GIRARDI Elena Silvia
congresos y reuniones científicas
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, E, GIRARDI E.
Congreso; XXXVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2006
Sociedad Argentina de Farmacología Experimental (SAFE)
Participation of P-glycoprotein in the central pharmacokinetics of phenytoin in an experimental model of epilepsy. Höcht C, Lazarowski A, Gonzalez N, Auzmendi J, Opezzo J, Bramuglia G, Taira C, Girardi E .Cátedra de Farmacología, FFyB, UBA. 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<0.05 vs C) compared to C animals (Cmax: 5.3±0.9 µg/ml). Whilst pretreatment with NIMO did not modify central kinetics of PHT in C (Cmax: 4.5±0.8 µg/ml), PHT levels were significantly higher in MP rats pretreated with NIMO (Cmax: 6.8±1.0 µg/ml, p<0.05 vs MP rats pretreated with SS). Our results indicate that central pharmacokinetics of PHT is altered in MP induced epileptic rats. The effect of NIMO on hippocampal levels of PHT suggest that P-gp is implicated in the reduced central bioavailability of PHT in this experimental model of epilepsy.