Effects Of Lymphocyte Trafficking on Antiretroviral Drug Distribution within the Lymph Node

Blocking lymphocyte entry into murine lymph node lobules increases intracellular concentrations of tenofovir and efavirenz, but not raltegravir, highlighting drug-specific intracellular equilibration effects.

• Why it matters: Spatial pharmacokinetic data suggest passive diffusion cannot fully explain antiretroviral levels in lymphoid tissues, leaving uncertainty about whether lymphocytes contribute as carriers.
• What they did: In mice, intravenous drug delivery was paired with antibody-mediated blockade of lymphocyte trafficking, and a mechanistic physiologically based pharmacokinetic model with plasma, PBMC, LN extracellular fluid, and LN intracellular space was simulated.
• The result: Simulations and experiments indicate that blocking trafficking expands LN extracellular fluid volume and can counterintuitively raise intracellular drug levels for drugs with slower equilibration, while rapidly equilibrating raltegravir remains unchanged.

AI summary of the abstract · may contain errors · not medical advice · read the paper.