Quantitative structure property relationship studies for predicting plasma protein binding properties of Cephalosporins

Abstract

Cephalosporins are of key clinical importance for treatment of bacterial infections. In the past decade, many cephalosporins have been synthesized and evaluated for antibacterial activity. These cephalosporins, with broad spectra of activity and high stability against various β-lactamases such as cefixime, cefteram pivoxil, and cefpodoxime proxetil, have been developed and introduced in clinical practice. Efforts to synthesize more compounds for better activity are still on. It is very important that the antibiotic has favorable pharmacokinetic properties [absorption, distribution, metabolism, excretion (ADME)]. Hence, predicting pharmacokinetic parameters, of a new molecule, in an early stage of drug design, is of as high importance as the activity of the compound. With rapid advances in computation power of machines and availability of experimental data, these ADME properties can now be better predicted by using suitable computational methods. In present study, an attempt has been made to derive quantitative relationships between structure of cephalosporins and one of the important pharmacokinetic property, serum plasma protein binding.