Abstract
As the HIV epidemic continues to contribute to global morbidity and mortality, the prevalence of HIV-associated neurological disorders (HAND) also continues to be a major concern in infected individuals, despite the widespread use of combination antiretroviral therapy. Therefore, current antiretroviral drugs should be able to reach therapeutic levels in the brain for the treatment of HAND. The brain distribution of the next-generation non-nucleoside reverse transcriptase inhibitor, rilpivirine (RPV) was investigated in healthy female Sprague-Dawley (SD) rats. The presented study involves the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) to estimate the concentrations of RPV in plasma and brain homogenate samples. The use of matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) provided regional spatial distribution of RPV in brain tissue sections. The localization of RPV was found to be relatively high in the hypothalamus, thalamus and corpus callosum, brain regions known to be associated with neurodegeneration during HAND (including the cerebral cortex). This study has shown that RPV has an excellent blood-brain barrier penetrability. Thus, in combination with other antiretroviral drugs, better central nervous system (CNS) protection against HAND can possibly be achieved.
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