Zhang Yaqing, Zhang Zunjian, Song Rui
Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, 24 Tongjia lane, Nanjing, 210009, China.
State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing, 210009, China.
Eur J Drug Metab Pharmacokinet. 2018 Jun;43(3):291-300. doi: 10.1007/s13318-017-0444-8.
Rhubarb-Radix scutellariae is a classic herb pair, which is commonly used to clear away heat and toxin in clinic. The aim of this study was to investigate the influence of compatibility of Rhubarb and Radix scutellariae on the pharmacokinetic behaviors of anthraquinones and flavonoids in rat plasma.
Eighteen rats were randomly divided into three groups, and were orally administered Rhubarb and/or Radix scutellariae extracts. A sensitive and rapid UPLC-MS/MS method was developed and validated to determine the concentrations of baicalin, baicalein, wogonside, wogonin, rhein, and emodin in rat plasma. The concentrations of phase II conjugates of flavonoid aglycones and anthraquinone aglycones were also determined after hydrolyzing the plasma with sulfatase.
Compared with administration of Radix scutellariae alone, co-administration of Rhubarb significantly decreased the first maximum plasma concentration (C ) of baicalin, wogonside, and the phase II conjugates of baicalein, wogonin to 46.40, 61.27, 41.49, and 20.50%, respectively. The area under the plasma concentration-time curve from time zero to infinity (AUC) was significantly decreased from 82.60 ± 20.22 to 51.91 ± 7.46 μM·h for rhein and 276.83 ± 98.02 to 175.42 ± 86.82 μM·h for the phase II conjugates of wogonin after compatibility. The time to reach the first maximum plasma concentration (T ) of anthraquinones was shortened and the second peak of anthraquinones disappeared after compatibility.
Compatibility of Rhubarb and Radix scutellariae can significantly affect the pharmacokinetic behaviors of characteristic constituents of the two herbs. The cause of these pharmacokinetic differences was further discussed combined with the in vivo ADME (absorption, disposition, metabolism, and excretion) processes of anthraquinones and flavonoids.
大黄 - 黄芩是经典药对，临床常用于清热解毒。本研究旨在考察大黄与黄芩配伍对大鼠血浆中蒽醌类和黄酮类成分药代动力学行为的影响。
将18只大鼠随机分为3组，分别灌胃给予大黄和/或黄芩提取物。建立并验证了一种灵敏、快速的超高效液相色谱串联质谱（UPLC-MS/MS）方法，用于测定大鼠血浆中黄芩苷、黄芩素、汉黄芩苷、汉黄芩素、大黄酸和大黄素的浓度。在用硫酸酯酶水解血浆后，还测定了黄酮苷元和蒽醌苷元的Ⅱ相缀合物浓度。
与单独给予黄芩相比，大黄与黄芩配伍后，黄芩苷、汉黄芩苷以及黄芩素、汉黄芩素的Ⅱ相缀合物的血浆第一峰浓度（C ）分别显著降低至46.40%、61.27%、41.49%和20.50%。配伍后，大黄酸的血浆浓度 - 时间曲线下面积（AUC）从82.60±20.22显著降至51.91±7.46 μM·h，汉黄芩素Ⅱ相缀合物的AUC从276.83±98.02显著降至175.42±86.82 μM·h。配伍后，蒽醌类成分达到血浆第一峰浓度的时间（T ）缩短，且蒽醌类成分的第二个峰消失。
大黄与黄芩配伍可显著影响两药特征成分的药代动力学行为。结合蒽醌类和黄酮类成分的体内吸收、分布、代谢和排泄（ADME）过程，对这些药代动力学差异的原因进行了进一步讨论。
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