摘要
目的:比较药物CPU86017及其手性化合物(7S,13R)-CPU86017对兔心肌缺血/再灌注损伤的保护作用和药动学差异。方法:30只新西兰白兔随机分为5组:假手术对照组(组1),缺血再灌注模型组(组2),阳性对照药普奈洛尔组(组3),CPU86017干预组(组4),(7S,13R)-CPU86017干预组(组5)。再灌注结束后取心脏测定梗死区心肌中LDH,GOT及CK的活力,并于给药后不同时间点取血,用HPLC法测CPU86017和(7S,13R)-CPU86017的血药浓度。结果:组1的GOT,CK和LDH活力分别为每毫克蛋白(689±54.3)U,每毫升蛋白(372.9±61.1)U和每克蛋白(62 696.4±478.4)U,组2的各项酶水平均较组1显著降低(P<0.01),心肌梗死损害明显。组4和组5的各酶水平显著提高(P<0.05),其中,(7S,13R)-CPU86017逆转梗死区心肌酶水平降低的作用要优于CPU86017(P<0.05)。兔腹腔注射CPU86017或(7S,13R)-CPU86017后,血药浓度按一房室模型拟合较佳。药动学研究表明,(7S,13R)-CPU86017比CPU86017具有更高的AUC。结论:对映体(7S,13R)-CPU86017比CPU86017具有更好的药理学和药动学特性。
Objective： To compare the effects of CPU86017 and its chiral compounds （7S, 13R）- CPU86017 on myocardial ishemia-reperfusion injury in rabbit heart and the differences on pharmacokinetics. Methods： Rabbits were randomly divided into 5 groups： sham group（group 1）, myocardial ischemia-reperfusion group （group 2）, propranolol group （group 3）, CPU86017 pretreatmaent group （group 4） and （7S, 13 R ）-CPU86017 pretreatrnent group（ group 5）. At the end of reperfusion, the levels of LDH, GOT and CK in the infarct area were measured. The plasma was collected at different time points after administration and plasma concentrations of drug were detected by HPLC. Results： Compared with group 1 [GOT： （689±54.3） U （in one milligram protein） ,CK： （372.9± 61.1）U/mL and LDH： （62 696.4 ± 478.4） U （in one gram protein） ], the levels of GOT, CK and LDH in group 2 decreased significantly （ P 〈 0.01 ）. Those levels in group 4 and group 5 were increased than those of group 2 （ P 〈 0.05）, which presented theraputical effects of two compounds on myocardial injury, and （7 S, 13 R ）-CPU86017 showed a better effect than that of CPU86017 （ P 〈 0.05）. The concentration-time curve of CPU86017 and（7 S, 13 R ）-CPU86017 were fit to one-compartment open model. Conclusion： （7 S, 13 R）-CPU86017 has a higher value than CPU86017 in pharmacology and pharmacokinetics.
出处
《药学进展》
CAS
2007年第1期26-31,共6页
Progress in Pharmaceutical Sciences
基金
国家自然科学基金资助项目(30572193)
江苏省自然科学基金资助项目(BK2002120)
