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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Jörn Lötsch - , Stanford University, Universitätsklinikum Frankfurt (Autor:in)
  • Birgit Kettenmann - , Friedrich-Alexander-Universität Erlangen-Nürnberg (Autor:in)
  • Bertold Renner - , Institut für Klinische Pharmakologie, Friedrich-Alexander-Universität Erlangen-Nürnberg (Autor:in)
  • David Drover - , Stanford University (Autor:in)
  • Kay Brune - , Friedrich-Alexander-Universität Erlangen-Nürnberg (Autor:in)
  • Gerd Geisslinger - , Universitätsklinikum Frankfurt (Autor:in)
  • Gerd Kobal - , Friedrich-Alexander-Universität Erlangen-Nürnberg (Autor:in)

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 (NON-MEM). 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 CQ2. 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.

Details

OriginalspracheEnglisch
Seiten (von - bis)77-84
Seitenumfang8
FachzeitschriftPharmaceutical Research
Jahrgang17
Ausgabenummer1
PublikationsstatusVeröffentlicht - 2000
Peer-Review-StatusJa

Externe IDs

PubMed 10714612
ORCID /0000-0003-0845-6793/work/139025181

Schlagworte

Schlagwörter

  • Diclofenac tablets, Diclofenac-Na effervescent, Double- blind four-way crossover study, Drug absorption, Pharmacodynamics, Population pharmacokinetics