Multiparametric magnetic resonance imaging to characterize cabotegravir long‐acting formulation depot kinetics in healthy adult volunteers
Open Access
- 31 July 2021
- journal article
- research article
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 88 (4), 1655-1666
- https://doi.org/10.1111/bcp.14977
Abstract
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 (Cmax) 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, Cmax 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 Cmax and partial AUC independently of anatomical distribution.Funding Information
- ViiV Healthcare
This publication has 38 references indexed in Scilit:
- Long-acting injectable antiretrovirals for HIV treatment and preventionCurrent Opinion in HIV and AIDS, 2013
- Improving the Success Rate of Gluteal Intramuscular InjectionsPancreas, 2013
- Effect of particle size on the dissolution behaviors of poorly water-soluble drugsArchives of Pharmacal Research, 2012
- Magnetic resonance imaging of tablet dissolutionEuropean Journal of Pharmaceutics and Biopharmaceutics, 2010
- Critical Factors Influencing the In Vivo Performance of Long-acting Lipophilic Solutions—Impact on In Vitro Release Method DesignThe AAPS Journal, 2009
- Role ofin vitrorelease models in formulation development and quality control of parenteral depotsExpert Opinion on Drug Delivery, 2009
- A comparative study at 3 T of sequence dependence of T2 quantitation in the kneeMagnetic Resonance Imaging, 2008
- Intramuscular injections into the buttocks: Are they truly intramuscular?European Journal of Radiology, 2006
- 19F-magnetic resonance spectroscopy and chemical shift imaging for schizophrenic patients using haloperidol decanoatePsychiatry and Clinical Neurosciences, 2002
- MR appearance of intramuscular injections.American Journal of Roentgenology, 1992