Mass Spectrometry Imaging Demonstrates the Regional Brain Distribution Patterns of Three First-Line Antiretroviral Drugs
| Autor: | Hendrik G. Kruger, Sanil D. Singh, Thavendran Govender, Sipho Mdanda, Tricia Naicker, Sooraj Baijnath, Sphamandla Ntshangase |
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| Rok vydání: | 2019 |
| Předmět: |
Drug
Efavirenz business.industry General Chemical Engineering media_common.quotation_subject Central nervous system virus diseases General Chemistry Pharmacology Corpus callosum Emtricitabine Article Mass spectrometry imaging Chemistry chemistry.chemical_compound medicine.anatomical_structure chemistry Pharmacokinetics Distribution (pharmacology) Medicine business QD1-999 medicine.drug media_common |
| Zdroj: | ACS Omega, Vol 4, Iss 25, Pp 21169-21177 (2019) ACS Omega |
| ISSN: | 2470-1343 |
| DOI: | 10.1021/acsomega.9b02582 |
| Popis: | HIV in the central nervous system (CNS) contributes to the development of HIV-associated neurological disorders (HAND), even with chronic antiretroviral therapy. In order for antiretroviral therapy to be effective in protecting the CNS, these drugs should have the ability to localize in brain areas known to be affected by HIV. Consequently, this study aimed to investigate the localization patterns of three first-line antiretroviral drugs, namely, efavirenz, tenofovir, and emtricitabine, in the rat brain. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) and matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) were utilized to assess the pharmacokinetics and brain spatial distribution of the three drugs. Each drug was administered (50 mg/kg) to healthy female Sprague–Dawley rats via intraperitoneal administration. LC–MS/MS results showed that all three drugs could be delivered into the brain, although they varied in blood–brain barrier permeability. MALDI-MSI showed a high degree of efavirenz localization across the entire brain, while tenofovir localized mainly in the cortex. Emtricitabine distributed heterogeneously mainly in the thalamus, corpus callosum, and hypothalamus. This study showed that efavirenz, tenofovir, and emtricitabine might be a potential drug combination antiretroviral therapy for CNS protection against HAND. |
| Databáze: | OpenAIRE |
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