从分子极性表面积预测头孢菌素类药物的血浆蛋白结合率

目的:采用分子结构参数预测头孢菌素类药物的血浆蛋白结合率。方法:用半经验自洽场分子轨道AM1法得到药物分子的优化几何构型,用Monte Carlo法计算分子极性表面积,相关分析采用逐步多元回归分析法。结果:头孢菌素类药物的血浆蛋白结合率(fb)与分子量(MW)和氢键给体表面积(SH)具有良好的相关性,回归方程式为:fb=0.5057 2.861×10-3MW-0.1572SH 4.714×10-3SH2(n=22,r=0.9042)。结论:头孢菌素类药物的血浆蛋白结合率不仅与药物的脂溶性,而且还与形成氢键的能力密切相关。从药物的分子量和极性表面积可以预测头孢菌素类药物的血浆蛋白结合率。

Prediction of plasma protein binding of cephalosporins from polar molecular surface areas

OBJECTIVE: To predict the plasma protein binding rate of cephalosporins from their molecular structural parameters. METHODS: The minimum energy conformations of cephalosporins were obtained from the optimization of the standard molecular geometry with the semiempirical self-consistent field molecular orbital calculation AM1 method; Mont Carlo method was used to calculate the polar molecular surface areas; the stepwise multiple regression analysis was used to obtain the correlation equations. RESULTS: The plasma protein binding rate of cephalosporins (fb) was well correlated with their molecular weights (MW) and surface areas of hydrogen-bonding donors (SH). The regression equation was: fb=0.5057+2.861x10(-3) MW-0.1572SH+4.714x10(-3) SH2(n=22, r=0.9042). CONCLUSION: Plasma protein binding of cephalosporins is closely related with their lipophilicity and hydrogen- bonding potential. The plasma protein binding rate of cephalosporins can be predicted from their molecular weights and surface areas of hydrogen-bonding donors.