[Prediction of plasma protein binding of cephalosporins from polar molecular surface areas].

Zhejiang Da Xue Xue Bao Yi Xue Ban

Department of Pharmacy, Zhejiang University City College, Hangzhou 310015, China.

Published: July 2007

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.

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http://dx.doi.org/10.3785/j.issn.1008-9292.2007.04.014DOI Listing

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