Document 1132
 DOCN  M94A1132
 TI    Intracellular phosphorylation of zidovudine in vivo.
 DT    9412
 AU    Veal GJ; Wild MJ; Barry MG; Back DJ; Dept of Pharmacology and
       Therapeutics, University of Liverpool,; England.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):201 (abstract no. PB0818). Unique
       Identifier : AIDSLINE ICA10/94371443
 AB    The anti-retroviral agent zidovudine (ZDV) is a prodrug requiring
       phosphorylation via various intracellular kinases to its active
       triphosphate form. We have investigated the intracellular metabolism of
       ZDV in vivo in human peripheral blood mononuclear cells (PBMCs) obtained
       from healthy volunteers (n = 5) and HIV +ve patients (n = 8) currently
       receiving ZDV therapy. Data obtained from such studies should provide a
       better marker for clinical efficacy than plasma concentration of the
       parent compound. PBMCs were isolated from blood by density cushion
       centrifugation at 0,1,2,4 and 6h post 250mg oral ZDV. Cells were washed
       and extracted overnight with 60% methanol prior to analysis by HPLC.
       Fractions eluted from the column corresponding to ZDV and its mono-, di-
       and triphosphate were collected and hydrolysed by acid phosphatase.
       Samples were cleaned up using Sep-Pak cartridges and ZDV levels
       quantified using a commercially available RIA (Sigma). TABULAR DATA, SEE
       ABSTRACT VOLUME. There was a marked difference in the extent of
       phosphorylation observed between patients and healthy volunteers. (Data
       expressed as mean +/- standard deviation with range of values in
       brackets).
 DE    Centrifugation, Density Gradient  Human  HIV Seropositivity/DRUG
       THERAPY/METABOLISM  Leukocytes, Mononuclear/*METABOLISM
       Phosphates/METABOLISM  Phosphorylation  Zidovudine/*METABOLISM  MEETING
       ABSTRACT

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