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

Published online by Cambridge University Press:  26 August 2025

E. I. Mochalova ,
T. V. Shushpanova ,
E. V. Gutkevich ,
T. P. Novozheeva ,
O. V. Shushpanova ,
I. N. Smirnova  and
N. E. Kolomiets
E. I. Mochalova*
Affiliation:
National Research Tomsk State University, Tomsk
T. V. Shushpanova
Affiliation:
Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
E. V. Gutkevich
Affiliation:
Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences National Research Tomsk State University, Tomsk
T. P. Novozheeva
Affiliation:
Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
O. V. Shushpanova
Affiliation:
Mental Health Research Center, Moscow
I. N. Smirnova
Affiliation:
Tomsk Research Institute of Balneology and Physiotherapy, branch of the Federal Scientific and Clinical Center for Medical Rehabilitation and Balneology of the Federal Medical and Biological Agency
N. E. Kolomiets
Affiliation:
Siberian State Medical University of the Ministry of Health of the Russia, Tomsk Kemerovo State Medical University of the Ministry of Health of the Russia, Kemerovo, Russian Federation
*
*Corresponding author.

Abstract

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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

Information

Type
Abstract
Information
European Psychiatry , Volume 68 , Special Issue S1: Abstracts of the 33rd European Congress of Psychiatry , April 2025 , pp. S1034
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of European Psychiatric Association
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