Background: Clopidogrel, a potent antiplatelet agent, reduces the risk for thrombotic events in patients with atherothrombotic diseases. Clopidogrel is marketed primarily as a bisulfate salt. A different salt preparation of clopidogrel, clopidogrel besylate, has been developed and might provide an additional treatment option for patients.
Objective: The aim of this study was to compare the pharmacokinetic, pharmacodynamic, and tolerability profiles of clopidogrel besylate with those of clopidogrel bisulfate to determine bioequivalence for the purposes of marketing approval.
Methods: A randomized, open-label, 2-period, single- and multiple-dose, comparative crossover study was conducted in healthy Korean male subjects. The subjects received either clopidogrel bisulfate or clopidogrel besylate as a single 300-mg oral loading dose (day 1) followed by a 75-mg/d (once daily) maintenance dose on days 2 to 6. After a 15-day washout period, subjects were administered the alternative salt preparation according to the same protocol. The plasma concentrations of clopidogrel and its primary metabolite (SR26334) were assessed using high-performance liquid chromatography/tandem mass spectrometry after administration of the loading dose. The platelet aggregation response to 10-mumol/L adenosine diphosphate was measured using turbidometric aggregometry during the single- and multiple-dosing periods and at steady state (day 6). Tolerability was monitored using physical examination, including vital sign measurements, and laboratory analysis.
Results: Forty-four subjects were enrolled and completed the study (mean [SD] age, 24.3 [2.7] years; weight, 70.0 [8.2] kg). The mean values for C(max), T(max), and AUC(0-t) with clopidogrel (parent drug) of clopidogrel besylate (5.2 ng/mL, 0.9 hour, and 10.1 ng/mL/h, respectively) were similar to those with clopidogrel bisulfate (5.4 ng/mL, 0.9 hour, and 10.3 ng/mL/h). The mean values for Cmax, AUC(0-t), and AUC(0-infinity) with the SR26334 of clopidogrel besylate (10.9 microg/mL, 38.8 microg/mL/h, and 43.0 microg/mL/h, respectively) were not significantly different from those with the SR26334 of clopidogrel bisulfate (11.9 microg/mL, 40.6 microg/mL/h, and 43.8 microg/mL/h). The mean values for maximal antiplatelet effect (Emax) and area under the time-effect curve (AUEC) with the 2 clopidogrel salt preparations were as follows: clopidogrel besylate, 58.8 h . % and 4299.1 h . % inhibition, respectively; and clopidogrel bisulfate, 61.7 h . % and 4406.9 h . % inhibition; these differences were not statistically significant. The 90% CIs for the ratios of the log-transformed C(max), AUC, E(max), and AUEC values were within the predetermined bioequivalence range of 80% to 125%. Three adverse events (6.8%) were reported during the study and included abdominal discomfort (1 subject [2.3%] in the group that received clopidogrel bisulfate), easy fatigability (1 subject [2.3%] immediately before administration of loading dose of clopidogrel besylate), and thrombocytopenia (1 subject [2.3%] in the group receiving the clopidogrel bisulfate). All adverse events were transient and mild.
Conclusions: In these healthy Korean male subjects, the differences in the pharmacokinetic and pharmacodynamic properties between the 2 clopidogrel salt preparations did not reach statistical significance and met the regulatory requirements for bioequivalence. Both preparations were well tolerated.
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http://dx.doi.org/10.1016/j.clinthera.2009.04.017 | DOI Listing |
In Tanzania, acute myocardial infarction (AMI) is under-diagnosed, and uptake of evidence-based care is sub-optimal. Using an implementation science approach, an intervention was developed to address local barriers to care: the Multicomponent Intervention for Improving Myocardial Infarction Care in Tanzania (MIMIC). This single-arm pre-post trial was conducted in a northern Tanzanian emergency department (ED).
View Article and Find Full Text PDFAm Heart J
December 2024
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Shanghai, China; Department of Cardiology, Shanghai Geriatric Medical Center, Shanghai, China. Electronic address:
Background: It remains unclear whether indobufen-based dual antiplatelet therapy (DAPT) preserves ischemic protection while limiting bleeding risk in patients with multivessel coronary disease (MVD). This study aimed to investigate the efficacy and safety of indobufen-based DAPT in patients with MVD.
Methods: Patients in the OPTION trial were stratified based on the presence of MVD.
Ann Thorac Surg
December 2024
Department of Thoracic and Cardiovascular Surgery, UT MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Electronic address:
Indian Heart J
December 2024
Apollo Institute of Medical Sciences and Research, Jubilee Hills, Film Nagar, Hyderabad, Telangana, 500090.
Introduction: Various cardiovascular thrombo-embolic clinical entities use combined ATS for prevention and treatment. After PCI, AF patients are typically prescribed DOAC, DAPT/SAPT, as component of ATS to minimize stroke risk and treat pulmonary embolism and venous thromboembolism. Some small observational studies have shown that a combined ATS can clear small thrombi in LV dysfunction and/or apical aneurysms.
View Article and Find Full Text PDFJ Evid Based Med
December 2024
Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, China.
Objective: The optimal low-dose antiplatelet agents in patients with coronary heart disease (CHD) had not been determined. The objective of this study was to compare the impact of different low-dose antiplatelet agents on cardiovascular outcomes and bleeding risks in patients with CHD.
Methods: We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, VIP, WanFang Data, and China Biology Medicine.
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