Pharmacogenetic markers of metabolic disorders in the treatment with valproic acid

Drokov, A. P.; Lipatova, L. V.; Shnayder, N. А.; Насырова, Р. Ф.

doi:10.17116/jnevro201811810282

Cited by 2 publications

(1 citation statement)

References 61 publications

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“…The administration of valproate to obese patients results in an increase in serum leptin levels compared to non-obese patients [ 91 ], but there is no answer yet as to which VPA metabolites induce this ADR. However, it is known that VPA and its active toxic metabolites can reduce the expression of the up-regulated gene 4/up-regulator of cell proliferation URG4/URGCP (URG4/URGCP) and CCND1 (Cyclin D1) genes and suppress the proliferation of neuroblastoma cells is a human-derived line cell used in scientific research SHY5Y [ 27 , 92 , 93 ].…”

Section: Pharmacometabolomics and Pharmacogenomics Of Valproic Acidmentioning

confidence: 99%

Therapeutic and Toxic Effects of Valproic Acid Metabolites

et al. 2023

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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).

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Section: Pharmacometabolomics and Pharmacogenomics Of Valproic Acidmentioning

confidence: 99%

Therapeutic and Toxic Effects of Valproic Acid Metabolites

et al. 2023

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Role of Pharmacogenetic Testing in the Risk and Safety Assessment of Valproates: The Ethnic Aspect (Review)

Shnayder,

Grechkina,

Arkhipov

et al. 2024

Bezopasnost' i risk farmakoterapii

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INTRODUCTION. Pharmacogenetic (PGx) testing plays a significant role in predicting the risk of adverse drug reactions (ADRs) associated with valproic acid (VPA) products, which are among the most prescribed medicinal products in neurology and psychiatry. However, the sensitivity and specificity of PGx screening panels may be insufficient as individual valproate metabolism varies across ethnically/racially diverse patient populations.AIM. The study aimed to identify implementation areas for a personalised approach to the development of PGx panels for assessing the safety and risk of valproate therapy in various ethnic and racial groups residing in the Russian Federation.DISCUSSION. The authors reviewed the results of population studies concerning the frequency of non-functional and low-function alleles of genes encoding isoenzymes that play key roles in VPA P-oxidation in the liver. This review focused on studies published in eLIBRARY.RU, PubMed, Scopus, and Google Scholar in 2012–2022. The inclusion criteria were full-text original articles, systematic reviews, meta-analyses, Cochrane reviews, and clinical cases in Russian or English. The analysis revealed that the need for personalised assessment of the risk and safety of VPA may depend on the frequency of risk alleles for slowing down VPA P-oxidation in the liver across racial and ethnic groups worldwide, and particularly in Russia. The authors identified new areas to implement the personalised approach to the development of PGx panels for assessing the safety and risk of valproate therapy with consideration of the rates of hepatic VPA P-oxidation in patients of different ethnic and racial backgrounds. However, the review of population-based associative genetic research from around the world demonstrated the current lack of clarity in the prospects of translating international findings directly into Russian clinical practice through the development of PGx panels due to Russia’s ethnic/racial diversity and vast territory.CONCLUSIONS. To increase the sensitivity and specificity of Russian PGx panels, bridging studies are required to extrapolate the associations established between the most common risk alleles and VPA P-oxidation disorders in other ethnic groups to a specific population of a specific Russian region.

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Pharmacogenetic markers of metabolic disorders in the treatment with valproic acid

Cited by 2 publications

References 61 publications

Therapeutic and Toxic Effects of Valproic Acid Metabolites

Therapeutic and Toxic Effects of Valproic Acid Metabolites

Role of Pharmacogenetic Testing in the Risk and Safety Assessment of Valproates: The Ethnic Aspect (Review)

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