Multiparametric magnetic resonance imaging to characterize cabotegravir long‐acting formulation depot kinetics in healthy adult volunteers

• DOI: 10.1111/bcp.14977
• Publication Date: 2021-07-09T03:24:17Z
• Authors: Beat M. Jucker; Edward J. Fuchs; Sarah Lee; Valeriu Damian; Paul Galette; Robert Janiczek; Katarzyna J. Macura; Michael A. Jacobs; Ethel D. Weld; Meiyappan Solaiya...; Ronald D'Amico; Jafar Sadik Shaik; Kalpana Bakshi; Kelong Han; Susan Ford; David Margolis; William Spreen; Manish K. Gupta; Craig W. Hendrix; Parul Patel
• Keywords: Depot

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) assess drug depot localization kinetics following single LA IM targeted injection. Methods Eight participants (four men, four women) were administered 600 mg under ultrasonographic‐guided targeting the gluteal muscles. MRI was performed determine injection‐site location muscle (IM), subcutaneous (SC) adipose combined IM/SC compartments, quantify characteristics, including volume surface area, on Days 1 (≤2 hours postinjection), 3 8. Linear regression analysis examined correlations between MRI‐derived parameters plasma exposure metrics, maximum observed concentration ( C max ) partial area concentration–time curve (AUC) through Weeks 4 Results locations varied by participant identified compartment n = 2), compartments 4), SC 1) retroperitoneal cavity 1). Although several parameter metric determined, total Day strongly correlated with at 8, AUC Conclusion clearly delineated adults. variability observed, both independently anatomical distribution.