       Document 1074
 DOCN  M9621074
 TI    Encapsulation of foscarnet in liposomes modifies drug intracellular
       accumulation, in vitro anti-HIV-1 activity, tissue distribution and
       pharmacokinetics.
 DT    9602
 AU    Dusserre N; Lessard C; Paquette N; Perron S; Poulin L; Tremblay M;
       Beauchamp D; Desormeaux A; Bergeron MG; Centre de Recherche en
       Infectiologie, Centre Hospitalier de; I'Universite Laval, Ste-Foy,
       Quebec, Canada.
 SO    AIDS. 1995 Aug;9(8):833-41. Unique Identifier : AIDSLINE MED/96014955
 AB    OBJECTIVE: To improve the in vitro anti-HIV-1 activity, intracellular
       accumulation in macrophages and in vivo pharmacokinetics and tissue
       distribution of foscarnet (trisodium phosphonoformate; PFA) by
       encapsulation in liposomes. METHODS: The accumulation of free and
       liposome-encapsulated PFA was determined in monocyte-macrophage RAW
       264.7 cells and human premonocytoid U937 cells. The antiviral activity
       was evaluated in U937 cells infected with HIV-1IIIB. Tissue distribution
       and pharmacokinetics of free and liposomal PFA were determined in female
       Sprague-Dawley rats following the administration of an intravenous bolus
       dose (10 mg PFA/kg). RESULTS: The entrapment of PFA in liposomes
       resulted in a higher drug accumulation in both U937 and RAW 264.7 cells.
       A slightly greater efficacy against HIV-1IIIB replication into U937
       cells was observed upon encapsulation of PFA into liposomes. Improved
       pharmacokinetics was observed upon entrapment of PFA in liposomes. Much
       higher drug levels were found in plasma for the liposomal formulation.
       The systemic clearance of the liposomal drug was 77 times lower than
       that of free drug. The encapsulation of PFA in liposomes greatly
       enhanced the drug accumulation in organs of the reticuloendothelial
       system. CONCLUSION: The encapsulation of PFA in liposomes modified the
       tissue distribution and plasma pharmacokinetics of the antiviral agent,
       resulting in a marked improvement of drug accumulation in organs
       involved in HIV immunopathogenesis and in a greater PFA bioavailability.
       The antiviral activity of liposomal PFA was slightly greater than that
       of free drug in HIV-1IIIB-infected U937 cells.
 DE    Animal  Antiviral Agents/*ADMINISTRATION & DOSAGE/PHARMACOLOGY/
       *PHARMACOKINETICS  Base Sequence  Cell Line  DNA Primers/GENETICS  DNA,
       Viral/GENETICS  Female  Foscarnet/*ADMINISTRATION &
       DOSAGE/PHARMACOLOGY/*PHARMACOKINETICS  Human  HIV-1/*DRUG
       EFFECTS/GENETICS  Injections, Intravenous  Liposomes
       Macrophages/METABOLISM  Molecular Sequence Data  Polymerase Chain
       Reaction  Rats  Rats, Sprague-Dawley  Support, Non-U.S. Gov't  Tissue
       Distribution  JOURNAL ARTICLE

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

