Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
J Pharm Biomed Anal. 2013 Sep;83:179-85. doi: 10.1016/j.jpba.2013.05.003. Epub 2013 May 16.
The purpose of this study is to systematically investigate the pharmacokinetic (PK) behaviors of radix Sophorae tonkinensis (S. tonkinensis) using oxymatrine (OMT) and matrine (MT) as the target markers (2 mg/kg OMT and 1.3 mg/kg MT, oral administration). The PK characteristics in radix S. tonkinensis extracts were also compared with those of pure OMT. A fast ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed. OMT absorption was very fast, and no significant differences were observed (p>0.05) in tmax, CL, and t1/2 for both pure OMT and extracts. Cmax and AUC0→∞ of pure OMT were significantly higher than those of S. tonkinensis extracts (Cmax, 61.64±6.65 vs. 43.24±10.14 ng/mL; AUC, 9894.48±2234.99 vs. 4730.30±3503.8 min ng/mL) (p<0.05). However, the absolute OMT bioavailability of pure OMT was higher than that of the compound in radix S. tonkinensis extracts (6.79±2.52% vs. 1.87±2.66%). By contrast, the bioavailability of total alkaloids (OMT+MT) after pure OMT administration was 81.14±8.83%, similar to that of radix S. tonkinensis extracts (69.36±17.37%) (p>0.05). It was presumed that OMT absorption has no effect on the bioavailability of the two alkaloids. Other constituents in radix S. tonkinensis extracts can influence the transformation of OMT to MT, which directly leads to variations in the PK behavior of OMT. In addition, the protein binding of OMT and MT in plasma was very low (4.80%-8.95% for OMT, 5.10-10.55% for MT). In conclusion, OMT in radix S. tonkinensis extracts exhibits different PK behaviors with pure OMT through the transformation of OMT to MT due to other complex ingredients.
本研究旨在系统研究氧化苦参碱（OMT）和苦参碱（MT）作为目标标志物时，苦参的药代动力学（PK）行为（OMT 为 2mg/kg，MT 为 1.3mg/kg，口服给药）。还比较了苦参提取物中苦参 PK 特征与纯 OMT 的 PK 特征。建立了快速超高效液相色谱-串联质谱（UPLC-MS/MS）法。OMT 吸收非常快，纯 OMT 和提取物的 tmax、CL 和 t1/2 无显著差异（p>0.05）。纯 OMT 的 Cmax 和 AUC0→∞明显高于苦参提取物（Cmax，61.64±6.65 比 43.24±10.14ng/mL；AUC，9894.48±2234.99 比 4730.30±3503.8 minng/mL）（p<0.05）。然而，纯 OMT 的绝对 OMT 生物利用度高于苦参提取物中的化合物（6.79±2.52%比 1.87±2.66%）。相比之下，纯 OMT 给药后总生物碱（OMT+MT）的生物利用度为 81.14±8.83%，与苦参提取物相似（69.36±17.37%）（p>0.05）。推测 OMT 吸收对两种生物碱的生物利用度没有影响。苦参提取物中的其他成分可能会影响 OMT 向 MT 的转化，从而直接导致 OMT PK 行为的变化。此外，OMT 和 MT 在血浆中的蛋白结合非常低（OMT 为 4.80%-8.95%，MT 为 5.10-10.55%）。综上所述，由于其他复杂成分的存在，苦参提取物中的 OMT 表现出与纯 OMT 不同的 PK 行为，这是通过 OMT 向 MT 的转化实现的。
