The role of the blood-brain and blood-cerebrospinal fluid (CSF) barriers in the distribution of anti-human immunodeficiency virus (HIV) drugs is integral to the design of effective treatment regimens for
HIV infection within the brain.
Abacavir (formerly
1592U89) is a
nucleoside analog reverse transcriptase inhibitor, which has activity against HIV. The ability of this
drug to reach the brain at therapeutic concentrations has been explored by means of an established bilateral in situ brain perfusion model in combination with high-performance liquid chromatography analysis in the anesthetized guinea pig. The influence of other drugs on the entry of
abacavir into the brain was also investigated and is of special significance with the use of three of more
anti-HIV drugs as the recommended treatment for
HIV infection. The results of this study indicate that intact [(14)C]
abacavir can cross the blood-brain and blood-CSF barriers and enter the brain and cisternal CSF. Further studies, at a perfusion time of 10 min, revealed that the uptake (R(cerebrum)) of this (14)C-labeled
drug (10.1 +/- 0.6%) was not affected by the presence of 0.86 to 200 microM unlabeled
abacavir (6.8 microM; 11.0 +/- 1.4%), the
nucleoside transport inhibitor [10 microM 6-(4-nitrobenzyl)thio-9-beta-D-ribofuranosylpurine; 9.7 +/- 3.3%], or a substrate for the nucleobase transporter (100 microM
adenine; 12.7 +/- 3.0%). This would suggest that the entry of
abacavir into the brain would not be affected by the presence of other
anti-HIV drugs. The results of this animal study indicate that
abacavir would be a useful addition to a treatment regimen against
HIV-infection within the brain.