title: 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.
authors.affiliation: Pharmaceutical Sciences Department, Faculty of Chemistry, Universidad de la Republica. P.O.Box 1157, 11800 Montevideo, Uruguay.
authors.forename: Pietro
authors.initials: P
authors.lastname: Fagiolino
authors.affiliation: Pharmaceutical Sciences Department, Faculty of Chemistry, Universidad de la Republica. P.O.Box 1157, 11800 Montevideo, Uruguay.
authors.forename: Marta
authors.initials: M
authors.lastname: Vazquez
authors.affiliation: Pharmaceutical Sciences Department, Faculty of Chemistry, Universidad de la Republica. P.O.Box 1157, 11800 Montevideo, Uruguay.
authors.forename: Silvana
authors.initials: S
authors.lastname: Alvariza
authors.affiliation: Pharmaceutical Sciences Department, Faculty of Chemistry, Universidad de la Republica. P.O.Box 1157, 11800 Montevideo, Uruguay.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Maldonado
authors.affiliation: Pharmaceutical Sciences Department, Faculty of Chemistry, Universidad de la Republica. P.O.Box 1157, 11800 Montevideo, Uruguay.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ibarra
authors.affiliation: Pharmaceutical Sciences Department, Faculty of Chemistry, Universidad de la Republica. P.O.Box 1157, 11800 Montevideo, Uruguay.
authors.forename: Ivette
authors.initials: I
authors.lastname: Olano
mesh_terms: D000927:Anticonvulsants / Q000378:metabolism* / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000502:physiology; D002220:Carbamazepine / Q000378:metabolism; D002302:Cardiac Output / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D049990:Membrane Transport Modulators / Q000378:metabolism*; D010672:Phenytoin / Q000378:metabolism / Q000493:pharmacokinetics; D014635:Valproic Acid / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000927:Anticonvulsants; D049990:Membrane Transport Modulators; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin