL (control) to 3041 ± 398 ng.h/mL (valerian) and 4139 ± 373 ng.h/mL (kava-kava). The half-life of midazolam was not affected. These changes were attributed to the inhibition of midazolam metabolism by the enteric CYP3A since the i. v. pharmacokinetic of midazolam remained unchanged. The kava-kava extract augmented the uptake of fexofenadine by 3.5-fold compared to the control. Although Valeriana increased the uptake of fexofenadine, it was not statistically significant to that of the control (12.5 ± 3.7 ng/mg protein vs. 5.4 ± 0.3 ng/mg protein, respectively). Therefore, phytomedicines containing V. officinalis or P. methysticum inhibited the intestinal metabolism of midazolam in rats. Conversely, the P-gp-mediated transport of fexofenadine was preferably affected by kava-kava.
摘要：
这项工作研究了归因于施用含有缬草和Pipermethysticum的植物药与常规药物的相互作用。植物药通过HPLC表征，并按操作系统给予雄性Wistar大鼠，与CYP3A底物咪达唑仑同时或不同时。为了区分前系统或全身效应，咪达唑仑口服和静脉注射。检查了Caco-2细胞对P-gp底物非索非那定吸收的影响。戊酸含量为每片1.6±0.1毫克,而kavain为13.7±0.3毫克/粒。与对照组相比，缬草和卡瓦-卡瓦提取物使咪达唑仑的最大血浆浓度（Cmax）增加了2倍和4倍，分别。血浆浓度对时间曲线下面积(AUC(0-∞))从994.3±152.3ng增加。h/mL(对照)至3041±398ng。h/mL（缬草）和4139±373ng。h/mL(卡瓦-卡瓦)。咪达唑仑的半衰期没有受到影响。这些变化归因于肠CYP3A对咪达唑仑代谢的抑制,因为咪达唑仑的i.v.药代动力学保持不变。与对照相比，卡瓦-卡瓦提取物使非索非那定的吸收增加了3.5倍。虽然缬草增加了非索非那定的摄取，与对照组相比，无统计学意义(12.5±3.7ng/mg蛋白与5.4±0.3ng/mg蛋白质，分别)。因此,含V.officinalis或P.metheticum的植物药抑制大鼠肠道代谢的咪达唑仑。相反，P-gp介导的非索非那定转运受到卡瓦-卡瓦的影响。
