Multiparametric magnetic resonance imaging to characterize cabotegravir long-acting formulation depot kinetics in healthy adult volunteers.
Beat M Jucker, Edward J Fuchs, Sarah Lee, Valeriu Damian, Paul Galette, Robert Janiczek, Katarzyna J Macura, Michael A Jacobs, Ethel D Weld, Meiyappan Solaiyappan, Ronald D'Amico, Jafar Sadik Shaik, Kalpana Bakshi, Kelong Han, Susan Ford, David Margolis, William Spreen, Manish K Gupta, Craig W Hendrix, Parul Patel
Author Information
Beat M Jucker: GlaxoSmithKline, Collegeville, PA, USA.
Edward J Fuchs: Departments of Internal Medicine and Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Sarah Lee: Amallis Consulting Ltd, London, UK.
Valeriu Damian: GlaxoSmithKline, Collegeville, PA, USA.
Paul Galette: GlaxoSmithKline, Collegeville, PA, USA.
Robert Janiczek: GlaxoSmithKline, Collegeville, PA, USA.
Katarzyna J Macura: Departments of Internal Medicine and Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Michael A Jacobs: Departments of Internal Medicine and Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Ethel D Weld: Departments of Internal Medicine and Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Meiyappan Solaiyappan: Departments of Internal Medicine and Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Ronald D'Amico: ViiV Healthcare, Research Triangle Park, NC, USA.
Jafar Sadik Shaik: GlaxoSmithKline, Collegeville, PA, USA.
Kalpana Bakshi: GlaxoSmithKline, Collegeville, PA, USA.
Kelong Han: GlaxoSmithKline, Collegeville, PA, USA.
Susan Ford: GlaxoSmithKline, Research Triangle Park, NC, USA.
David Margolis: ViiV Healthcare, Research Triangle Park, NC, USA.
William Spreen: ViiV Healthcare, Research Triangle Park, NC, USA.
Manish K Gupta: GlaxoSmithKline, Collegeville, PA, USA.
Craig W Hendrix: Departments of Internal Medicine and Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Parul Patel: ViiV Healthcare, Research Triangle Park, NC, USA.
AIM: Cabotegravir long-acting (LA) intramuscular (IM) injection is being investigated for HIV preexposure prophylaxis due to its potent antiretroviral activity and infrequent dosing requirement. A subset of healthy adult volunteers participating in a Phase I study assessing cabotegravir tissue pharmacokinetics underwent serial magnetic resonance imaging (MRI) to assess drug depot localization and kinetics following a single cabotegravir LA IM targeted injection. METHODS: Eight participants (four men, four women) were administered cabotegravir LA 600 mg under ultrasonographic-guided injection targeting the gluteal muscles. MRI was performed to determine injection-site location in gluteal muscle (IM), subcutaneous (SC) adipose tissue and combined IM/SC compartments, and to quantify drug depot characteristics, including volume and surface area, on Days 1 (≤2 hours postinjection), 3 and 8. Linear regression analysis examined correlations between MRI-derived parameters and plasma cabotegravir exposure metrics, including maximum observed concentration (C ) and partial area under the concentration-time curve (AUC) through Weeks 4 and 8. RESULTS: Cabotegravir LA depot locations varied by participant and were identified in the IM compartment (n = 2), combined IM/SC compartments (n = 4), SC compartment (n = 1) and retroperitoneal cavity (n = 1). Although several MRI parameter and exposure metric correlations were determined, total depot surface area on Day 1 strongly correlated with plasma cabotegravir concentration at Days 3 and 8, C and partial AUC through Weeks 4 and 8. CONCLUSION: MRI clearly delineated cabotegravir LA injection-site location and depot kinetics in healthy adults. Although injection-site variability was observed, drug depot surface area correlated with both plasma C and partial AUC independently of anatomical distribution.
