2008 - Marseille - France

PAGE 2008: Applications- Endocrine
Tae Han

Alteration of glucose and insulin regulatory networks for the treatment of type 2 diabetes mellitus

Tae H. Han1, Elizabeth M. Migoya1, Lata Maganti1, Rebecca Baillie2, Paul Brazhnik2, and James R. Bosley, Jr.2

1 Merck & Co Inc 2 Rosa Pharmaceuticals

A quantitative framework for the (patho)physiological mechanisms and pathways that underlie type 2 diabetes mellitus (T2D) was needed in order to characterize the pharmacological and toxicological attributes of single or multiple compound/target pairs.  The objective of this work was to develop an integrated pharmacokinetic and (patho)physiological based model that links relevant information from in vitro experiments, evaluations in non-clinical studies, and results from clinical studies.  In particular, a network of interactions that represents key attributes of T2D was generated and relevant parameter values were identified from literature and non-clinical assessments.  Virtual patients based on the disease state of the patients enrolled in Phase I studies were created with the goal of assessing the performance of altered glucose metabolism in late-stage clinical studies through trial simulation.  In conclusion, this model may serve as a basis to identify the impact of altered pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship to identify target populations for therapy and for lead optimization.

Reference: PAGE 17 (2008) Abstr 1375 [www.page-meeting.org/?abstract=1375]
Poster: Applications- Endocrine