1015-P: Insulin-Excipient–Induced Inflammation and Pharmacokinetic Variability

Abstract

Objective: To evaluate the impact of phenol-based insulin-excipient induced inflammation on insulin pharmacokinetic (PK) variability in diabetic mice and to evaluate effects of anti-inflammatory agents (dexamethasone and cromolyn) in minimizing excipient induced inflammation. Methods: Using a modified murine air pouch model, saline or insulin excipients were continuously infused for durations of 1 and 3 days. Subsequently, a single subcutaneous insulin injection of 0.3U (1:100; Humalog) was placed into the air pouch. Blood samples were taken periodically. Bioanalysis was done by ELISA for PK evaluation. A separate analysis determined effects of anti-inflammatory agents co-infused with insulin on maintaining glycemia during infusion pump therapy while extending its lifespan. Tissue was analyzed by standard histopathology (H and E). Results: Primary PK values Cmax, Tmax, AUC (0-120) for saline and excipient infused groups are depicted in Figure 1A and 1B. The excipient group demonstrated lower Tmax, AUC (0-120) and Cmax as compared to saline group. Figure 1C depicts a significantly greater degree of inflammation in all excipient treated groups. Usage of co-infusion with anti-inflammatory agents extends insulin infusion set lifespan. Conclusion: Insulin excipients induce site specific inflammation that alters insulin PK and diminishes the in vivo insulin bioavailability. Confirmation in a porcine model is underway. Disclosure M.K. Hidau: None. C. Kesserwan: None. Y. Qiao: None. D. Kreutzer: Other Relationship; Self; Abbott Laboratories, cell and molecualar tissue enginnering (cmte). U. Klueh: Research Support; Self; Abbott. Other Relationship; Self; Cell and Molecular Tissue Engineering, LLC. Funding The Leona M. and Harry B. Helmsley Charitable Trust