Abstract #3213

Serial MRI to Assess Effects of Drug Particle Size on Inflammation and Pharmacokinetics to Support Development of Long Acting Parenteral Formulations

Stephen Lenhard¹, Mary Rambo¹, Tracy Gales², Taki Kambara³, Cindy Fishman³, Valeriu Damian⁴, Nima Akhavein⁵, Matt Burke⁵, and Beat Jucker¹

¹Bioimaging, GlaxoSmithKline, Collegeville, PA, United States, ²Histology, GlaxoSmithKline, Collegeville, PA, United States, ³Pathology, GlaxoSmithKline, Collegeville, PA, United States, ⁴Modeling and Translational Biology, GlaxoSmithKline, Collegeville, PA, United States, ⁵Drug Delivery, GlaxoSmithKline, Collegeville, PA, United States

We evaluated the effect of Long Acting Parenteral particle size on drug depot kinetics and inflammation using ultra small paramagnetic iron oxide (USPIO) T2W MRI. Our results showed an immediate post injection difference in inflammatory response and histological confirmation of greater muscle injury in the smaller micronized (1um) particle group compared to larger 20um particle formulation. The imaging of the drug depot in vivo with MRI combined with drug PK, tissue biodistribution, and histology allows for the development of individual Physiological Based PK models of drug biodistribution which would add significant scientific value to drug development.

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