The influence of physicochemical parameters on the biliary excretion of a series of nitroimidazoles.

Abstract

The relationship between physicochemical parameters and biliary excretion of nitroimidazoles was investigated. The unmetabolized form of each drug was detected in the bile by means of a UV procedure. A highly significant reversed parabolic relationship was shown between the Rm values and the biliary excretion of the test compounds. In other words, the compounds closer to the optimal Rm value are excreted less than those characterized by higher or lower Rm values. Since the Rm values seem to account for both the lipophilic and polar character of nitroimidazoles, the reversed parabola could be due to plasma protein binding and/or some protein binding within the hepatocyte. In fact, both the lipophilic and polar character seem to play an important role in protein binding of chemicals.