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A semi-mechanistic ...
A semi-mechanistic model for characterization of regional absorption properties and prospective prediction of plasma concentrations following administration of new modified release formulations
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- Bergstrand, Martin, 1977- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometrics Research Group
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Söderlind, Erik (författare)
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Eriksson, Ulf G (författare)
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Weitschies, Werner (författare)
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- Karlsson, Mats O (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometrics Research Group
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visa färre...
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- Methods to study in vivo gastro intestinal (GI) transit and/or regional absorption of pharmaceuticals are available and increasingly used in drug development. A modelling approach to utilize the information generated in such studies for prospective predictions of absorption from newly developed modified release formulations was outlined and tested for the investigational drug AZD0837. This work was a natural extension to the companion article “A semi-mechanistic model to link in vitro and in vivo drug release for modified release formulations”. The drug release model governed the amount of substance released in distinct GI regions over time. GI distribution of released drug substance, region specific rate and extent of absorption and the influence of concomitant food intake were estimated with the model. The model was informed by data from a magnetic marker monitoring study and an intubation study with local administration in colon. Disposition estimates were further supported by observations following administration of oral solution and intravenous infusion of AZD0837. Distinctly different absorption properties were characterized for different GI regions. Bioavailability over the gut-wall was estimated to be high for substance released in the stomach and absorbed in duodenum (70%) compared to substance released and absorbed in the small intestine (25%). Bioavailability was once again higher in colon (70%) but on the other hand considerably slower than in the earlier parts of the GI tract. The established model was largely successful in predicting plasma concentration following administration of three newly developed formulations for which no clinical data had been applied during model building.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- Modified release
- IVIVC
- Magnetic marker monitoring
- Mechanistic modeling
- NONMEM
- Other pharmacy
- Övrig farmaci
- Pharmacokinetics and Drug Therapy
- Farmakokinetik och läkemedelsterapi
Publikations- och innehållstyp
- vet (ämneskategori)
- art (ämneskategori)
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