Document 0775
 DOCN  M9550775
 TI    Antiviral efficacy, intracellular uptake and pharmacokinetics of free
       and liposome-encapsulated 2',3'-dideoxyinosine.
 DT    9505
 AU    Desormeaux A; Harvie P; Perron S; Makabi-Panzu B; Beauchamp D; Tremblay
       M; Poulin L; Bergeron MG; Laboratoire et Service d'Infectiologie, Centre
       Hospitalier de; l'Universite Laval, Quebec, Canada.
 SO    AIDS. 1994 Nov;8(11):1545-53. Unique Identifier : AIDSLINE MED/95151231
 AB    OBJECTIVE: To evaluate the effect of liposome encapsulation on the in
       vitro antiviral efficacy, intracellular uptake and in vivo
       pharmacokinetics of 2',3'-dideoxyinosine (ddl). METHODS: The
       accumulation of free and liposome-encapsulated ddl was determined in
       murine monocyte-macrophage RAW 264.7 cells and human premonocytoid U937
       cells. The antiviral efficacy was evaluated in U937 cells infected with
       HIVIIIB. Tissue distribution and pharmacokinetics of free and liposomal
       ddl were determined in female Sprague-Dawley rats following the
       administration of a single intravenous bolus dose (3 mg ddl/kg).
       RESULTS: The entrapment of ddl in liposomes results in a lower drug
       accumulation in both U937 and RAW 264.7 cells. A lower antiviral
       efficacy against HIVIIIB replication in U937 cells was observed on
       encapsulation of ddl in liposomes. Improved pharmacokinetics were
       observed on entrapment of ddl in liposomes. Higher drug levels were
       found in plasma for the liposomal formulation. The systemic clearance of
       the liposomal drug was 120 times lower than that of free drug. Liposome
       encapsulation of ddl greatly enhanced the drug accumulation in organs of
       the reticuloendothelial system. CONCLUSION: The encapsulation of ddl in
       liposomes modified the tissue distribution and plasma pharmacokinetics
       of the antiviral agent resulting in a marked improvement of drug
       biodisponibility. The antiviral efficacy of liposomal ddl was lower than
       that of free drug in HIVIIIB-infected U937 cells.
 DE    Analysis of Variance  Animal  Biological Transport  Cell Line  Cell
       Survival/DRUG EFFECTS  Comparative Study  Didanosine/*ADMINISTRATION &
       DOSAGE/PHARMACOLOGY/PHARMACOKINETICS  Drug Carriers  Enzyme-Linked
       Immunosorbent Assay  Human  HIV/*DRUG EFFECTS/METABOLISM  HIV Core
       Protein p24/ANALYSIS  Kinetics  Liposomes  Lymphoma, Large-Cell
       Macrophages  Male  Mice  Monocytes  Phosphatidylcholines
       Phosphatidylglycerols  Rats  Rats, Sprague-Dawley  Support, Non-U.S.
       Gov't  Time Factors  1,2-Dipalmitoylphosphatidylcholine  JOURNAL ARTICLE

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