Sökning: onr:"swepub:oai:DiVA.org:uu-91079" >
Pharmacodynamic mod...
Pharmacodynamic modelling of reversible gastric acid pump inhibition in dog and man
-
- Äbelö, Angela (författare)
- Uppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi
-
Gabrielsson, Johan (författare)
-
Holstein, Björn (författare)
-
visa fler...
-
Eriksson, Ulf G (författare)
-
Holmberg, Johan (författare)
-
- Karlsson, Mats O. (författare)
- Uppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi,Farmakometri
-
visa färre...
-
(creator_code:org_t)
- 2001
- 2001
- Engelska.
-
Ingår i: European Journal of Pharmaceutical Sciences. - 0928-0987 .- 1879-0720. ; 14:4, s. 339-346
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- H 335/25, a 4-amino quinoline, belongs to a new class of reversible gastric acid pump inhibitors. A potential advantage of such drugs over the irreversible proton pump inhibitors (PPIs) is better control over the effect-time profile. Dose escalation studies were performed to characterize the effect on acid secretion in dogs (n=24) and healthy male subjects (n=12). The effect-time profile was delayed compared to the concentration-time profile. A model-based approach, using non-linear mixed effects modelling, was applied to quantify and elucidate the mechanism for the delayed effect. Three different models were investigated: (1) a slow equilibration preceding the formation of drug-enzyme complex, modelled by an effect-compartment, (2) a slow equilibration between free drug, free enzyme and drug-enzyme complex, described by a kinetic binding model, and (3) a delay between enzyme inhibition and the measured response, described by an indirect response model. Model 2 was shown to be superior to models 1 and 3, for both dog and human data. The dissociation rate constant, k(off), was estimated to be 0.85 and 0.88 h and the calculated equilibration constant, K(d), was 160 and 250 nM in dog and man, respectively. Simulations of the predicted time-course of the effect beyond the 4-5-h observation period was similar for the three models.
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas