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Study of gender-related pharmacokinetics of ezogabine in Egyptian volunteers by a validated LC-MS/MS bioanalytical method

Gender-based pharmacokinetics and/or pharmacodynamics differences can result in differences in treatment which can accordingly affect the drug safety and/or efficacy. A new validated bio-analytical LC-MS/MS method was developed for the estimation of ezogabine, a third-generation antiepileptic drug,...

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Detalles Bibliográficos
Autores principales: Elkady, Ehab F., Aboelwafa, Ahmed A., Fouad, Marwa A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961218/
https://www.ncbi.nlm.nih.gov/pubmed/31956446
http://dx.doi.org/10.1016/j.jare.2019.11.008
Descripción
Sumario:Gender-based pharmacokinetics and/or pharmacodynamics differences can result in differences in treatment which can accordingly affect the drug safety and/or efficacy. A new validated bio-analytical LC-MS/MS method was developed for the estimation of ezogabine, a third-generation antiepileptic drug, in human plasma using oxcarbazepine as an internal standard (IS) and to study the gender effect on the pharmacokinetic parameters in Egyptian human subjects. Liquid-liquid extraction of plasma samples was performed with diethyl ether: dichloromethane. The separation was accomplished in an isocratic mode with a mobile phase of a mixture of 5 mM ammonium acetate: methanol: acetonitrile pumped on a reversed phase C18 INERTSIL ODS-3 (5 µm, 150 × 4.6 mm). Multiple reaction monitoring was applied and operated by positive mode electrospray ionization. Male and female C(max) (p = 0.0308; CL = 95) and t(1/2) (p = 0.0301; CL = 95) were found to be significantly different using Mann-Whitney U test. These findings highlight the difference of ezogabine pharmacokinetics among populations. Further, gender-based ezogabine dose adjustment may be considered.