Alkharfy Khalid, Jan Basit, Alotaibi Khalid, Alotaibi Ayedh, Alqahtani Saeed, Raish Mohammad, Ahmad Ajaz
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Curr Drug Metab. 2021;22(12):969-977. doi: 10.2174/1389200222666211029152151.
Herbs usually contain a mixture of biologically active constituents, which can interact with numerous prescribed drugs and alter their safety profiles.
The current investigation was aimed to evaluate the effect of commonly used herbal products including black seed (Nigella sativa), garden cress (Lepidium sativum), and fenugreek (Trigonella foenum-graecum) on the pharmacokinetics and pharmacodynamics of clopidogrel using a Wistar rat model.
A GC-MS analysis revealed the presence of several phytoconstitutents (polyphenols) in the extracts of black seed, garden cress, and fenugreek. These polyphenols have the potential to interfere with clopidogrel effect. Plasma concentrations of clopidogrel were measured at different time points in the absence and presence of the concurrent use of tested herbal products and the pharmacokinetic parameters were calculated. Bleeding time was measured in various groups as a measure of the antiplatelet effect of clopidogrel.
Area under the plasma concentration-time curves (AUC0-∞) of clopidogrel were 35.53 ±0.89 μg/mlh (p<0.05), 26.01 ±0.90 μg/ml*h (p>0.05) and 32.80 ±2.51 μg/mlh (p<0.05) in the black seed, garden cress and fenugreek group, respectively, compared with that of the control group (27.02 ±0.42 μg/ml*h). Treatment with black seed also caused an increase in clopidogrel Cmax by 31.52% (p<0.05) and with fenugreek by 21.42% (p<0.05); Cmax, did not changed with garden cress treatment (6.48 ±0.15 μg/ml versus 6.12 ±0.21 μg/ml, p>0.05). The pharmacodynamic evaluation of the antiplatelet effect of clopidogrel in the presence of herbal products treatment showed a significant prolongation in the bleeding time from a control baseline by ~22-26%, and by added ~8-12% in reference to clopidogrel therapeutic effect (p<0.05).
The concurrent use of black seed, fenugreek, or garden cress can alter the pharmacokinetics and pharmacodynamics of clopidogrel to varying degrees due to the presence of various bioactive polyphenols. This is probably due to changes in drug disposition and its antiplatelet action. Further confirmation can determine the clinical relevance of these observations and identify the exact constituents responsible for such activities.
草药通常含有多种生物活性成分的混合物，这些成分可与多种处方药相互作用并改变其安全性。
本研究旨在使用Wistar大鼠模型评估常用草药产品（包括黑种草（Nigella sativa）、独行菜（Lepidium sativum）和胡芦巴（Trigonella foenum - graecum））对氯吡格雷药代动力学和药效学的影响。
气相色谱 - 质谱分析显示黑种草、独行菜和胡芦巴提取物中存在几种植物成分（多酚）。这些多酚有可能干扰氯吡格雷的作用。在不存在和存在受试草药产品同时使用的情况下，在不同时间点测量氯吡格雷的血浆浓度，并计算药代动力学参数。测量各实验组的出血时间，作为氯吡格雷抗血小板作用的指标。
与对照组（27.02±0.42μg/mlh）相比，黑种草、独行菜和胡芦巴组氯吡格雷的血浆浓度 - 时间曲线下面积（AUC0 - ∞）分别为35.53±0.89μg/mlh（p<0.05）、26.01±0.90μg/mlh（p>0.05）和32.80±2.51μg/mlh（p<0.05）。黑种草治疗使氯吡格雷的Cmax增加31.52%（p<0.05），胡芦巴使Cmax增加21.42%（p<0.05）；独行菜治疗后Cmax未改变（6.48±0.15μg/ml对6.12±0.21μg/ml，p>0.05）。在草药产品治疗存在的情况下，对氯吡格雷抗血小板作用的药效学评估显示，出血时间较对照基线显著延长约22 - 26%，相对于氯吡格雷治疗效果额外延长约8 - 12%（p<0.05）。
由于存在各种生物活性多酚，同时使用黑种草、胡芦巴或独行菜可在不同程度上改变氯吡格雷的药代动力学和药效学。这可能是由于药物处置及其抗血小板作用的改变。进一步的证实可以确定这些观察结果的临床相关性，并确定负责此类活性的确切成分。
