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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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