Herbal medicine Yin Zhi Huang induces CYP3A4-mediated sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole
Herbal medicine Yin Zhi Huang induces CYP3A4-mediated sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole
复制标题
草药茵栀黄诱导 CYP3A4 介导的奥美拉唑磺化氧化和 CYP2C19 依赖性羟基化
DOI：
10.1111/j.1745-7254.2007.00617.x
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发表时间：
2007-10-01
影响因子：
8.2
通讯作者：
Hong-hao Zhou
中科院分区：
文献类型：
--
作者：
Fan, Lan;Guo Wang;Hong-hao Zhou
目的：探讨茵栀黄与CYP 3A 4和CYP 2C 19的底物奥美拉唑之间的相互作用。方法：18名健康志愿者，包括6名CYP 2C 19 *1/*1，6名CYP 2C 19 *1/*2或 *3，6名CYP 2C 19 *2/*2。每个阶段分别给予安慰剂或益脂口服液10 mL，每日3次，共14 d。然后所有患者口服奥美拉唑胶囊20 mg。在奥美拉唑给药后12 h内采集血样。结果：YZH治疗14 d后，奥美拉唑血药浓度显著降低，奥美拉唑砜和5-羟基奥美拉唑血药浓度显著升高。奥美拉唑与5-羟基奥美拉唑和奥美拉唑与奥美拉唑砜的0-无穷大血药浓度-时间曲线下面积（AUC（0-∞））比值下降64.80%±12.51%（P=0.001）和63.31%±18.45% CYP2C19*1/*1，57.98%±14.80%（P=0.004）CYP 2C 19 *1/*2或 *3分别为37.74% ±16.07%（P = 0.004）和45.16%±15.54%（P=0.003）。CYP 2C 19 *1/*1和CYP 2C 19 * 1/*2或 *3中奥美拉唑与5-羟基奥美拉唑的AUC（0-∞）比值的降低幅度大于CYP 2C 19 *2/*2中的AUC（0-∞）比值的降低幅度（P=0.047和P=0.009）。
AbstractAim:To explore the potential interactions between Yin Zhi Huang (YZH) and omeprazole, a substrate of CYP3A4 and CYP2C19.Methods:Eighteen healthy volunteers, including 6 CYP2C19*1/*1, 6 CYP2C19*1/*2 or *3 and 6 CYP2C19*2/*2 were enrolled in a 2-phase, randomized, crossover clinical trial. In each phase, the volunteers received either placebo or 10 mL YZH oral liquid, 3 times daily for 14 d. Then all the patients took a 20 mg omeprazole capsule orally. Blood samples were collected up to 12 h after omeprazole administration. Plasma concentrations of omeprazole and its metabolites were quantified by HPLC with UV detection.Results:After 14 d of treatment of YZH, plasma omeprazole significantly decreased and those of omeprazole sulfone and 5-hydroxyomeprazole significantly increased. The ratios of the area under the plasma concentration-time curves from time 0 to infinity (AUC(0-∞) of omeprazole to 5-hydroxyomprazole and those of omeprazole to omeprazole sulfone decreased by 64.80%±12.51% (P=0.001) and 63.31%±18.45% (P=0.004) in CYP2C19*1/*1, 57.98%±14.80% (P=0.002) and 54.87%±18.42% (P =0.003) in CYP2C19*1/*2 or *3, and 37.74%±16.07% (P=0.004) and 45.16%±15.54% (P=0.003) in CYP2C19*2/*2, respectively. The decrease of the AUC(0-∞) ratio of omeprazole to 5-hydroxyomprazole in CYP2C19*1/*1 and CYP2C19*1/*2 or *3 was greater than those in CYP2C19*2/*2 (P=0.047 and P=0.009).Conclusion:YZH induces both CYP3A4-catalyzed sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole leading to decreases in plasma omeprazole concentrations.