       Document 0673
 DOCN  M9620673
 TI    Lymphatic distribution of 3'-azido-3'-deoxythymidine and
       3'-azido-2',3'-dideoxyuridine in mice.
 DT    9602
 AU    Manouilov KK; White CA; Boudinot FD; Fedorov II; Chu CK; Department of
       Pharmaceutics, College of Pharmacy, University of; Georgia, Athens
       30602-2353, USA.
 SO    Drug Metab Dispos. 1995 Jun;23(6):655-8. Unique Identifier : AIDSLINE
       MED/96075725
 AB    Recently, it was shown that human immunodeficiency virus (HIV)-infected
       cells preferentially locate in lymphoid tissue early in the course of
       infection. Therefore, it is important to characterize the disposition of
       the anti-HIV agents, 3'-azido-3'-deoxythymidine (AZT) and 3'-azido-2',
       3'-dideoxyuridine (AZdU), in the lymphatic system. The disposition of
       AZT and AZdU in serum and neck, axillary, and mesenteric lymph nodes was
       studied in mice after intravenous, oral, and intraperitoneal
       administrations of 50 mg/kg doses. Samples were collected at 0.08, 0.5,
       1, 2, 3, 4, and 6 hr after dosing and nucleoside concentrations were
       determined by HPLC. Pharmacokinetic parameters were estimated using
       noncompartmental analysis. Maximum concentration, half-life, and area
       under the serum concentration vs. time curve (AUC) obtained from the
       serum concentration data were similar for both compounds after
       intravenous and intraperitoneal administrations; however, a difference
       in oral bioavailability for AZT and AZdU (49% and 76%, respectively) was
       noted. Patterns of regional distribution in lymph nodes were similar for
       both drugs; however, the accumulation of AZdU in the various lymph
       nodes, according to AUC values, was 3-76% greater than that for AZT. The
       relative exposure re = AUClymph/AUCserum) of both nucleosides exhibited
       a dependence on route of administration. Intravenous and oral
       administrations resulted in a greater distribution of nucleoside into
       axillary lymph nodes, compared with neck and mesenteric lymph nodes.
       Following intraperitoneal administration, however, distribution was
       similar in all three regions. AZT and AZdU distribute into the lymphatic
       system; however, AZdU accumulation was greater than that of
       AZT.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Animal  Antiviral Agents/BLOOD/*PHARMACOKINETICS  Female  Lymphoid
       Tissue/*METABOLISM  Mice  Support, U.S. Gov't, P.H.S.
       Zidovudine/*ANALOGS & DERIVATIVES/BLOOD/*PHARMACOKINETICS  JOURNAL
       ARTICLE

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

