TABLE 1

CNS uptake of [3H]3TC ([14C]mannitol corrected) in the absence and presence of additional anti-HIV NRTIs

Results from 20 min [3H]3TC/[14C]mannitol perfusions in the absence (control) and presence of 50 μM 3TC, and 10-min [3H]3TC/[14C]mannitol-free preperfusions followed by 10-min [3H]3TC/[14C]mannitol perfusions in the absence (control) and presence of abacavir, AZT, d4T, and ddl, n = 3 to 5. Uptake of [3H]3TC in the absence and presence of unlabeled 3TC did not significantly differ (t test, p > 0.05). Furthermore, [3H]3TC uptake was not significantly altered in the presence of additional drugs (one-way ANOVA and Kruskal-Wallis one-way ANOVA as appropriate, p > 0.05).

In Situ Brain Perfusion Conditions
Brain Uptake
CSF Uptake
Choroid Plexus Uptake
ml / 100 g ml / 100 ml ml / 100 g
Control (20 min) 0.30 ± 0.05 0.63 ± 0.08 40.66 ± 5.54
+ 3TC 50 μM 0.28 ± 0.05 1.14 ± 0.19 24.31 ± 5.49
Control (10 + 10 min) 0.14 ± 0.07 0.6 ± 0.3 36.5 ± 5.8
+ Abacavir 100 μM 0.05 ± 0.03 0.8 ± 0.2 25.9 ± 5.1
6.8 μM 0.07 ± 0.04 1.1 ± 0.6 26.8 ± 3.0
+ AZT 100 μM 0.26 ± 0.03 0.9 ± 0.3 31.7 ± 5.6
7.1 μM 0.09 ± 0.03 0.7 ± 0.3 21.5 ± 6.1
+ d4T 100 μM 0.17 ± 0.04 0.4 ± 0.1 24.0 ± 2.8
3.1 μM 0.01 ± 0.01 1.6 ± 0.5 33.4 ± 3.9
+ ddl 100 μM 0.08 ± 0.03 0.3 ± 0.1 19.6 ± 3.3
2.2 μM
0.08 ± 0.02
0.7 ± 0.4
32.8 ± 3.6