甘草酸对人体 CYP3A 酶活性的影响。
Effect of glycyrrhizin on the activity of CYP3A enzyme in humans.
机构信息
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, 110 Xiang-Ya Road, Changsha, Hunan 410078, People's Republic of China
出版信息
Eur J Clin Pharmacol. 2010 Aug;66(8):805-810. doi: 10.1007/s00228-010-0814-5. Epub 2010 Apr 15.
BACKGROUND
Glycyrrhizin is a major ingredient of licorice which is widely used in the treatment of various diseases such as chronic hepatitis. Licorice or glycyrrhizin has been shown to alter the activity of CYP3A in rodents. The influence of glycyrrhizin on CYP3A has not been elucidated in humans.
OBJECTIVE
To investigate the effects of repeated glycyrrhizin ingestion on the oral pharmacokinetics of midazolam, a probe drug for CYP3A activity in humans.
METHODS
Sixteen healthy adult male subjects were enrolled in a two-phase randomized crossover design. In each phase the volunteers received placebo or glycyrrhizin for 14 days. On the 15th day, midazolam was administered and blood samples were obtained to determine midazolam plasma concentrations. Bioequivalence was assessed by determining geometric mean ratios (GMRs) and 90% confidence intervals (90% CI).
RESULTS
The geometric mean (geometric coefficient of variation) for the AUC(0-infinity) of midazolam in the placebo group was 196.4 ng x h/ml (30.3%) and after glycyrrhizin treatment, 151.3 ng x h/ml (34.7%). The GMRs and 90% CI for AUC(0-infinity) and Cmax of midazolam in the presence/ absence of glycyrrhizin were 0.77 (0.70, 0.89) and 0.83 (0.74, 1.01), respectively. The 90% CI for AUC(0-infinity) and Cmax for the GMR of glycyrrhizin over placebo were both out of the no-effect boundaries of 0.80-1.25.
CONCLUSIONS
Administration of glycyrrhizin resulted in a modest induction of CYP3A that was clinically relevant according to the bioequivalence analysis.
背景
甘草酸是甘草的主要成分，广泛用于治疗慢性肝炎等各种疾病。甘草或甘草酸已被证明会改变啮齿动物 CYP3A 的活性。甘草酸对 CYP3A 的影响在人类中尚未阐明。
目的
研究重复摄入甘草酸对人体 CYP3A 活性探针药物咪达唑仑口服药代动力学的影响。
方法
16 名健康成年男性志愿者参加了一项两阶段随机交叉设计研究。在每个阶段，志愿者接受安慰剂或甘草酸治疗 14 天。第 15 天，给予咪达唑仑，并采集血样以测定咪达唑仑的血浆浓度。通过确定几何均数比值（GMR）和 90%置信区间（90%CI）来评估生物等效性。
结果
安慰剂组咪达唑仑 AUC（0-无穷大）的几何平均值（几何变异系数）为 196.4ng·h/ml（30.3%），而在甘草酸治疗后为 151.3ng·h/ml（34.7%）。咪达唑仑 AUC（0-无穷大）和 Cmax 存在/不存在甘草酸时的 GMR 及其 90%CI 分别为 0.77（0.70，0.89）和 0.83（0.74，1.01）。甘草酸相对于安慰剂的 AUC（0-无穷大）和 Cmax 的 GMR 的 90%CI 均超出 0.80-1.25 的无效应边界。
结论
甘草酸的给药导致 CYP3A 适度诱导，根据生物等效性分析，这与临床相关。
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