Document 1129
 DOCN  M94A1129
 TI    Disposition of AZT and AZdU in lymph nodes of mice.
 DT    9412
 AU    Chu CK; Manouilov KK; White CA; Federov I; Boudinot FD; Univ. of
       Georgia, Athens 30602.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):202 (abstract no. PB0822). Unique
       Identifier : AIDSLINE ICA10/94371446
 AB    OBJECTIVE: It has been shown that HIV-infected cells preferentially
       locate in lymphoid tissue in the early course of infection. Therefore,
       it is important to determine the disposition of anti-HIV agents, AZT and
       AZdU in the lymphatic system. METHODS: The pharmacokinetics of AZT and
       AZdU in lymph nodes have been studied in uninfected female mice after
       administration of 50 mg/kg doses via oral gavage, iv or ip injection.
       Serum and neck, axillary and mesenteric lymph nodes were collected at
       .08, 0.5, 1, 2, 3, and 4 hour. HPLC was used to quantitate AZT and AZdU.
       Pharmacokinetics parameters were estimated with the assistance of
       LAGRAN. The data were averaged for each time point. RESULTS: Cmax, t1/2,
       and AUC obtained from the plasma data were similar for both compounds
       with iv and ip administration; however, a difference in oral
       bioavailability for AZT and AZdU (49% and 75%, respectively) was noted.
       The accumulation of AZdU in lymph nodes, according to the AUC values,
       was 3-76% greater than AZT. Patterns of regional distribution in lymph
       nodes were similar for both drugs. However, AZdU produced greater
       accumulation. The relative exposure (re = AUCLN/AUCserum) of both drugs
       exhibited a dependence on route of administration. DISCUSSION AND
       CONCLUSIONS: The results suggest that AZdU has some pharmacokinetic
       advantages in lymphatic tissue and may be more useful for the treatment
       of the early stages of HIV infection than AZT.
 DE    Animal  Antiviral Agents/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS
       Female  Lymph Nodes/*METABOLISM  Mice  Support, U.S. Gov't, P.H.S.
       Zidovudine/*ANALOGS & DERIVATIVES/ADMINISTRATION & DOSAGE/
       *PHARMACOKINETICS  MEETING ABSTRACT

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