Connecting Rodent and Human Pharmacokinetic Models for the Design and Translation of Glucose-Responsive Insulin.

Diabetes
Jing Fan YangMichael S Strano

Abstract

Despite considerable progress, development of glucose-responsive insulins (GRIs) still largely depends on empirical knowledge and tedious experimentation-especially on rodents. To assist the rational design and clinical translation of the therapeutic, we present a Pharmacokinetic Algorithm Mapping GRI Efficacies in Rodents and Humans (PAMERAH) built upon our previous human model. PAMERAH constitutes a framework for predicting the therapeutic efficacy of a GRI candidate from its user-specified mechanism of action, kinetics, and dosage, which we show is accurate when checked against data from experiments and literature. Results from simulated glucose clamps also agree quantitatively with recent GRI publications. We demonstrate that the model can be used to explore the vast number of permutations constituting the GRI parameter space and thereby identify the optimal design ranges that yield desired performance. A design guide aside, PAMERAH more importantly can facilitate GRI's clinical translation by connecting each candidate's efficacies in rats, mice, and humans. The resultant mapping helps to find GRIs that appear promising in rodents but underperform in humans (i.e., false positives). Conversely, it also allows for the discove...Continue Reading

References

Sep 1, 1979·The American Journal of Physiology·R A DeFronzoR Andres
May 1, 1987·The Journal of Clinical Investigation·L RossettiR A DeFronzo
Mar 4, 2003·Nature Reviews. Drug Discovery·Han van de Waterbeemd, Eric Gifford
Apr 28, 2005·Diabetes Care·UNKNOWN Workgroup on Hypoglycemia, American Diabetes Association
Apr 28, 2006·Clinical Pharmacokinetics·Hannah M JonesThierry Lavé
Oct 13, 2006·JAMA : the Journal of the American Medical Association·Daniel G Hackam, Donald A Redelmeier
Dec 19, 2006·BMJ : British Medical Journal·Pablo PerelKhalid S Khan
Oct 12, 2007·IEEE Transactions on Bio-medical Engineering·Chiara Dalla ManClaudio Cobelli
Jul 22, 2008·Physiological Measurement·Roman HovorkaMalgorzata E Wilinska
May 1, 2007·Journal of Diabetes Science and Technology·Anirban Roy, Robert S Parker
Feb 11, 2010·Journal of Diabetes Science and Technology·Stephen D PatekHoward Zisser
Apr 3, 2010·PLoS Medicine·H Bart van der WorpMalcolm R Macleod
Jan 1, 2009·IEEE Reviews in Biomedical Engineering·Claudio CobelliBoris P Kovatchev
Feb 9, 2012·Diabetic Medicine : a Journal of the British Diabetic Association·M PeyrotP-M Schumm-Draeger
Mar 1, 2012·Nature Reviews. Endocrinology·John C Pickup
Feb 7, 2013·Pharmacological Reviews·Hywel D WilliamsChristopher J H Porter
Aug 16, 2013·CPT: Pharmacometrics & Systems Pharmacology·Hm Jones, K Rowland-Yeo
Aug 16, 2013·CPT: Pharmacometrics & Systems Pharmacology·S SchallerT Eissing
Aug 1, 2014·Advanced Healthcare Materials·Gili BiskerMichael S Strano
Aug 2, 2014·Nature Reviews. Drug Discovery·Stacy R LindborgStephen J Ruberg
Nov 29, 2014·Nature Reviews. Drug Discovery·Omid VeisehRobert Langer
Feb 13, 2015·Proceedings of the National Academy of Sciences of the United States of America·Danny Hung-Chieh ChouDaniel G Anderson
Oct 24, 2015·Medical & Biological Engineering & Computing·O VahidiF K Knop
Nov 10, 2015·IEEE Transactions on Bio-medical Engineering·Stephan SchallerThomas Eissing
Mar 19, 2016·Nature Reviews. Drug Discovery·Alexander N ZaykovRichard D DiMarchi
Oct 5, 2016·Journal of the Mechanical Behavior of Biomedical Materials·A D Drozdov, J deC Christiansen
Aug 26, 2017·Advanced Healthcare Materials·Naveed A BakhMichael S Strano
Sep 25, 2017·Nature Chemistry·Naveed A BakhMichael S Strano
Sep 30, 2017·CPT: Pharmacometrics & Systems Pharmacology·Oskar AlskärMaria C Kjellsson
Nov 4, 2017·Diabetes·Niels C KaarsholmDavid E Kelley
Dec 5, 2017·Science Advances·Akira MatsumotoTakayoshi Suganami
Dec 14, 2017·Journal of Pharmacokinetics and Pharmacodynamics·Christoph NiederaltJörg Lippert
Mar 24, 2018·Diabetes Care·UNKNOWN American Diabetes Association
Aug 21, 2018·Clinical Pharmacology and Therapeutics·Alexander W KrugMarian Iwamoto
Jan 4, 2019·Advanced Healthcare Materials·Michael A VandenBerg, Matthew J Webber

❮ Previous
Next ❯

Citations

Jul 22, 2020·Diabetes·Simeon I Taylor, Richard D DiMarchi
Mar 13, 2021·Diabetologia·Mark A JarosinskiMichael A Weiss
Nov 3, 2020·Molecular Metabolism·Thomas Hoeg-Jensen
Apr 19, 2021·Diabetes Research and Clinical Practice·Tim Heise

❮ Previous
Next ❯

Related Concepts

Related Feeds

American Diabetes Association Journals

Discover the latest diabetes research published by the journals from the American Diabetes Association.