Titre du document / Document title

Population pharmacokinetics of fast release oral diclofenac in healthy volunteers: Relation to pharmacodynamics in an experimental pain model

Auteur(s) / Author(s)

LÖTSCH J. ⁽¹⁾ ; KETTENMANN B. ⁽²⁾ ; RENNER B. ⁽²⁾ ; DROVER D. ⁽¹⁾ ; BRUNE K. ⁽²⁾ ; GEISSLINGER G. ⁽³⁾ ; KOBAL G. ⁽²⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Stanford University School of Medicine, Department of Anesthesia, 300 Pasteur Drive, Stanford, California 94305-5640, ETATS-UNIS
⁽²⁾ Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Fahrstr. 17, 91054 Erlangen, ALLEMAGNE
⁽³⁾ Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität, Theodor Stern Kai 7, 60590 Frankfurt am Main, ALLEMAGNE

Résumé / Abstract

Purpose. Population pharmacokinetics of a fast release diclofenac were assessed with special focus on pharmacodynamic implications. Methods. In a double blind four-way crossover study, 20 healthy volunteers received orally 50 and 100 mg diclofenac-Na effervescent (fast-release NSAID), 50 mg diclofenac tablets (control), or placebo. Population pharmacokinetics of the fast release diclofenac were assessed using a nonlinear mixed effects modeling approach (NONMEM). Analgesic effects were investigated by means of an experimental pain model based on both pain-ratings and cortical evoked potentials after specific stimulation of nasal nociceptors with short pulses of gaseous CO₂. Results. Pharmacokinetics of fast release diclofenac were best described by a two-compartment population model, with an estimated terminal half-life of 1.2 hours. Pharmacokinetics of diclofenac tablets were highly variable and a population pharmacokinetic model could not be obtained. As an indication of an early onset of analgesic effects, 100 mg fast release diclofenac but not the tablets significantly reduced the amplitudes of pain-related evoked potentials at 30 min after administration. Conclusions. Earlier drug absorption and lower pharmacokinetic variability of the fast-release formulation are likely to be preserved in a population.

Revue / Journal Title

Pharmaceutical research   ISSN 0724-8741   CODEN PHREEB 

Source / Source

2000, vol. 17, n^o1, pp. 77-84 (28 ref.)

Langue / Language

Anglais

Editeur / Publisher

Springer, New York, NY, ETATS-UNIS  (1984) (Revue)

Mots-clés anglais / English Keywords

Diclofenac ; Non steroidal antiinflammatory agent ; Pharmacokinetics ; Human ; Normal ; Oral administration ; Tablet ; Dosage form ; Immediate release form ; Release ; Active ingredient ; Absorption ; Modeling ; Pharmacokinetic pharmacodynamic relationship ; Blood plasma ; Arylacetic acid derivatives ;

Mots-clés français / French Keywords

Diclofénac ; Antiinflammatoire non stéroïde ; Pharmacocinétique ; Homme ; Normal ; Voie orale ; Comprimé ; Forme pharmaceutique ; Forme libération immédiate ; Libération ; Principe actif ; Absorption ; Modélisation ; Relation pharmacocinétique pharmacodynamie ; Plasma sanguin ; Arylacétique acide dérivé ;

Mots-clés espagnols / Spanish Keywords

Diclofenaco ; Antiinflamatorio no esteroide ; Farmacocinética ; Hombre ; Normal ; Vía oral ; Tableta ; Forma farmacéutica ; Forma liberación inmediata ; Liberación ; Principio activo ; Absorción ; Modelización ; Relación farmacocinética farmacodinamia ; Plasma sanguíneo ; Arilacético ácido derivado ;

Localisation / Location

INIST-CNRS, Cote INIST : 20257, 35400009125866.0120