Valérie Cosson, Pharm D(1), Pr Jean-Michel Scherrmann(2), ElianeFuseau,PhD(1)
(1) Clinical Pharmacokinetics Department, Glaxo Research and Development Limited, Greenford, UK; (2) Faculté de Pharmacie, Université René Descartes - Paris V, France
Sumatriptan is a highly potent, selective 5-HT1 agonist and is effective in the acute treatment of migraine and cluster headache.
The bioavailability of oral Sumatriptan in healthy subjects is low, 14%, mainly due to first pass metabolism. Sumatriptan is rapidly absorbed and often displays multiple peaks and a prolonged absorption. The elimination half-life after oral doses is about to 2 hours. The apparent volume of distribution is 170 l, and plasma clearance 70 l/h. The inter-subject variability in absorption and disposition is large (CV= 60%).
In order to better estimate the disposition parameters, we modelled the absorption, in a retrospective analysis of a large database of drug development studies, after intravenous and/or oral Sumatriptan .
Simple simulations provided the kinetic model:
- absorption: first order input with a lag-time and a zero order input with another lag-time
- disposition : bi-exponential
NONMEM was used to fit individual subject data, and the PK parameters were compared to those from deconvolution analysis. The model was then applied to the larger database, including patients with sparse concentration time points. A small number of demographic covariates was also included.
Reference: PAGE 3 (1994) Abstr 857 [www.page-meeting.org/?abstract=857]
Poster: poster