Intravenous Clopidogrel (MDCO-157) Compared with Oral Clopidogrel: The Randomized Cross-Over AMPHORE Study

Background The extent of P2Y 12 inhibition during coronary intervention is an important determinant of ischemic complications. The currently available oral P2Y 12 inhibitors are limited by a relatively slow onset of action and variable on-treatment response. Objective Our objective was to determine the pharmacodynamic (PD) dose–antiplatelet response relationship and the pharmacokinetics of MDCO-157, an intravenous formulation of clopidogrel complexed with sulphobutylether betacyclodextrin, and to identify the dose level of MDCO-157 that matches the PD effect of oral clopidogrel 300 mg. Methodology A randomized open-label crossover study was performed in 33 healthy adult volunteers to determine the pharmacokinetic (clopidogrel and clopidogrel H4 thiol active metabolite) and the PD (vasodilator-stimulated phosphoprotein [VASP]) effects of MDCO-157 at doses of 75, 150, and 300 mg and of oral clopidogrel 300 mg. Results Data are presented as %, mean (standard deviation). The maximum effect of P2Y 12 receptor inhibition assessed by flow cytometry using VASP was 70.42 (6.7), 69.45 (7.1), and 65.58 (12.6) for intravenous MDCO-157 at doses of 75, 150, and 300 mg, respectively, compared with 56.6 (17.5) with oral clopidogrel 300 mg administration ( p