Therapeutic and Toxic Effects of Valproic Acid Metabolites
Natalia A. Shnayder,
Violetta V. Grechkina,
Aiperi K. Khasanova,
Elena N. Bochanova,
Evgenia A. Dontceva,
Marina M. Petrova,
Azat R. Asadullin,
German A. Shipulin,
Kuanysh S. Altynbekov,
Mustafa Al-Zamil,
Regina F. Nasyrova
Affiliations
Natalia A. Shnayder
Institute of Personalized Psychiatry and Neurology, Shared Core Facilities, V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia
Violetta V. Grechkina
Institute of Personalized Psychiatry and Neurology, Shared Core Facilities, V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia
Aiperi K. Khasanova
Department of Psychiatry, Russian Medical Academy for Continual Professional Education, 125993 Moscow, Russia
Elena N. Bochanova
Shared Core Facilities “Molecular and Cell Technologies”, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia
Evgenia A. Dontceva
Shared Core Facilities “Molecular and Cell Technologies”, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia
Marina M. Petrova
Shared Core Facilities “Molecular and Cell Technologies”, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia
Azat R. Asadullin
Department of Psychiatry and Addiction, Bashkir State Medical University, 45000 Ufa, Russia
German A. Shipulin
Centre for Strategic Planning and Management of Biomedical Health Risks, 119121 Moscow, Russia
Kuanysh S. Altynbekov
Republican Scientific and Practical Center of Mental Health, Almaty 050022, Kazakhstan
Mustafa Al-Zamil
Department of Physiotherapy, Faculty of Continuing Medical Education, Peoples’ Friendship University of Russia, 11798 Moscow, Russia
Regina F. Nasyrova
Institute of Personalized Psychiatry and Neurology, Shared Core Facilities, V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia
Valproic acid (VPA) and its salts are psychotropic drugs that are widely used in neurological diseases (epilepsy, neuropathic pain, migraine, etc.) and psychiatric disorders (schizophrenia, bipolar affective disorder, addiction diseases, etc.). In addition, the indications for the appointment of valproate have been expanding in recent years in connection with the study of new mechanisms of action of therapeutic and toxic metabolites of VPA in the human body. Thus, VPA is considered a component of disease-modifying therapy for multiple tumors, neurodegenerative diseases (Huntington’s disease, Parkinson’s disease, Duchenne progressive dystrophy, etc.), and human immunodeficiency syndrome. The metabolism of VPA is complex and continues to be studied. Known pathways of VPA metabolism include: β-oxidation in the tricarboxylic acid cycle (acetylation); oxidation with the participation of cytochrome P-450 isoenzymes (P-oxidation); and glucuronidation. The complex metabolism of VPA explains the diversity of its active and inactive metabolites, which have therapeutic, neutral, or toxic effects. It is known that some active metabolites of VPA may have a stronger clinical effect than VPA itself. These reasons explain the relevance of this narrative review, which summarizes the results of studies of blood (serum, plasma) and urinary metabolites of VPA from the standpoint of the pharmacogenomics and pharmacometabolomics. In addition, a new personalized approach to assessing the cumulative risk of developing VPA-induced adverse reactions is presented and ways for their correction are proposed depending on the patient’s pharmacogenetic profile and the level of therapeutic and toxic VPA metabolites in the human body fluids (blood, urine).
