Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
J Trace Elem Med Biol. 2018 Jul;48:81-86. doi: 10.1016/j.jtemb.2018.03.012. Epub 2018 Mar 14.
NiuHuangJieDu Tablets (NHJDT), a popular realgar (AsS) containing patented traditional Chinese medicine (TCM), is widely used in the treatment of acute tonsillitis, pharyngitis, periodontitis and mouth ulcer. However, arsenic is considered as one of the most toxic elements, leading to growing concerns about the quality and safety of realgar-containing TCMs recently. In this study, health risk assessment of arsenic in realgar and NHJDT was conducted through oral administration of both substances to rats with single and multiple doses, respectively. The total blood arsenic concentration was used as the health risk indicator and determined by hydride generation-atomic fluorescence spectrometry after modified Kjeldahl digestion, and then applied to the pharmacokinetic study. For single oral dose study in rats, the low, medium, and high doses of realgar and NHJDT were set equivalent to 1, 5 and 20 times the human therapeutic dose (1.3 mg realgar/kg), respectively. Multiple doses were given at low and high dose levels every 12 h for seven consecutive days, respectively. Significant differences in the total blood arsenic pharmacokinetic profiles were observed between the corresponding realgar and NHJDT groups. These results indicated that NHJDT significantly reduced the total blood arsenic exposure present in realgar, and the detoxification mechanism might be attributed to herb-herb interactions in NHJDT. However, the accumulation of blood total arsenic was significant due to the long elimination half-life and high accumulation index in both realgar and NHJDT groups. Therefore, the potential health risk of arsenic caused by the administration of realgar-containing TCMs should be taken into account for excessive or long-term medication. Precautions should be taken for the clinical application of realgar-containing TCMs.
牛黄解毒片（NHJDT）是一种含雄黄（AsS）的专利中药，广泛用于治疗急性扁桃体炎、咽炎、牙周炎和口腔溃疡。然而，砷被认为是毒性最大的元素之一，最近人们对含雄黄的中药的质量和安全性越来越关注。本研究采用雄黄和 NHJDT 分别对大鼠进行单次和多次灌胃，通过测定总血砷浓度，对砷的健康风险进行评估。总血砷浓度作为健康风险指标，采用改良凯氏消解-氢化物发生原子荧光光谱法测定，并应用于药代动力学研究。大鼠单次灌胃研究中，雄黄和 NHJDT 的低、中、高剂量分别相当于人体治疗剂量（1.3mg 雄黄/kg）的 1、5 和 20 倍。连续 7 天，低、高剂量组分别以低、高剂量每隔 12h 给药 1 次。结果表明，雄黄和 NHJDT 组的总血砷药代动力学特征存在显著差异。这表明 NHJDT 可显著降低雄黄引起的总血砷暴露，解毒机制可能与 NHJDT 中的药-药相互作用有关。然而，由于雄黄和 NHJDT 组的消除半衰期长、蓄积指数高，导致血液总砷的蓄积明显。因此，含雄黄的中药长期或过量用药可能会导致砷的健康风险，在临床应用中应引起重视。
