Mass spectrometric investigations into the brain delivery of abacavir, stavudine and didanosine in a rodent model
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−1 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 Cmax with concentration of 831.2, 1300 and 43.37 ngmL−1, 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 Cmax that was above the IC50 for HIV (457.6 and 112.0 ngmL−1, 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−1 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 Cmax with concentration of 831.2, 1300 and 43.37 ngmL−1, 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 Cmax that was above the IC50 for HIV (457.6 and 112.0 ngmL−1, 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.
