title: The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part II: Pharmacological issues and further understanding.
abstract: The literature on inducers in epilepsy and bipolar disorder is seriously contaminated by false negative findings. Part II of this comprehensive review on antiepileptic drug (AED) inducers provides clinicians with further educational material about the complexity of interpreting AED drug-drug interactions. The basic pharmacology of induction is reviewed including the cytochrome P450 (CYP) isoenzymes, the Uridine Diphosphate Glucuronosyltransferases (UGTs), and P-glycoprotein (P-gp). CYP2B6 and CYP3A4 are very sensitive to induction. CYP1A2 is moderately sensitive while CYP2C9 and CYP2C19 are only mildly sensitive. CYP2D6 cannot be induced by medications. Induction of UGT and P-gp are poorly understood. The induction of metabolic enzymes such as CYPs and UGTs, and transporters such as P-gp, implies that the amount of these proteins increases when they are induced; this is almost always explained by increasing synthesis mediated by the so-called nuclear receptors (constitutive androstane, estrogen, glucocorticoid receptors and pregnaneX receptors). Although parti provides correction factors for AEDs, extrapolation from an average to an individual patient may be influenced by administration route, absence of metabolic enzyme for genetic reasons, and presence of inhibitors or other inducers. AED pharmacodynamic DDIs may also be important. Six patients with extreme sensitivity to AED inductive effects are described.
authors.affiliation: University of Kentucky Mental Health Research Center at Eastern State Hospital, Lexington, KY, Estados Unidos; Grupo de Investigación en Neurociencias (CTS-549), Instituto de Neurociencias, Universidad de Granada, Granada, España; Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Hospital Santiago Apóstol, Universidad del País Vasco, Vitoria, España. Electronic address: jdeleon@uky.edu.
authors.forename: Jose
authors.initials: J
authors.lastname: de Leon
mesh_terms: D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants
keywords: Anticonvulsants; Anticonvulsivos; Aryl hydrocarbon receptor; Constitutive androstane receptor; Estrogen receptors; Glucocorticoid receptor; Pregnane X receptor; Receptor constitutivo de androstano; Receptor de aril hidrocarburos; Receptor de los glucocorticoides; Receptor de pregnano X; Receptores de los estrógenos