IMR Press / FBE / Volume 6 / Issue 2 / DOI: 10.2741/E714

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Antiepileptic drugs: Energy-consuming processes governing drug disposition
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1 Pharmaceutical Sciences Department. Faculty of Chemistry, Universidad de la Republica, P.O.Box 1157, 11800 Montevideo, Uruguay

*Author to whom correspondence should be addressed.

Academic Editor: Antoni Camins

Front. Biosci. (Elite Ed) 2014, 6(2), 387–396; https://doi.org/10.2741/E714
Published: 1 June 2014
(This article belongs to the Special Issue Current advances in epilepsy and neurodegeneration)
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.

Keywords
Efflux transporter
Cardiac output distribution
Gastrointestinal-blood cycling
Phenytoin
Carbamazepine
Valproic acid
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