Title:Clopidogrel-herb Interactions: A Pharmacokinetic and Pharmacodynamic Assessment
in a Rat Model
Volume: 22
Issue: 12
Author(s): Khalid Alkharfy*, Basit Jan, Khalid Alotaibi, Ayedh Alotaibi, Saeed Alqahtani, Mohammad Raish and Ajaz Ahmad*
Affiliation:
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Keywords:
Clopidogrel, fenugreek, black seed, garden cress, interaction, disposition, platelet function.
Abstract:
Background: Herbs usually contain a mixture of biologically active constituents, which can interact with
numerous prescribed drugs and alter their safety profiles.
Objectives: 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.
Methods: 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.
Results: Area under the plasma concentration-time curves (AUC0-∞) of clopidogrel were 35.53 ±0.89 μg/ml*h
(p<0.05), 26.01 ±0.90 μg/ml*h (p>0.05) and 32.80 ±2.51 μg/ml*h (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).
Conclusion: 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.
