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KMID : 0368120050350010015
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Korean Circulation Journal
2005 Volume.35 No. 1 p.15 ~ p.21
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LB30057, a Direct Thrombin Inhibitor, the Effect of Restenosis in Porcine Coronary Injury Model
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유병수/Yoo BS
윤정환/윤경희/이상구/이승환/김장영/고지연/황성오/최경훈/Yoon JH/Yoon KH/Lee SK/Lee SH/Kim JY/Ko JY/Hwang SO/Choe KH
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Abstract
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Background and Objectives：In a previous study, LB30057 was found to inhibit smooth muscle cell proliferation in a dose dependent manner, and prolonged 14-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 (50 mg/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±124 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.
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KEYWORD
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