Bictegravir Plus Tenofovir Alafenamide Nanoformulation as a Long-Acting Pre-Exposure Prophylaxis Regimen: Application of Modeling to Design Non-Human Primate Pharmacokinetic Experiments.

ABSTRACT: Bictegravir (BIC) and tenofovir alafenamide fumarate (TAF), two potent anti-HIV drugs, had been nanoformulated (nBIC-TAF) to achieve once-a-month PrEP coverage. In-vivo mouse experiments for nBIC-TAF exhibited favorable subcutaneous (SC) pharmacokinetics. To probe the clinical suitability of the nBIC-TAF, as the next step, we intend to study nBIC-TAF in non-human primates (NHP), as the best preclinical model to foster clinical trials. Before entering an expensive NHP study, however, we seek to improve our a priori understanding about nBIC-TAF in higher species, having just mouse data. The mechanism-based pharmacokinetic modeling (MBPK) has been used as an appropriate method for pharmacokinetic modeling and interspecies scaling for nanoformulations.

SUBMITTER: Perazzolo S 

PROVIDER: S-EPMC7775496 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature