Antiretroviral Penetration and Drug Transporter Concentrations in the Spleens of Three Preclinical Animal Models and Humans.

ABSTRACT: Adequate antiretroviral (ARV) concentrations in lymphoid tissues are critical for optimal antiretroviral therapy (ART). While the spleen contains 25% of the body's lymphocytes, there are minimal data on ARV penetration in this organ. This study quantified total and protein-unbound splenic ARV concentrations and determined whether drug transporters, sex, or infection status were modifiers of these concentrations in animal models and humans. Two humanized mice models (hu-HSC-Rag [n = 36; 18 HIV-positive (HIV⁺) and 18 HIV-negative (HIV^-)] and bone marrow-liver-thymus [n = 13; 7 HIV⁺ and 6 HIV^-]) and one nonhuman primate (NHP) model (rhesus macaque [n = 18; 10 SHIV⁺ and 8 SHIV^-]) were dosed to steady state w

SUBMITTER: Devanathan AS 

PROVIDER: S-EPMC7508597 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature