An ultra-long-acting dimeric bictegravir prodrug defined by a short pharmacokinetic tail.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41565650.
- Also identified by DOI 10.1038/s41467-026-68501-5 and PMC identifier 12916993.
- Licence recorded as CC BY-NC-ND.
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Abstract
Ultra-long-acting (ULA) antiretroviral parenteral formulations, with low injection volumes, high resistance barriers, and short pharmacokinetic (PK) tails, can transform HIV-1 therapeutics. Here, we converted bictegravir (BIC), a potent daily oral antiretroviral drug, into monomeric and homodimeric ester prodrugs. The homodimeric prodrug nanosuspension, NMXBIC, shows sustained plasma BIC levels > 16 times the protein-adjusted 95% inhibitory concentration (PA-IC<sub>95</sub>) for six months after a single injection in Sprague Dawley rats. The results paralleled a short PK tail with the potential for late dose forgiveness. The monomeric prodrug nanosuspension, NM2BIC, shows lower year-long plasma BIC concentrations above PA-IC<sub>95</sub> after a single injection. After repeated injections, NMXBIC and NM2BIC are well tolerated in New Zealand White rabbits. NMXBIC's physicochemical properties and high BIC loading/unit mass of the prodrug contribute to its unique ULA PK profile. These results support its development as a ULA formulation for HIV-1 treatment and prevention.
Medical subject headings
- Prodrugs
- Heterocyclic Compounds, 4 or More Rings
- Anti-HIV Agents