Prediction of plasma protein binding of cephalosporins from polar molecular surface areas / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To predict the plasma protein binding rate of cephalosporins from their molecular structural parameters.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>