Abstracts

The present work addressed possible participation of the efflux transporter P-glycoprotein (P-gp) in the alterations of the central pharmacokinetics of phenytoin in an experimental model of epilepsy induced by the administration of mercaptopropionic acid., Male Wistar rats were administered for 7 days with physiological solution (SF) or mercaptopropionic (MP) acid. The day of the experiment, a shunt micrordialysis probe or a concentric probe was inserted into the carotid artery or the hippocampus respectively, in order to monitor extracellular phenytoin (PHT) levels. In SF and MP treated rats, PHT (30 mg/kg, i.v.) was administered 30 after an intraperitoneal administration of SF or nimodipine (NIMO, 2 mg/kg). Pharmacokinetic analysis of the data was made using TOPFIT program., No differences were found in PHT plasmatic levels comparing all experimental groups. In rats pretreated with SF, hipocampal PHT concentrations were signicantly lower in MP treated rats (maximal concentration (Cmax): 2.7[plusmn]0.3 [micro]g/ml, p[lt]0.05 vs SF rats) compared to SF animals (Cmax: 5.3[plusmn]0.9 [micro]g/ml). Whilst pretreatment with NIMO did not modify central pharmacokinetics of PHT in SF treated rats (4.5[plusmn]0.8 [micro]g/ml), PHT levels were significantly higher in MP rats pretreated with NIMO (Cmax: 6.8[plusmn]1.0 [micro]g/ml, p[lt]0.05 vs MP rats pretreated with SF) compared to MP animals with previous administration of SF., Thus, our results suggest that central pharmacokinetics of PHT was altered in epileptic rats by MP administration. The effect of NIMO on hipocampal concentrations of PHT suggested that P-gp is implicated in the reduced central bioavailability of PHT in MP epileptic rats., (Supported by University of Buenos Aires.)