Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma

Malygin, A.S.; Popov, N.S.; Демидова, М. А.; Kudrayshova, M. N.

doi:10.17749/2077-8333.2018.10.2.035-042

Cited by 3 publications

(1 citation statement)

References 6 publications

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“…Furthermore, most VPA is bound to protein in the blood. However, it is the unbound portion of the drug that is the active component [10]. Therefore, a patient with a condition resulting in lower-than-normal amounts of protein in their blood may be at increased risk of having a supratherapeutic or excess amount of circulating VPA and, therefore, require TDM of both total and free VPA levels [11].…”

Section: Effect Of Variable Alleles Of Genes Encoding Cytochrome P450...mentioning

confidence: 99%

Ethnic Aspects of Valproic Acid P-Oxidation

Shnayder,

Grechkina,

Trefilova

et al. 2024

Biomedicines

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The safety of the use of psychotropic drugs, widely used in neurological and psychiatric practice, is an urgent problem in personalized medicine. This narrative review demonstrated the variability in allelic frequencies of low-functioning and non-functional single nucleotide variants in genes encoding key isoenzymes of valproic acid β-oxidation in the liver across different ethnic/racial groups. The sensitivity and specificity of pharmacogenetic testing panels for predicting the rate of metabolism of valproic acid by P-oxidation can be increased by prioritizing the inclusion of the most common risk allele characteristic of a particular population (country).

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Section: Effect Of Variable Alleles Of Genes Encoding Cytochrome P450...mentioning

confidence: 99%

Ethnic Aspects of Valproic Acid P-Oxidation

Shnayder,

Grechkina,

Trefilova

et al. 2024

Biomedicines

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Pharmacokinetic Interactions of Phenosanic Acid with Valproic Acid and Carbamazepine in Dogs

Karlina¹,

Косман²,

Makarov³

et al. 2022

Bezopasnost' i risk farmakoterapii

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Phenosanic acid prevents convulsions, reduces the frequency of epileptic seizures, and improves cognitive, intellectual and mnestic functions in patients with epilepsy. Therefore, phenosanic acid-based medicinal products are promising candidates for inclusion in combination antiepileptic therapy. In order to combine medicinal products rationally and ensure that the therapy is safe, it is useful to study the pharmacokinetic interaction of medicinal products planned for clinical co-administration.The aim of the study was to examine single-dose pharmacokinetic interactions between Dibufelon® 200 mg capsules (PIQ-PHARMA LLC, Russia) and two medicinal products planned for clinical co-application with it, namely, valproic acid and carbamazepine, in sexually mature dogs.Materials and methods: the study included medicinal products of phenosanic acid (Dibufelon® 200 mg capsules by PIQ-PHARMA LLC, Russia), valproic acid (300 mg prolonged-release film-coated tablets), and carbamazepine (200 mg tablets). The medicinal products were administered to beagle dogs (2 groups of 9 males each) as a single oral dose separately and in the following combinations: phenosanic acid with valproic acid and phenosanic acid with carbamazepine. Dose selection involved adjusting maximum human therapeutic doses using interspecies conversion factors. Phenosanic acid was administered at a dose of 24 mg/kg; valproic acid and carbamazepine were administered at a dose of 60 mg/kg. Blood sampling took place at baseline and in 0.5, 0.75, 1, 2, 4, 6, 8, 10, and 24 h after dosing. Plasma concentrations of active substances were determined by HPLC-UV. Pharmacokinetic interactions were evaluated by changes in the main pharmacokinetic parameters (Сmax, Тmax, AUC0-24, MRT, Т1/2).Results: the study demonstrated rapid gastrointestinal absorption and prolonged systemic circulation of phenosanic acid administered separately (Tmax 2–4 h, T1/2 13–28 h) and combined with valproic acid (Tmax 2 h, T1/2 22 h). When administered with carbamazepine, phenosanic acid was eliminated from the systemic blood flow faster (T1/2 7.4 h).Conclusions: co-administration of phenosanic acid and valproic acid medicinal products had no significant effect on their respective pharmacokinetics. Whereas, the combination of phenosanic acid and carbamazepine demonstrated a significant decrease in the Tmax values of phenosanic acid and the MRT values of carbamazepine. The pharmacokinetic changes suggestive of a possible interaction between phenosanic acid and carbamazepine need further clinical investigation.

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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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Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma

Cited by 3 publications

References 6 publications

Ethnic Aspects of Valproic Acid P-Oxidation

Ethnic Aspects of Valproic Acid P-Oxidation

Pharmacokinetic Interactions of Phenosanic Acid with Valproic Acid and Carbamazepine in Dogs

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

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