Low blood-brain barrier permeability to azidothymidine (AZT), 3TC, and thymidine in the rat.
The blood-brain barrier (BBB) permeability to [3H]-azidodeoxythymidine (AZT), deoxythiacytidine (3TC), 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 [14C]-sucrose as a plasma volume marker. The brain volumes of distribution (VD) 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.
Wu
D
D
Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Clement
J G
JG
Pardridge
W M
WM
D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D019259:Lamivudine / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000493:pharmacokinetics*; D015215:Zidovudine / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D019259:Lamivudine; D015215:Zidovudine; D013936:Thymidine