onr:"swepub:oai:DiVA.org:uu-91078"
Search: onr:"swepub:oai:DiVA.org:uu-91078" > A turnover model of...
- 1 of 1
- Previous record
- Next record
- To hitlist
- Äbelö, AngelaUppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi (author)
A turnover model of irreversible inhibition of gastric acid secretion by omeprazole in the dog
- Article/chapterEnglish2000
Publisher, publication year, extent ...
- 2000
- printrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:uu-91078
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-91078URI
Supplementary language notes
- Language:English
- Summary in:English
Part of subdatabase
- SwePubSwePub
Classification
Notes
- A turnover model for irreversible inhibition of gastric acid secretion by omeprazole in gastric fistula dogs was developed using data from studies with both short- and long-term measurement periods. In the short-term experiments, after stimulation of acid secretion with histamine, the dogs were infused i.v. with omeprazole and acid secretion was measured for 5 h. Dose and infusion times were varied to produce different concentration-time profiles and schedule dependence in the inhibitory effect of omeprazole was observed. In the long-term experiments, dogs were given single intraduodenal doses, which inhibited the acid secretion for several days. Combining the short-term and long-term data allowed the observation of a biphasic recovery of acid secretion that was described by the turnover model. Second order association rate constants (k(ome)) for the covalent binding of omeprazole to H(+),K(+)-ATPase were estimated to 11 and 3.0 l/micromol/h for the i.v. and intraduodenal experiments, respectively. The apparent turnover rate constant of the enzyme (k(out)) was 0.013 h(-1) and the corresponding half-life of inhibition of acid secretory capacity was 54 h. The potency, calculated as k(out) over k(ome), was 4.3 and 1.2 nM for the intraduodenal and i.v. doses, respectively. Allometric scaling of the model resulted in trustworthy predictions for observations previously done in humans. The model predicted a good correlation between maximal inhibitory effect and exposure (area under the plasma concentration curve). The time dependence in this relation was also predicted by the model.
Added entries (persons, corporate bodies, meetings, titles ...)
- Eriksson, Ulf G (author)
- Karlsson, Mats O.Uppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi,Farmakometri(Swepub:uu)matskarl (author)
- Larsson, Håkan (author)
- Gabrielsson, Johan (author)
- Uppsala universitetAvdelningen för farmakokinetik och läkemedelsterapi (creator_code:org_t)
Related titles
- In:Journal of Pharmacology and Experimental Therapeutics295:2, s. 662-6690022-35651521-0103
Internet link
Find in a library
- Journal of Pharmacology and Experimental Therapeutics (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Äbelö, Angela
- Eriksson, Ulf G
- Karlsson, Mats O ...
- Larsson, Håkan
- Gabrielsson, Joh ...
- Articles in the publication
- Journal of Pharm ...
- By the university
- Uppsala University
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
