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Abstract #1583

Elucidating Subcutaneous Depot Formation and Release of the Injectable Anti-Diabetics Taspoglutide in Rats Using in vivo MRI

Basil Knnecke1, Andreas Bruns1, Olaf Kuhlmann2

1Behavioural Pharmacology & Preclinical Imaging, F. Hoffmann-La Roche Ltd, Basel, Switzerland; 2Non-Clinical Safety, F. Hoffmann-La Roche Ltd, Basel, Switzerland

Subcutaneous injection is an established route of administration for pharmacological interventions but the interaction of the drugs fate at the injection site and the ensuing pharmacokinetics has largely remained unexplored. Here, in vivo MRI was used to address this question for the peptidic anti-diabetic agent taspoglutide with the aim of providing a mechanistic rationale for the complex pharmacokinetics observed for its sustained release formulation. Different injection conditions were compared for their performance in a rat model of type 2 diabetes. MRI yielded estimates of depot formation and dissolution that were related to the pharmacokinetics of taspoglutide.