Pharmacokinetics of a Long-Acting Nanoformulated Dolutegravir Prodrug in Rhesus Macaques
Open accessAbstract
A nanoformulated myristoylated dolutegravir prodrug (NMDTG) was prepared using good laboratory practice protocols. Intramuscular injection of NMDTG (118 ± 8 mg/ml, 25.5 mg of DTG equivalents/kg of body weight) to three rhesus macaques led to plasma DTG levels of 86 ± 12 and 28 ± 1 ng/ml on days 35 and 91, respectively. The NMDTG platform showed no significant adverse events. Further modification may further extend the drug's apparent half-life for human use.
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In rhesus macaques, prodrug nanoparticles maintained therapeutic concentrations of dolutegravir for ~40 days and extended the half-life of dolutegravir to ~19.5 days.
“In rhesus macaques, prodrug nanoparticles maintained therapeutic concentrations of dolutegravir for ~40 days and extended the half-life of dolutegravir to ~19.5 days.”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [18]
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- Authors
- McMillan, J., Szlachetka, A., Slack, L., Sillman, B., Lamberty, B., Morsey, B., Callen, S., Gautam, N., Alnouti, Y., Edagwa, B., Gendelman, H. E., & Fox, H. S.
- Affiliations
- University of Nebraska Medical Center (US)
- Corresponding author
- McMillan, JoEllyn
- Gendelman, Howard E.
- ORCID
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2018-01
- Volume
- 62
- Issue
- 1
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC5740312
- OpenAlex
- W2766546877
- Cited by
- 32
- References
- 29
- Citations by year
- 2025: 3 · 2024: 4 · 2022: 5 · 2021: 2 · 2020: 6 · 2019: 7 · 2018: 5
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- HHS | National Institutes of Health (R01MH104147, R01NS036126, 2R01NS034239, P01MH64570, R01AG043540, P01DA028555, P30MH062261)
- Topics
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- dolutegravir, nanoformulations, pharmacokinetics, rhesus monkeys, intramuscular injection, antiretroviral drugs, drug half-life extension, adverse events
- MeSH terms
- Dolutegravir, Animals, Delayed-Action Preparations, Heterocyclic Compounds, 3-Ring, Injections, Intramuscular, Macaca mulatta, Male, Oxazines, Piperazines, Prodrugs, Pyridones, HIV Integrase Inhibitors, Nanocomposites
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