Mass spectrometric investigations into the brain delivery of abacavir, stavudine and didanosine in a rodent model
Creators: name: Sipho Mdanda
name: Sphamandla Ntshangase
name: Sanil D. Singh
name: Naicker, Tricia
name: Kruger, Hendrik G.
name: Sooraj Baijnath
name: Thavendran Govender
Publisher: name: Taylor & Francis
Year: 2019
Subjects: subject: Biophysics
subject: Biochemistry
subject: 29999 Physical Sciences not elsewhere classified
subject: FOS: Physical sciences
subject: FOS: Physical sciences
subject: Medicine
subject: Neuroscience
subject: Pharmacology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: 80699 Information Systems not elsewhere classified
subject: FOS: Computer and information sciences
subject: FOS: Computer and information sciences
subject: 111714 Mental Health
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: 110309 Infectious Diseases
subject: 60506 Virology

description: HIV replication in the brain is unopposed due to reduced antiretroviral drug penetration into the central nervous system (CNS). Prevalence of HIV-associated neurocognitive disorder (HAND) has increased severely in patients living with HIV despite current treatments. The aims of this study were to evaluate the brain bio-distribution of alternative nucleoside reverse transcriptase inhibitors, abacavir, stavudine and didanosine in the CNS and to determine their localization patterns in the brain.Sprague-Dawley rats received 50 mg kg<sup>−1</sup> single i.p dose of each drug. Mass spectrometric techniques were then used to investigate the pharmacokinetics and localization patterns of these drugs in the brain using LC-MS/MS and mass spectrometric imaging (MSI), respectively.Abacavir, stavudine and didanosine reached the Brain C<sub>max</sub> with concentration of 831.2, 1300 and 43.37 ngmL<sup>−1</sup>, respectively. Based on MSI analysis Abacavir and Stavudine were located in brain regions that are strongly implicated in the progression of HAND.Abacavir and Stavudine penetrated into CNS, reaching a C<sub>max</sub> that was above the IC<sub>50</sub> for HIV (457.6 and 112.0 ngmL<sup>−1</sup>, respectively), however, it was noted ddI showed poor entry within the brain, therefore, it is recommended that this drug cannot be considered for treating CNS-HIV. HIV replication in the brain is unopposed due to reduced antiretroviral drug penetration into the central nervous system (CNS). Prevalence of HIV-associated neurocognitive disorder (HAND) has increased severely in patients living with HIV despite current treatments. The aims of this study were to evaluate the brain bio-distribution of alternative nucleoside reverse transcriptase inhibitors, abacavir, stavudine and didanosine in the CNS and to determine their localization patterns in the brain. Sprague-Dawley rats received 50 mg kg<sup>−1</sup> single i.p dose of each drug. Mass spectrometric techniques were then used to investigate the pharmacokinetics and localization patterns of these drugs in the brain using LC-MS/MS and mass spectrometric imaging (MSI), respectively. Abacavir, stavudine and didanosine reached the Brain C<sub>max</sub> with concentration of 831.2, 1300 and 43.37 ngmL<sup>−1</sup>, respectively. Based on MSI analysis Abacavir and Stavudine were located in brain regions that are strongly implicated in the progression of HAND. Abacavir and Stavudine penetrated into CNS, reaching a C<sub>max</sub> that was above the IC<sub>50</sub> for HIV (457.6 and 112.0 ngmL<sup>−1</sup>, respectively), however, it was noted ddI showed poor entry within the brain, therefore, it is recommended that this drug cannot be considered for treating CNS-HIV.