Biological Markers of the Antiepileptic Drugs Efficacy and Safety: Pharmacogenetics and Pharmacokinetics

Насырова, Р. Ф.; Sivakova, N. A.; Lipatova, L. V.; Ivashchenko, Dmitriy V.; Sosina, K. A.; Drokov, A. P.; Shnayder, N. А.

doi:10.20333/2500136-2017-1-17-25

Cited by 12 publications

(6 citation statements)

References 9 publications

(13 reference statements)

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“…JME is a widespread form of GGE, which includes myoclonic seizures, sometimes other seizure types (generalized tonic-clonic seizures, absences), onset in adolescence, and typical EEG changes as generalized spike and polyspike waves 4-6 Hz discharges with a normal background EEG [16,17]. The age of onset of JME covers a wide range from 8 to 36 years of age, with a peak onset from 12 to 18 years of age [4,5,18].…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic characteristics of juvenile myoclonic epilepsy

Шилкина

Zobova

Domoratskaya

et al. 2021

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Juvenile myoclonic epilepsy (JME) is reported as a clinically and genetically heterogeneous disease with a high risk of inheritance. The aim of the study was to establish phenotype features and genetic risk factors for juvenile myoclonic epilepsy to advance existing approaches of prevention, treatment, and observation of patients with JME. Methods: anamnestic; clinical; neurophysiological (EEG); neuroradiological (MRI), neuropsychological; laboratory (DNA-diagnostics). JME starts with absences more frequently in females as compared to males (32.0% vs. 15.4%), and with GTCS and myoclonic in males as compared to females (46.2% and 36.5% vs. 36.0% and 31.2%, respectively). The 1st phenotype of JME was more frequently encountered in male individuals in comparison with female ones (55.8% vs. 34.7%), and the 2nd phenotype was more frequently encountered in female individuals in comparison with male ones (16.9% vs. 5.8%). Homozygous carriage of the T allele of the GJD2 gene (rs3743123) was associated with the development of JME in the study population, OR = 2.66 (95% CI 1.24 to 5.74). 41.5% of patients with JME have a slow metabolizer pharmacogenetic status, which is a risk factor for pseudo-pharmacoresistance and the development of adverse drug reactions.

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Section: Discussionmentioning

confidence: 99%

Clinical and genetic characteristics of juvenile myoclonic epilepsy

Шилкина

Zobova

Domoratskaya

et al. 2021

jour

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“…Numerous studies have shown that human cytochrome P450 (CYP) isoenzymes play a crucial role in VPA metabolism [ 62 , 63 ]. A key CYP-mediated branch of the VPA pathway produces the metabolites 4-hydroxy(OH)-VPA and 5-OH-VPA via hepatic cytochrome P450 isoenzymes CYP2C9, CYP2B6, and CYP2A6.…”

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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“…ìàêîëîãèè [2][3][4]. Îöåíêó ýôôåêòèâíîñòè íîâûõ ÏÝÏ íà ñòàäèè äîêëèíè÷åñêèõ èññëåäîâàíèé êëàññè÷åñêè îñóùåñòâëÿþò íà aeèâîòíûõ ìîäåëÿõ ýïèëåïñèè è ñïðîâîöèðîâàííûõ ðàçëè÷íûìè ìåòîäàìè ñóäîðîaeíûõ ïðèïàäêîâ.…”

Section: __________________________unclassified

“…Îöåíêó ýôôåêòèâíîñòè íîâûõ ÏÝÏ íà ñòàäèè äîêëèíè÷åñêèõ èññëåäîâàíèé êëàññè÷åñêè îñóùåñòâëÿþò íà aeèâîòíûõ ìîäåëÿõ ýïèëåïñèè è ñïðîâîöèðîâàííûõ ðàçëè÷íûìè ìåòîäàìè ñóäîðîaeíûõ ïðèïàäêîâ. Ñ ýòîé öåëüþ èñïîëüçóþòñÿ ðàçëè÷íûå ìåòîäèêè: ìåõàíè÷åñêèå (òðàâìàòèçàöèÿ ñòðóêòóð öåíòðàëüíîé íåðâíîé ñèñòåìû, áîëåâîå âîçäåéñòâèå); ôèçè÷åñêèå (çâóêîâûå è ñâåòîâûå ðàçäðàaeåíèÿ, ãèïåðòåðìèÿ, âîçäåéñòâèå ýëåêòðè÷åñòâîì); àïïëèêàöèè ìåòàëëîâ (íàíåñåíèå íà ïîâåðõíîñòü êîðû ãîëîâíîãî èëè èíòðàöåðåáðàëüíîå ââåäåíèå ñîåäèíåíèé ìåòàëëîâ: ãèäðîêñèäà àëþìèíèÿ, ñóëüôàòà öèíêà, õëîðèäà êîáàëüòà); õèìè÷åñêèå ìåòîäû; à òàêaeå ãåíåòè÷åñêèå ìîäåëè ýïèëåïñèè [4,5].…”

Section: __________________________unclassified

Modeling of chronic epilepsy in animals through chemical methods

et al. 2020

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According to the World Health Organization, the prevalence of epilepsy in the world is high, at about 0.5–1% of the world’s population. In 20–40% of cases, according to various sources, it is not possible with standard treatment methods to achieve control over attacks, which significantly impairs the patient’s quality of life, increases economic costs, and poses a difficult task for the doctor to select the optimal treatment to reduce the frequency of attacks. This explains the urgency of creating new and modifying classical antiepileptic drugs (AEDs), as well as finding optimal and safe ways of administering and delivering the drugs. To study the mechanisms of AEDs’ effect on various pathways of epileptogenesis, simulation of convulsive seizures and chronic epilepsy in animals is used; for this purpose, mechanical, physical, chemical, and genetic models of epilepsy are used. The present review discusses chemical models of chronic epilepsy, which are most often used in experimental neuroscience today. It also describes the characteristics, advantages and disadvantages of each of them, the specificity of the study where they can be used and the assessment scales for epileptic seizures in animals.

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Biological Markers of the Antiepileptic Drugs Efficacy and Safety: Pharmacogenetics and Pharmacokinetics

Cited by 12 publications

References 9 publications

Clinical and genetic characteristics of juvenile myoclonic epilepsy

Clinical and genetic characteristics of juvenile myoclonic epilepsy

Therapeutic and Toxic Effects of Valproic Acid Metabolites

Modeling of chronic epilepsy in animals through chemical methods

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