Comparative fasting bioavailability of two clopidogrel formulations in healthy Mediterranean volunteers: an in vitro–in vivo correlation

Abstract

ObjectiveThe aim of this study was to evaluate the bioequivalence of two drug products, generic clopidogrel bisulfate 75 mg film-coated tablets versus the reference Plavix® clopidogrel bisulfate 75 mg film-coated tablets.MethodsBioequivalence of tablets was tested by comparisons against the reference brand product in accordance with the requirements of the Declaration of Helsinki, the current Good Clinical Practice Guidelines, and the International Conference on Harmonization.ResultsThe relationship between concentration and peak area ratio was found to be linear within the range 24.500–1,836.600 pg/mL for clopidogrel. The correlation coefficient (r) was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between test and reference. The point estimates (ratios of geometric mean) were 104.122%, 104.184%, and 109.091% for areas under the plasma concentration–time curve (AUC) AUC0-last, AUC0-∞, and peak plasma concentration Cmax, respectively. These pharmacokinetic parameter values of clopidogrel and its main metabolite lie within the bioequivalence limit (80%–125%) specified by the US Food and Drug Administration and the European Medicines Agency.ConclusionThe tested drug product was bioequivalent to the reference drug under fasting conditions and had the same safety profile, which is important to achieve equivalent therapeutic effect with the reference.

Pharmacodynamics Effect of Methylprednisolone Tablets on the Serum Concentration of Annexin A1: In Vivo Comparative Study Between Generic and Innovator Drug

“…Similar results were also obtained by Cooper-Dehoff and Elliott who compared patent and generic drugs of some blood pressure lowering agents that included beta-blockers, diuretics, and calcium antagonists [10]. Some other studies on clopidogrel and candesartan tablets also reported bioequivalence between their patent and generic products [11,12].…”

Pharmacodynamics Effect of Methylprednisolone Tablets on the Serum Concentration of Annexin A1: In Vivo Comparative Study Between Generic and Innovator Drug

“…Similar results were also obtained by Cooper-Dehoff and Elliott who compared patent and generic drugs of some blood pressure lowering agents that included beta-blockers, diuretics, and calcium antagonists [10]. Some other studies on clopidogrel and candesartan tablets also reported bioequivalence between their patent and generic products [11,12]. Methylprednisolone (MP) is a corticosteroid anti-inflammatory drug classified to glucocorticoid.…”

Antiplatelet Therapy in Acute Coronary Syndrome

“…Clopidogrel, prasugrel and ticagrelor are all adenosine diphosphate (ADP) antagonists, a class of therapeutic agents that bind selectively to the P2Y 12 receptor to inhibit platelet function (see Figure 1 and Table 1). 23 The thienopyridine, ticlopidine was the first drug in this class but is seldom prescribed now, following reports of serious adverse reactions, in particular neutropaenia 24 and thrombotic thrombocytopaenic purpura. 25…”

“…It is administered orally and up to 85 % of the absorbed drug undergoes hepatic metabolism by carboxylesterases to form an inactive carboxylic acid derivative, clopidogrelic acid, whilst the remaining 15 % is metabolised into the active thiol product by cytochrome P450 isoenzymes. 23,26 Although clopidogrel has a relatively short half-life of 6 hours, 27 28 Variable responses to clopidogrel may additionally result from mutations in the ABCB1 gene that encodes the P-glycoprotein involved in clopidogrel absorption. 28 The standard dosing regime is a 300 mg loading dose and 75 mg daily maintenance dose.…”