Formation of hydrogen-bonded complexes between bile acids and lidocaine in the lidocaine transfer from an aqueous phase to chloroform

Abstract

Bile acids are amphiphilic molecules, which, in addition to their physiological role, have also acquired increasingly more important pharmacological applications. It has been shown that these compounds have a promoting effect on the transport of many drugs through the cell membrane. Pharmacodynamic studies showed that they exerted a significant effect on the analgesic action of lidocaine. This study is concerned with the determination of the constants of hydrogen-bonded complexes formed between the investigated bile acids and lidocaine. It was found that a prerequisite for forming such a complex is the existence of at least two OH groups or one OH group and one keto group in the bile acid molecule at an appropriate mutual distance. If a keto group is involved in lidocaine binding, the resulting complex has a larger equilibrium constant. A model - multiple linear regression equation - was constructed, relating the molecular descriptors to the equilibrium constant of hydrogen-bonded complex. It was also shown how the complex formed between lidocaine and bile acid influences the rate constant of the decrease of lidocaine concentration in the aqueous phase during its transfer to the chloroform solution of a bile acid. It was found that the complex formed between lidocaine and bile acids plays an important role in the appearance of the depot effect of lidocaine. © 2008 Elsevier B.V. All rights reserved.