T. Burt, D. C. Rouse, B. B. Chin, S. Chow, D. H. Weitzel, H. Wu, T. C. Hawk, M. Cohen-Wolkowiez, R. J. Noveck; Duke University, Durham, NC

BACKGROUND: Intra-Arterial Microdosing (IAM) is a novel drug development approach combining intra-arterial drug delivery with microdosing. We aimed to demonstrate that IAM leads to similar target exposure as systemic full-dose administration but with minimal systemic exposure.
METHODS: Insulin 0.34 IU/kg was administered intra-arterially (ipsilateral femoral artery) to 2 CD IGS rats just prior to 60-minute 18F-FDG uptake imaging of ipsilateral (leg), contralateral (leg), and systemic (spine) muscles. Area under the curve (AUC) was calculated by the linear trapezoidal method and together with maximum glucose uptake (Emax) were summarized by descriptive statistics.
RESULTS: Contralateral and systemic Emax (mean ±SD: 0.323 ±0.129 and 0.297 ±0.205, respectively) and AUC (mean ±SD: 13.08 ±8.12 and 13.39 ±10.78, respectively) post IAM were similar but lower than ipsilateral Emax and AUC (0.615 ±0.367 and 22.13 ±15.33, respectively; Figure).
CONCLUSION: Target exposure post IAM was similar to systemic full dose administration but with minimal systemic effects. Our findings are being validated in larger studies in animals and humans using different targets and classes of drugs. IAM could enable safe, inexpensive and early study of novel drugs at the first-in-man stage and the study of established drugs in vulnerable populations.