Participation of P-glycoprotein in the central pharmacokinetics of phenytoin in an experimental model of epilepsy.

C HÖCHT; A LAZAROWSKI; N GONZÁLEZ; J AUZMENDI; JAW OPEZZO; GF BRAMUGLIA; CA TAIRA; GIRARDI E.

Cordoba

Congreso; XXXVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2006

Sociedad Argentina de Farmacología Experimental.

The present work examines the participation of the P-glycoprotein (P-gp) in the central pharmacokinetics of phenytoin (PHT) in an experimental model of epilepsy induced by 3-mercaptopropionic acid (MP). Seizures were induced in Wistar rats by injection of MP during 10 days. Control rats (C) were injected with saline solution (SS). A shunt or concentric microdialysis probe was inserted into the carotid artery or the hippocampus, respectively, in order to monitor PHT levels. PHT (30 mg.kg-1, i.v.) was injected 30 min after administration of vehicle (V) or nimodipine (NIMO, 2 mg.kg-1, ip). No differences were found in PHT plasma levels comparing all groups. In rats pretreated with V, hippocampal PHT levels were lower in MP rats (maximal concentration (Cmax): 2.7±0.3 µg/ml, p