Kinetics and Dynamics of Lamotrigine in 3-Mercaptopropionic Acid induced-seizures

HÖCHT C, LAZAROWSKI A, OPEZZO JA, TAIRA C, GIRARDI E.

Rosario-Santa Fe

Congreso; XLI Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2009

SAFE

We studied pharmacokinetics and pharmacodynamics of lamotrigine (LTG) in an experimental model of epilepsy, induced by repetitive 3-mercaptopropionic acid (MP) administration. Wistar rats were divided in 4 groups: Groups A received a single dose i.p. of MP (40-45mg/kg) daily injected during 10 days. During the same period, group B, was daily treated with LTG (20mg/kg), previous to MP administration, group C received nimodipine (2mg/kg) 1 hour previous to MP and as control (groupD) rats were injected with saline solution (V). Hippocampal and plasma pharmacokinetics of LTG were evaluated in the different groups after single iv administration of 10 mg/kg by using central microdialysis and traditional blood sampling. Pharmacodynamics studies showed that LTG and Nimo did not protect from MP induces seizures. In rats pretreated with V, hippocampal LTG levels were similar in MP rats (maximal concentration (Cmax):1.36±0.42 µg/ml) compared to C animals (Cmax: 1.80±0.19 µg/ml µg/ml). NIMO pretreatment did not modify central kinetics of LTG in C and MP animals (C rats: Cmax: 1.68±0.50 µg/ml; MP rats: Cmax: 1.58±0.41 µg/ml). Our results indicate that LTG does not protect from MP seizures. Hippocampal LTG levels were similar in MP rats than in controls and in the presence of the Pgp inhibitor NIMO, suggesting that LTG is not a good substrate of P-gp.