Pre-Clinical and Phase I Clinical Study of Clopidogrel Lipid Suspension: Intravenously Injected Formulation Results in Faster Onset of Action and Dose-Dependent Inhibition of Platelet Aggregation

Clopidogrel Lipid Suspension was formulated in lipid based aqueous system and characterized for morphology and particle size using physicochemical techniques. Transmission Electron Microscopy (TEM) cryo imaging analysis revealed the presence of predominantly spherical unilamellar liposome particles with 25-110 nm size and the product was found to be stable at 2-8°C for 2 years. Repeated dose toxicity study of Clopidogrel Lipid Suspension showed no signs of toxicity in rats and minimal toxicity in mice. Pharmacokinetic studies indicated a rapid metabolism of Clopidogrel following intravenous administration of Clopidogrel Lipid Suspension compared to oral administration of Clopidogrel bisulfate. Intravenous administration of 5, 10, 20, and 40 mg/kg Clopidogrel Lipid Suspension showed a dose dependent effect on the platelet aggregation in mice. An oral dose of 20 mg/kg of Clopidogrel was required to produce similar effects by intravenous administration of only 5 mg/kg in mice with Clopidogrel Lipid Suspension. Phase I clinical safety studies were also conducted in 48 healthy human subjects with dose escalation from 25 mg to 75 mg. All subjects who experienced adverse events during this study recovered completely and no serious adverse events were reported.