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Journal article
Exploring the Interaction Between Injection Site and Biological Sex on the Real-world Population Pharmacokinetics of Long-acting Cabotegravir and Rilpivirine in People With HIV
Open forum infectious diseases, Vol.12(10), ofaf614
2025
PMID: 41141445
Abstract
Long-acting injectable antiretroviral therapy with cabotegravir and rilpivirine is efficacious though demonstrates large interindividual variability in systemic drug exposure. To better understand the influences of injection and individual factors on drug exposure in a "real-world" population, we constructed a population pharmacokinetic model using data from people with HIV-1 in an outpatient clinic setting.
We conducted a prospective noninterventional study assessing injected cabotegravir and rilpivirine disposition within the Royal Perth Hospital HIV cohort over a 16-week period. Serum concentrations of cabotegravir and rilpivirine were measured using a validated liquid chromatography tandem mass spectrometry assay. Postinjection ultrasound measured the skin-to-muscle thickness and depot disposition (intramuscular or subcutaneous) following ventrogluteal injection. These data were incorporated into a population pharmacokinetic model.
Thirty-one individuals were recruited between October 2023 and March 2024. A total of 141 blood samples were collected with 134 unique injection site ultrasounds. Median trough concentrations were 1390 ng/mL for cabotegravir and 56.0 ng/mL for rilpivirine. Of 134 injections, 40 (30%) were primarily into subcutaneous tissue and occurred more commonly in women. A single-compartment model including absorption optimally described cabotegravir pharmacokinetics, with subcutaneous location of depots associated with a 56.3% reduction in absorption rate. Rilpivirine pharmacokinetics fitted optimally to a single compartment model including absorption, with no significant covariates identified.
Subcutaneous depot deposition after intramuscular injections is not uncommon, occurring more frequently in females and is associated with increased skin to muscle thickness. Slower absorption of cabotegravir from subcutaneous administration contributes to the observed sex differences in drug concentrations.
Details
- Title
- Exploring the Interaction Between Injection Site and Biological Sex on the Real-world Population Pharmacokinetics of Long-acting Cabotegravir and Rilpivirine in People With HIV
- Authors/Creators
- Benedict Tan - Pathwest Laboratory MedicineMina John - IIID, Medical Genomics, Murdoch University, Murdoch, Western AustraliaAlison Castley - Royal Perth HospitalLeah Williams - Royal Perth HospitalDavid Joyce - Pathwest Laboratory MedicineDavid Nolan - Royal Perth HospitalSean O'Halloran - Biochemistry, Toxicology and Pharmacology, PathWest, Nedlands, Western AustraliaSam Salman - The University of Western Australia
- Publication Details
- Open forum infectious diseases, Vol.12(10), ofaf614
- Publisher
- Oxford University Press on behalf of Infectious Diseases Society of America.
- Number of pages
- 9
- Identifiers
- 991005823549307891
- Copyright
- © The Author(s) 2025.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.23 Antibiotics & Antimicrobials
- 1.23.1680 Injection Safety
- Web Of Science research areas
- Immunology
- Infectious Diseases
- Microbiology
- ESI research areas
- Immunology