Abstract
Genetically epilepsy-prone (GEP) rats, in comparison with the normal Sprague-Dawley animals, demonstrated an enhanced susceptibility to seizures induced by the administration of aminophylline. It was considered that this phenomenon may be due to a difference in the kinetic profile of theophylline between the two strains. To explore this possibility, both GEP and normal rats were intraperitoneally dosed with aminophylline (556 μmol kg−1). Venous blood samples were drawn at different time points after the injection, and the serum levels of theophylline were measured. Theophylline half-life appeared significantly longer in the GEP than in the normal rats. The GEP rats also showed a reduced total serum theophylline clearance and an enhanced volume of distribution in comparison with the normal rats. In addition, we found larger concentrations of theophylline in the serum of GEP than in the serum of normal rats 15, 240 and 480 min after the injection of aminophylline. We conclude that the enhanced susceptibility to seizure induced by aminophylline observed in the GEP rats is, at least in part, related to altered pharmacokinetics of the compound in this strain.
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