Different oral phenytoin administration regimens could modify its chronic exposure and its saliva/plasma concentration ratio

Dublin Core

Título

Different oral phenytoin administration regimens could modify its chronic exposure and its saliva/plasma concentration ratio

Tema

ANTIEPILEPTICOS
FENITOINA
BIBLIOGRAFIA NACIONAL QUIMICA
2014

Abstract

The aim of the present study was to compare plasma and saliva pharmacokinetic data obtained in healthy subjects after two different phenytoin administration regimens, having the same administration rate but different dosing interval, in order to investigate if efflux transporter induction at the blood brain barrier could be minimized, and hence a new approach for avoiding refractory epilepsy might be proposed. Six from twelve volunteers, to whom 600 mg every 72 h or 100 mg every 12 h of phenytoin were administered during 10 days, completed a two-way, two-period crossover study. Two fractions of stimulated saliva were collected simultaneously with plasma samples throughout a scheduled 24-hour period on day 10, and during the subsequent 4-day washout period.

Average plasma (P) concentrations of both the parent drug (p<0.01) and the main metabolite (p-hydroxyphenylphenytoin, p<0.05) showed higher values when 600 mg each 72 h were given. Also, the saliva first-fraction (S1) average concentration was higher (p<0.05) after 600 mg every 72 h. Conversely, S1/P average concentration ratio was higher (p<0.01) after 100 mg every 12 h. Half-lives, metabolic ratios, saliva second-fraction (S2) average concentrations, and S1/S2 ratios of average levels were not significantly different between treatments.

Results reveal that, even though the input rate was kept constant, higher doses given at long dosing intervals displayed higher systemic exposures and lower saliva/plasma exposure ratio than lower doses given at short intervals . Our hypothesis, supported by studies carried out with rats and theoretical approaches, is that efflux transporter overexpression at hepatocytes and at salivary cells would be induced by the higher local phenytoin exposures provoked by 600 mg every 72 h and by the persistent systemic exposures provoked by 100 mg every 12 h, respectively. The maintenance of systemic phenytoin concentration would be foreseen as one of the causes leading to antiepileptic treatment refractoriness, since a higher brain-to-plasma transportation of drug could be induced.

Maybe once-daily dosing of phenytoin would be preferable to twice or three times a day administration regimens. Despite the fact that avoiding peak-trough oscillation was always the aim of pharmacotherapy, it might be more appropriate for patients under phenytoin treatments to increase both dose and dosing interval in order not to contribute to the installation of pharmacoresistance.

Autor

Alvariza, Silvana
Ibarra, Manuel
Vázquez, Marta

Fuente

Journal of Medical and Pharmaceutical Innovation v. 1, no. 6S, 2014.-- p. 35-43

Editor

HE BAI (Kelvin)

Fecha

2014

Derechos

Información sobre Derechos de Autor

(Por favor lea este aviso antes de abrir los documentos u objetos)

La legislación uruguaya protege el derecho de autor sobre toda creación literaria, científica o artística, tanto en lo que tiene que ver con sus derechos morales, como en lo referente a los derechos patrimoniales con sujeción a lo establecido por el derecho común y las siguientes leyes

(LEY 9.739 DE 17 DE DICIEMBRE DE 1937 SOBRE PROPIEDAD LITERARIA Y ARTISTICA CON LAS MODIFICACIONES INTRODUCIDAS POR LA LEY DE DERECHO DE AUTOR Y DERECHOS CONEXOS No. 17.616 DE 10 DE ENERO DE 2003, LEY 17.805 DE 26 DE AGOSTO DE 2004, LEY 18.046 DE 24 DE OCTUBRE DE 2006 LEY 18.046 DE 24 DE OCTUBRE DE 2006)

ADVERTENCIA - La consulta de este documento queda condicionada a la aceptación de las siguientes condiciones de uso: Este documento es únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con fines de lucro. Esta reserva de derechos afecta tanto los datos del documento como a sus contenidos. En la utilización o cita de partes debe indicarse el nombre de la persona autora.

Formato

PDF

Idioma

Inglés

Tipo

Artículo

Identificador

ISSN: 2347 - 8136

Document Item Type Metadata

Original Format

PDF
Fecha de agregación
November 16, 2017
Colección
Bibliografía Nacional Química
Tipo de Elemento
Document
Etiquetas
,
Citación
Alvariza, Silvana, “Different oral phenytoin administration regimens could modify its chronic exposure and its saliva/plasma concentration ratio,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed December 6, 2021, http://riquim.fq.edu.uy/items/show/4764.
Archivos