Therapeutic and Toxic Effects of Valproic Acid Metabolites.
acetylation
adverse drug reaction
blood metabolite
glucuronidation
oxidation
personalized approach
pharmacogenomics
pharmacometabolomics
risk factor
urinal metabolite
valproic acid
Journal
Metabolites
ISSN: 2218-1989
Titre abrégé: Metabolites
Pays: Switzerland
ID NLM: 101578790
Informations de publication
Date de publication:
16 Jan 2023
16 Jan 2023
Historique:
received:
26
12
2022
revised:
11
01
2023
accepted:
12
01
2023
entrez:
21
1
2023
pubmed:
22
1
2023
medline:
22
1
2023
Statut:
epublish
Résumé
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).
Identifiants
pubmed: 36677060
pii: metabo13010134
doi: 10.3390/metabo13010134
pmc: PMC9862929
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
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