Enzyme-inducing effect of the original anticonvulsant on the liver monooxygenase system – prospects for clinical use in the treatment of paroxysmal disorders

Introduction It is necessary to know how the pharmacokinetics of psychotropic drugs changes in the body of patients during their long-term use. Objectives To study the pharmacokinetic parameters of the anticonvulsant galodif in experimental rats at different times of drug administration. Methods Galodif (meta-chlorobenzhydryl urea, 100 mg/kg) was administered in rats (in suspension, intragastrically) for: 1, 5 and 15 days. Galodif was determined in the microsomal fraction of rat liver. Pharmacokinetic parameters were calculated by a model-independent method of statistical moments. The statistical significance of differences was assessed using the Kolmogorov-Smirnov λ-test at p<0.05. Results A single administration of galodif to rats is accompanied by a slowdown in its elimination from the body: the values of T1/2 (18.82±6.25h), MRT (22.41±7.07h), MET (10.64±2.84h), AUC (15.01±4.86 mcg/ml) increase, indicating the retention of galodif in the body tissues. A 5-fold administration of galodif stimulates the elimination of the drug: T1/2 (2.22±0.52*h), AUC (3.68±0.79*mcg/ml), MRT (2.95±0.73*h), MET (3.00±0.65*h) decrease. The pharmacokinetic parameters of the drug indicate a pronounced tissue availability of galodif molecules. With a 15-fold administration of galodif, the elimination of the drug from the body slows down somewhat, remaining accelerated relative to a single administration: T1/2 (10.79±2.90*h), MRT (3.97±1.03*h), MET (12.05±4.10*h), AUC (19.28±7.13*mcg/ml). The revealed changes in kinetic parameters during long-term administration of galodif to rats stimulate the elimination of the drug by inducing the microsomal liver oxidative system. Conclusions The choice of a drug that combines anticonvulsant and detoxifying properties is of great importance in long-term therapy of paroxysmal disorders, epilepsy and alcoholism. Disclosure of Interest None Declared