Tag Archives: serum concentration

Valproic acid concentrations in people with epilepsy

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1117-1125, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1500_10.6.1117

Original Article

Serum concentrations of valproic acid in people with epilepsy: Clinical implication

[Concentraciones séricas de ácido valproico en personas con epilepsia: Implicación clínica]

Angel T. Alvarado1*, Juan Cotuá2, Maryori Delgado2, Alexis Morales3, Ana María Muñoz4, César Li Amenero5, María R. Bendezú6, Jorge A. García6, Doris Laos-Anchante6, Felipe Surco-Laos6, Berta Loja7, Mario Bolarte-Arteaga8, Mario Pineda-Pérez9

1International Research Network of Pharmacology and Precision Medicine (REDIFMEP), Human Medicine, San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

2Neurology and Neurosurgery of the Sabana Neurosabana, Sincelejo 700001, Colombia.

3Department of Toxicology and Pharmacology, Faculty of Pharmacy and Bioanalysis, Universidad Los Andes, 5101, Merida, Venezuela.

4Institute of Food Science and Nutrition, ICAN, San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

5Outpatient Clinic, Victor Larco Herrera Hospital, 15076, Lima, Peru.

6Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University of Ica, 11004, Ica, Peru.

7Environmental Engineering, Faculty of Engineering, San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

8Human Medicine, Continental University, Los Olivos 15304, Lima, Peru.

9Pharmacy and Biochemistry, Faculty of Health Sciences, Scientific University of the South, UCSUR, 15067, Lima, Peru.

*E-mail: angel.alvarado@usil.pe

Abstract

Context: Therapeutic drug monitoring (TDM) allows personalizing the dose of valproic acid in patients with epilepsy to optimize drug therapy, minimize adverse effects and detect interactions.

Aims: To determine valproic acid concentrations in serum samples from people with epilepsy and to analyze its clinical implications.

Methods: Cloned donor enzyme immunoassay; descriptive, cross-sectional, non-randomized, convenience recruitment study of 57 voluntary patients with epilepsy (n = 39 male, 68.42%; n = 18 female, 31.58%) aged between 19 and 62 years. After three months of treatment with valproic acid, a single blood sample was collected from each volunteer at a minimal concentration.

Results: Serum drug concentrations 51.30-100.10 mg/L (SD 5.94) and level/dose 2.17-5.31 (SD 1.14) were observed. Association was shown between the dose ratio/dose of valproic acid (R2 = 0.8693; p<0.05) and the Mann-Whitney U test (p<0.05). Valproic acid monotherapy and association with carbamazepine and phenytoin are not different between treatment groups (Mann-Whitney U test: p = 0.391 > α = 0.05).

Conclusions: Serum valproic acid concentrations are within the therapeutic range, and there is a significant inverse linear correlation between dose ratio/dose, which must be considered to personalize the dose and optimize the pharmacotherapeutic result.

Keywords: dose-dose relationship; epilepsy; serum concentration; therapeutic monitoring; valproic acid.

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Resumen

Contexto: La monitorización terapéutica del fármaco (TDM) permite personalizar la dosis de ácido valproico en pacientes con epilepsia, para optimizar la terapia farmacológica, minimizar los efectos adversos y detectar interacciones.

Objetivos: Determinar las concentraciones de ácido valproico en muestras de suero de personas con epilepsia, y analizar su implicancia clínica.

Métodos: Inmunoensayo de enzima donante clonada; estudio descriptivo, transversal, reclutamiento por conveniencia y no aleatorizado de 57 pacientes voluntarios con epilepsia (n = 39 masculinos, 68,42%; n =18 femenino, 31,58%) edad entre 19 y 62 años. Después de tres meses de tratamiento con ácido valproico, se colectó una sola muestra de sangre de cada voluntario a concentración mínima.

Resultados: Se observó concentraciones de fármaco en suero 51,30-100,10 mg/L (SD 5,94), nivel/dosis 2,17-5,31 (SD 1,14). Se mostró asociación entre relación dosis/dosis de ácido valproico (R2 = 0,8693; p<0,05), y Prueba U de Mann-Whitney (p<0,05). Monoterapia de ácido valproico y asociación con carbamazepina y fenitoína no son diferentes entre los grupos de tratamiento (Prueba U de Mann-Whitney: p = 0,391 > α = 0,05).

Conclusiones: Las concentraciones de ácido valproico en suero se encuentra dentro del intervalo terapéutico y existe una correlación lineal inversa significativa entre relación dosis/dosis, que se deben considerar para personalizar la dosis, y optimizar el resultado farmacoterapéutico.

Palabras Clave: ácido valproico; concentración sérica; relación dosis-dosis; epilepsia; seguimiento terapéutico.

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Citation Format: Alvarado AT, Cotuá J, Delgado M, Morales A, Muñoz AM, Li C, Bendezú MR, García JA, Laos-Anchante D, Surco-Laos F, Loja B, Bolarte-Arteaga M, Pineda-Pérez M (2022) Serum concentrations of valproic acid in people with epilepsy: Clinical implication. J Pharm Pharmacogn Res 10(6): 1117–1125. https://doi.org/10.56499/jppres22.1500_10.6.1117
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