Investigating time dependent brain distribution of nevirapine via mass spectrometric imaging
2019
Central nervous system (CNS) HIV infection causes brain tissue inflammation and tissue deficit that contributes to neuroAIDS. This complication is escalated by the blood–brain barrier (BBB), which prevents easy access to antiretroviral drugs entering the CNS. In this study the aims were to investigate the BBB membrane penetration and brain localization patterns of Nevirapine (NVP) using Imaging Mass Spectrometry (MSI). Sprague–Dawley rats received an intraperitoneal dose of NVP (50 mg kg−1). Plasma and brain samples were harvested, and mass spectrometric methods were then applied to determine the pharmacokinetic properties and localization patterns of NVP in the brain. The pharmacokinetic parameters demonstrated a rapid bio-distribution of NVP in plasma and brain. The plasma Cmax was 6320 ng mL−1 and the brain Cmax was 1923 ng mL−1, both at a Tmax of 0.25 h. MSI of coronal brain sections showed that NVP penetrated and localized in the brain regions implicated with the development of HIV associated neurodegeneration. NVP has great potential to combat neuroAIDS.
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