Optimization of pig models for translation of subcutaneous pharmacokinetics of therapeutic proteins: Liraglutide, insulin aspart and insulin detemir

Prediction of human pharmacokinetics (PK) from data obtained in animal studies is essential in drug development. Here, we present a thorough examination of how to achieve good pharmacokinetic data from the pig model for translational purposes by using single-species allometric scaling for selected t...

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Bibliographic Details
Published in:Translational research : the journal of laboratory and clinical medicine 2022-01, Vol.239, p.71-84
Main Authors: Pedersen, Karen-Margrethe, Gradel, Anna Katrina Jógvansdóttir, Ludvigsen, Trine Pagh, Christoffersen, Berit Østergaard, Fuglsang-Damgaard, Caroline Amalie, Bendtsen, Kristian Moss, Madsen, Suzi Høgh, Manfé, Valentina, Refsgaard, Hanne Hoffmann Frølund
Format: Article
Language:English
Subjects:
Animals
Humans
Injections, Intravenous
Injections, Subcutaneous
Insulin Aspart - administration & dosage
Insulin Aspart - pharmacokinetics
Insulin Detemir - administration & dosage
Insulin Detemir - pharmacokinetics
Liraglutide - administration & dosage
Liraglutide - pharmacokinetics
Sus scrofa
Swine
Swine, Miniature
Translational Research, Biomedical
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Summary:Prediction of human pharmacokinetics (PK) from data obtained in animal studies is essential in drug development. Here, we present a thorough examination of how to achieve good pharmacokinetic data from the pig model for translational purposes by using single-species allometric scaling for selected therapeutic proteins: liraglutide, insulin aspart and insulin detemir. The predictions were based on non-compartmental analysis of intravenous and subcutaneous PK data obtained from two injection regions (neck, thigh) in two pig breeds, domestic pig and Göttingen Minipig, that were compared with PK parameters reported in humans. The effects of pig breed, injection site and injection depth (insulin aspart only) on the PK of these proteins were also assessed. Results show that the prediction error for human PK was within two-fold for most PK parameters in both pig breeds. Furthermore, pig breed significantly influenced the plasma half-life and mean absorption time (MAT), both being longer in Göttingen Minipigs compared to domestic pigs (P
ISSN:1931-5244
1878-1810
DOI:10.1016/j.trsl.2021.08.005