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Antiepileptic drugs: Energy-consuming processes governing drug disposition
Pietro Fagiolino1,*,Marta Vazquez1,Silvana Alvariza1,Cecilia Maldonado1,Manuel Ibarra1,Ivette Olano1
1
Pharmaceutical Sciences Department. Faculty of Chemistry, Universidad de la Republica, P.O.Box 1157, 11800 Montevideo, Uruguay
DOI: 10.2741/E714 Volume 6 Issue 2, pp.387-396
Published: 01 June 2014
(This article belongs to the Special Issue Current advances in epilepsy and neurodegeneration)
*Corresponding Author(s):  
Pietro Fagiolino
E-mail:  
pfagioli@fq.edu.uy
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.

Key words

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

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Pietro Fagiolino, Marta Vazquez, Silvana Alvariza, Cecilia Maldonado, Manuel Ibarra, Ivette Olano. Antiepileptic drugs: Energy-consuming processes governing drug disposition. Frontiers in Bioscience-Elite. 2014. 6(2); 387-396.