Low blood-brain barrier permeability to azidothymidine (AZT), 3TC™ and thymidine in the rat

The blood-brain barrier (BBB) permeability to [H-3]-azidodeoxythymidine (AZT), deoxythiacytidine (3TC(TM)), and thymidine was studied using both an intravenous injection/external organ (IV/EO) method and an internal carotid artery perfusion (ICAP) technique in parallel with [C-14]-sucrose as a plasma volume marker. The brain volumes of distribution (V-D) of the three compounds approximated that of sucrose with either method. Although the lipid solubility of AZT, as determined by the 1-octanol/buffer partition coefficient (P), was 16-fold higher than that of thymidine, the BBB permeability-surface area (PS) products were almost identical, consistent with preferential efflux of AZT from brain to blood. (C) 1998 Published by Elsevier Science B.V.