@article{Karaźniewicz-Łada_Danielak_Burchardt_Główka_2014, title={The influence of diabetic status on the pharmacokinetics of clopidogrel and its metabolites in patients suffered from cardiovascular diseases}, volume={83}, url={https://jms.ump.edu.pl/index.php/JMS/article/view/70}, DOI={10.20883/medical.e70}, abstractNote={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.<br />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. <br />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. <br />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.}, number={3}, journal={Journal of Medical Science}, author={Karaźniewicz-Łada, Marta and Danielak, Dorota and Burchardt, Paweł and Główka, Franciszek}, year={2014}, month={Sep.}, pages={215–221} }