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Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
Clopidogrel variability: role of plasma protein binding alterations
Shobana Ganesan1, Craig Williams, Cheryl L Maslen
1Department of Pharmacy Practice, College of Pharmacy, Oregon State University/Oregon Health & Science University, Portland, OR 97239, USA.
British Journal of Clinical Pharmacology
|November 3, 2012
Summary
The inactive metabolite of clopidogrel may increase the active metabolite's concentration, enhancing platelet inhibition. This finding offers a new strategy for optimizing clopidogrel therapy.
Area of Science:
- Pharmacology
- Clinical Chemistry
Background:
- Clopidogrel response variability is linked to pharmacokinetics.
- The pharmacokinetic behavior of clopidogrel and its metabolites is not fully understood.
- Inter-individual differences in clopidogrel response are multifactorial, involving genetic and non-genetic factors.
Purpose of the Study:
- To investigate if the inactive clopidogrel metabolite affects the plasma protein binding of the active metabolite.
- To explore the role of metabolite interactions in explaining clopidogrel response variability.
Main Methods:
- 28 female subjects with stable coronary disease were enrolled.
- Blood samples were collected after a 300 mg oral dose of clopidogrel.
- Plasma concentrations of active and inactive metabolites and platelet aggregation (VASP assay) were measured.
Main Results:
- A significant correlation was found between VASP assay results and both free and total concentrations of the active metabolite.
- Significant correlations were also observed between VASP assay results and both free and total concentrations of the inactive metabolite.
- Increasing protein binding of the inactive metabolite correlated with increased free fractions of the active metabolite.
Conclusions:
- In vivo data suggest the inactive metabolite displaces the active metabolite from plasma protein binding sites.
- This displacement may increase the free concentration of the active metabolite, enhancing platelet inhibition.
- Plasma protein binding interactions present a potential therapeutic strategy for optimizing clopidogrel pharmacotherapy.
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