       Document 0124
 DOCN  M94A0124
 TI    Activity of liposomal amphotericin B (AmBisome) against Leishmania
       infantum and tissue distribution in mice.
 DT    9412
 AU    Gradoni L; Davidson RN; Orsini S; Betto P; Giambenedetti M; Laboratorio
       di Parassitologia, Istituto Superiore di Sanita,; Rome, Italy.
 SO    J Drug Target. 1993;1(4):311-6. Unique Identifier : AIDSLINE
       MED/94348809
 AB    Preliminary observations have shown that AmBisome, a liposomal
       formulation of amphotericin B (Vestar Inc.), is effective and non-toxic
       in animal and human visceral leishmaniasis. The activity of multiple
       doses of this drug on Leishmania infantum, in BALB/c mice was
       investigated, and amphotericin B concentration in liver and spleen was
       determined. Groups of infected mice were treated intravenously with 3,
       5, or 7 doses of AmBisome (3 mg/kg) over 3, 10 and 25 days,
       respectively. The antileishmanial activity of the drug was compared with
       that of meglumine antimoniate (28 mg Sbv/kg per day over 21 days). Three
       consecutive daily doses of AmBisome were sufficient to clear all
       parasites from the liver of mice, while antimony did so only after 21
       doses. Twenty-four-48 h after their last dose all the AmBisome-treated
       mice showed very high amphotericin B concentrations in liver (61.2-76.2
       micrograms/g) and spleen (39.8-72.1 micrograms/g) with no overt signs of
       toxicity. Mice that received 2 or 4 doses at intervals of 5 to 8 days,
       maintained drug levels as high as those detected after 3 consecutive
       doses over 11 and 26 days, respectively. This should enable visceral
       leishmaniasis treatment on an intermittent or outpatient basis, thereby
       reducing overall treatment costs.
 DE    Amphotericin B/PHARMACOKINETICS/TOXICITY/*THERAPEUTIC USE  Animal
       Hamsters  Human  HIV Infections/COMPLICATIONS  Infant, Newborn
       *Leishmania infantum  Leishmaniasis, Visceral/COMPLICATIONS/*DRUG
       THERAPY/PARASITOLOGY  Liposomes  Liver/METABOLISM  Meglumine/THERAPEUTIC
       USE  Mice  Mice, Inbred BALB C  Organometallic Compounds/THERAPEUTIC USE
       Spleen/METABOLISM  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).

