LB30057, a Direct Thrombin Inhibitor, the Effect of Restenosis in Porcine Coronary Injury Model

ABSTRACT

BACKGROUND AND OBJECTIVES: In a previous study, LB30057 was found to inhibit smooth muscle cell proliferation in a dose dependent manner, and prolonged 1 4-day oral administration of LB30057 is effective in reducing the neointimal hyperplasia in a rat carotid balloon injury model. The prolonged administration of LB30057, an orally active direct thrombin inhibitor, was evaluated and found to be a potential inhibitor of restenosis in a porcine coronary injury model. MATERIALS AND METHODS: An oversized balloon injury and a stent injury were given to the right coronary artery and left anterior descending artery, respectively, in the porcine model. LB30057 (50mg/kg) or a placebo was administrated for 28 days, using an osmotic pump, starting 6 hours prior to the injury until sacrifice on the 28th day. The drug concentration and antithrombotic effects (aPTT, thrombin-anti thrombin complex levels) were measured, and a histo-morphometric analysis performed 28 days later. RESULTS: The drug concentrations were 271+/-1 24 and 67+/-52 ng/mL on days 1 and 28 after injury in the drug group. The TAT (thrombin-antithrombin complex) levels were significantly lower in the drug than the control group on the 2nd and 7th days after injury (p<0.05). There were no significant differences in the injury scores, and the luminal, intimal and medial areas between the two groups. CONCLUSION: Prolonged administration of LB30057, using an osmotic pump, was not effective in reducing the restenosis in our pig coronary injury model.