Stereoselective Pharmacokinetics of Ketoprofen After Oral Administration of Modified-Release Formulations in Caucasian Healthy Subjects

Dublin Core

Título

Stereoselective Pharmacokinetics of Ketoprofen After Oral Administration of Modified-Release Formulations in Caucasian Healthy Subjects

Tema

ANTIINFLAMATORIOS
FARMACOCINETICA
FORMULACION
BIBLIOGRAFIA NACIONAL QUIMICA
2015
KETOPROFENO

Abstract

Background and Objectives Ketoprofen, a potent nonsteroidal anti-inflammatory drug, is clinically administered as a racemic mixture. One of the possible metabolism routes of ketoprofen is the inversion of the R- to S-enantiomer in the gastrointestinal tract. Ketoprofen, as a weak acid drug, might undergo recirculation through pancreatic/intestinal juices. The aim of the work was to investigate if a plasma-gastrointestinal tract recirculation of ketoprofen could explain its R-to-S chiral inversion after the oral administration of two modified-release formulations: a gastro-resistant delayed-release tablet (Reference) and an extended-release-plus-immediate-release bilayer tablet (Test). Methods Sixteen healthy Caucasian volunteers (eight women and eight men) participated in a ketoprofen bioequivalence study. Both formulations were administered with and without food. In both cases, standard meals were given throughout the experiment. R- and S-enantiomers were measured separately using a validated HPLC–UV chiral method. Mean concentration–time profiles of ketoprofen enantiomers in plasma were obtained for men and women. Area under the plasma concentration–time curve, maximum ketoprofen plasma concentration, and time-to-peak were also computed for both isomers, both modes of administration, and both sexes. S/R concentration ratio was assessed as an indicator of enantiomer chiral inversion rate. Results Differences in the pharmacokinetics of S- and R-ketoprofen enantiomers were found after the Test administration. S-Ketoprofen presented a lower plasma exposure compared to R-enantiomer. However, the S/R concentration ratio increased 1 h (in men) and 2 h (in women) after meal intakes. This was related to pancreatic and/or intestinal and/or biliary secretions of the drug, followed by reabsorption and conversion of the R- to the S-isomer. The lower intestinal pH reported for men would lead to a higher oral bioavailability of the Test formulation and a higher reabsorption of both ketoprofen isomers in this sex. Hence, a higher rise of the S/R concentration ratio could be observed in men. No significant differences between isomers exposure were detected in both sexes after the Reference administration. Different lag times were observed after fed and fasting administration of this formulation; however, drug absorption coincided with food ingestion. Then, drug recirculation affected the S/R ratio from the beginning of drug exposure, minimizing the difference between isomers disposition. Conclusions R-to-S conversion rate could be mainly associated with several passages of the drug through the intestinal mucosa. The concentration–time profiles of ketoprofen in plasma after the administration of both formulations evidenced R-to-S conversion of recirculating drug following meal intakes.

Autor

Lorier, Marianela
Magallanes, Laura
Ibarra, Manuel
Guevara, Natalia
Vázquez, Marta

Fuente

European Journal of Drug Metabolism and Pharmacokinetics 2015. -- 7 p.

Editor

Springer

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

DOI: 10.1007/s13318-015-0313-2
Fecha de agregación
March 16, 2016
Colección
Bibliografía Nacional Química
Tipo de Elemento
Document
Etiquetas
, ,
Citación
Lorier, Marianela, “Stereoselective Pharmacokinetics of Ketoprofen After Oral Administration of Modified-Release Formulations in Caucasian Healthy Subjects,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed September 29, 2020, http://riquim.fq.edu.uy/items/show/3778.
Archivos