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Jucker BM, Fuchs EJ, Lee S, et al. Multiparametric magnetic resonance imaging to characterize cabotegravir long-acting formulation depot kinetics in healthy adult volunteers. Br J Clin Pharmacol. 2021;doi: 10.1111/bcp.14977.
Jucker, B. M., Fuchs, E. J., Lee, S., Damian, V., Galette, P., Janiczek, R., Macura, K. J., Jacobs, M. A., Weld, E. D., Solaiyappan, M., D'Amico, R., Shaik, J. S., Bakshi, K., Han, K., Ford, S., Margolis, D., Spreen, W., Gupta, M. K., Hendrix, C. W., & Patel, P. (2021). Multiparametric magnetic resonance imaging to characterize cabotegravir long-acting formulation depot kinetics in healthy adult volunteers. British journal of clinical pharmacology, . https://doi.org/10.1111/bcp.14977
Jucker, Beat M, et al. "Multiparametric magnetic resonance imaging to characterize cabotegravir long-acting formulation depot kinetics in healthy adult volunteers." British journal of clinical pharmacology vol. (2021). doi: https://doi.org/10.1111/bcp.14977
Jucker BM, Fuchs EJ, Lee S, Damian V, Galette P, Janiczek R, Macura KJ, Jacobs MA, Weld ED, Solaiyappan M, D'Amico R, Shaik JS, Bakshi K, Han K, Ford S, Margolis D, Spreen W, Gupta MK, Hendrix CW, Patel P. Multiparametric magnetic resonance imaging to characterize cabotegravir long-acting formulation depot kinetics in healthy adult volunteers. Br J Clin Pharmacol. 2021 Jul 08; doi: 10.1111/bcp.14977. Epub 2021 Jul 08. PMID: 34240449.
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Br J Clin Pharmacol. 2021 Jul 08; doi: 10.1111/bcp.14977. Epub 2021 Jul 08.

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

British journal of clinical pharmacology

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

Affiliations

  1. GlaxoSmithKline, Collegeville, PA, USA.
  2. Departments of Internal Medicine and Radiology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
  3. Amallis Consulting Ltd, London, UK.
  4. ViiV Healthcare, Research Triangle Park, NC, USA.
  5. GlaxoSmithKline, Research Triangle Park, NC, USA.

PMID: 34240449 DOI: 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 (C

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

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

© 2021 ViiV Healthcare. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Keywords: HIV/AIDS; MRI; antiretrovirals; cabotegravir; pharmacokinetics-pharmacodynamic

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