The pig as a preclinical model for predicting oral bioavailability and in vivo performance of pharmaceutical oral dosage forms: a PEARRL review.

Autor: Henze LJ; School of Pharmacy, University College Cork, Cork, Ireland., Koehl NJ; School of Pharmacy, University College Cork, Cork, Ireland., O'Shea JP; School of Pharmacy, University College Cork, Cork, Ireland., Kostewicz ES; Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany., Holm R; Drug Product Development, Janssen Research and Development, Johnson & Johnson, Beerse, Belgium., Griffin BT; School of Pharmacy, University College Cork, Cork, Ireland.
Jazyk: angličtina
Zdroj: The Journal of pharmacy and pharmacology [J Pharm Pharmacol] 2019 Apr; Vol. 71 (4), pp. 581-602. Date of Electronic Publication: 2018 Apr 10.
DOI: 10.1111/jphp.12912
Abstrakt: Objectives: In pharmaceutical drug development, preclinical tests in animal models are essential to demonstrate whether the new drug is orally bioavailable and to gain a first insight into in vivo pharmacokinetic parameters that can subsequently be used to predict human values. Despite significant advances in the development of bio-predictive in vitro models and increasing ethical expectations for reducing the number of animals used for research purposes, there is still a need for appropriately selected pre-clinical in vivo testing to provide guidance on the decision to progress to testing in humans. The selection of the appropriate animal models is essential both to maximise the learning that can be obtained from such experiments and to avoid unnecessary testing in a range of species.
Key Findings: The present review, provides an insight into the suitability of the pig model for predicting oral bioavailability in humans, by comparing the conditions in the GIT. It also contains a comparison between the bioavailability of compounds dosed to both humans and pigs, to provide an insight into the relative correlation and examples on why a lack of correlation may be observed.
Summary: While there is a general trend towards predicting human bioavailability from pig data, there is considerable variability in the data set, most likely reflecting species specific differences in individual drug metabolism. Nonetheless, the correlation between pigs vs. humans was comparable to that reported for dogs vs. humans. The presented data demonstrate the suitability of the pig as a preclinical model to predict bioavailability in human.
(© 2018 Royal Pharmaceutical Society.)
Databáze: MEDLINE
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