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Publication
Enterically delivered insulin tregopil exhibits rapid absorption characteristics
and a pharmacodynamic effect similar to human insulin in conscious dogs.
Authors Gregory JM, Lautz M, Moore LM, Williams PE, Reddy P, Cherrington AD
Submitted By Submitted Externally on 12/12/2018
Status Published
Journal Diabetes, obesity & metabolism
Year 2019
Date Published 1/1/2019
Volume : Pages 21 : 160 - 169
PubMed Reference 30095210
Abstract Current therapy fails to emulate rapid (first-phase) insulin release in relation
to a meal, a key defect in types 1 and 2 diabetes. We aimed to quantify the
pharmacokinetic (PK) and pharmacodynamic (PD) profile of insulin tregopil, an
enterically-absorbed insulin analog that restores the normal distribution of
insulin between the hepatic portal and peripheral circulations., The PK and PD
profiles of insulin tregopil were studied in overnight-fasted, catheterized,
conscious canines using four approaches: (1) equimolar intraportal infusions of
tregopil vs human insulin; (2) escalating doses of oral tregopil; (3) identical,
consecutive enteric doses of tregopil; and (4) comparison of oral tregopil to
inhaled and subcutaneous human insulin administration., Equimolar intraportal
infusions of tregopil and human insulin resulted in very similar PK profiles and
PD profiles were nearly identical. Enteric delivery of tregopil brought about
rapid absorption with tmax = 20 minutes in most cases. Median tmax was 20
minutes for oral tregopil and inhaled insulin and 88 minutes for subcutaneous
human insulin. The time required for arterial plasma insulin levels to return to
baseline was approximately 90, 210 and 360 minutes for oral tregopil, inhaled
insulin and subcutaneous insulin, respectively., Enterically delivered tregopil
is rapidly absorbed and restores a portal-to-peripheral vascular distribution.
These characteristics should improve postprandial hyperglycaemia in types 1 and
2 diabetes.




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