Antiepileptic drugs: Energy-consuming processes governing drug disposition.

Abstract

Diffusion is not the main process by which drugs are disposed throughout the body. Translational movements of solutes given by different energy-consuming mechanisms are required in order to dispose them efficiently. Membrane transportation and cardiac output distribution are two effective processes to move the molecules among different body sites. Gastrointestinal-blood cycling constitutes a supplementary way to regulate the distribution of molecules between the non-hepatic organs and the liver. Any change in the relative supply of drug molecules among eliminating organs could modify their clearance from the body. Either the nonlinear phenytoin (PHT) pharmacokinetic response or the influence that carbamazepine (CBZ) exerts on PHT exposure could be explained throughout their efflux transporter inducer abilities. Cardiac output distribution difference between the individuals might also explain the dual CBZ-over-PHT interaction response. Finally, valproic acid (VPA) pharmacokinetics can be understood by adding to these mechanisms of transportation its ability to cross the mitochondrial membrane of the hepatocyte.