Document 0062
 DOCN  M9490062
 TI    Adamantane as a brain-directed drug carrier for poorly absorbed drug. 2.
       AZT derivatives conjugated with the 1-adamantane moiety.
 DT    9411
 AU    Tsuzuki N; Hama T; Kawada M; Hasui A; Konishi R; Shiwa S; Ochi Y; Futaki
       S; Kitagawa K; Telkoku Seiyaku Company Ltd., Kagawa, Japan.
 SO    J Pharm Sci. 1994 Apr;83(4):481-4. Unique Identifier : AIDSLINE
       MED/94322211
 AB    Five AZT (azidothymidine) prodrugs conjugated with the 1-adamantane
       moiety via an ester bond were synthesized to improve the transport of
       AZT into the central nervous system (CNS). In in vitro degradation
       studies with rat and human plasma, it was demonstrated that the prodrugs
       were degraded enzymatically and converted quantitatively to their parent
       drug. AZT. As assessed by octanol-buffer partitioning, the prodrugs were
       much more lipophilic than AZT and were expected to penetrate the
       blood-brain barrier (BBB) readily. In in vivo studies, in which the
       prodrugs were administered intravenously to rat, the prodrugs in brain
       tissue were detected at 7-18 times higher concentrations than AZT in
       spite of the negligible amount of the prodrug in the cerebrospinal
       fluid. These results indicate that the introduction to AZT of the
       1-adamantane moiety results in the enhancement of the BBB penetration.
       This pharmaceutical approach would be beneficial for the efficient
       treatment of the CNS infection by human immunodeficiency virus.
 DE    Adamantane/*PHARMACOLOGY/PHARMACOKINETICS  Animal  Blood-Brain
       Barrier/PHYSIOLOGY  Brain/*METABOLISM  Chemistry, Physical
       Chromatography, High Pressure Liquid  Drug Carriers  Human  Hydrolysis
       In Vitro  Male  Prodrugs/CHEMICAL
       SYNTHESIS/*PHARMACOLOGY/PHARMACOKINETICS  Rats  Rats, Wistar
       Zidovudine/ANALOGS & DERIVATIVES/ADMINISTRATION & DOSAGE/
       *PHARMACOKINETICS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).