Published: 2016-02-17

The influence of diabetic status on the pharmacokinetics of clopidogrel and its metabolites in patients suffered from cardiovascular diseases

Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poland
Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poland
Division of Cardiology-Intensive Therapy, Department of Internal Medicine Poznan University of Medical Sciences, Poland
Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poland
clopidogrel active metabolite diabetes mellitus platelet aggregation

Abstract

Aim. A significant percentage of individuals treated with an anti-platelet agent clopidogrel do not receive the expected therapeutic effect. Clopidogrel resistance is even more prevalent in patients with type 2 diabetes mellitus (DM). An extensive investigation on pharmacokinetics of clopidogrel and its metabolites in patients with type 2 DM suffering from cardiovascular diseases were performed following an administration of 75 mg of the drug.
Material and methods. Plasma concentrations of clopidogrel, its carboxylic metabolite (CLPM) and diastereoisomers of a thiol metabolite (the inactive H3 and the active H4) were determined by a validated HPLC-MS/MS method. The pharmacokinetic parameters of the analytes in diabetic (n = 16) and non-diabetic (n = 28) patients were compared and correlated with platelet aggregation.
Results. DM patients exhibited a slightly higher Cmax of clopidogrel (2.34 ± 2.29 ng/mL) compared with non-diabetic group (1.82 ± 1.86 ng/mL), whereas plasma levels of clopidogrel metabolites were lower in DM than in non-DM patients (2339 ± 989 ng/mL vs. 2662 ± 2090 ng/mL, 4.64 ± 4.79 ng/mL vs. 5.42 ± 4.55 ng/mL and 6.42 ± 4.80 ng/mL vs. 7.44 ± 7.18 ng/mL, respectively for CLPM, H3 and H4). A significant correlation was found between platelet aggregation and the Cmax of the active H4 metabolite in non-diabetic patients.
Conclusions. Pharmacokinetic parameters of clopidogrel, CLPM, H3 and H4 isomers in patients with DM did not differ significantly from those determined in non-diabetic group. Moreover, the antiplatelet response to clopidogrel therapy measured by ADP-stimulated platelet aggregation was similar in both groups of patients.

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How to Cite

1.
Karaźniewicz-Łada M, Danielak D, Burchardt P, Główka F. The influence of diabetic status on the pharmacokinetics of clopidogrel and its metabolites in patients suffered from cardiovascular diseases. JMS [Internet]. 2016Feb.17 [cited 2020Aug.5];83(3):215-21. Available from: https://jms.ump.edu.pl/index.php/JMS/article/view/70