Long term improvement in the treatment of canine leishmaniosis using an antimony liposomal formulation.
Pharmacokinetic and clinical effectiveness of liposome-encapsulated N-methylglucamine antimoniate (LMA) was performed in dogs suffering from experimental leishmaniosis. LMA was compared with N-methylglucamine antimoniate (MGA), the same drug in its free form. Sb plasma concentrations for LMA were always higher than those for MGA. Mean residence time (MRT), half-life time (t(1/2)) and clearance (Cl) showed that Sb was eliminated slower after liposome administration. The high volume of distribution (Vd) obtained with LMA suggests that Sb could achieve therapeutic concentrations in parasite-infected tissues. Average plasma concentration at steady state (Css(ave)) shows that Sb body concentrations after LMA treatment (9.8 mg/kg Sb, each 24h) would be effective in Leishmania infantum canine infection. Comparing LMA with MGA in a 1-year follow-up we observed no relapses for LMA and total protein and gammaglobulin concentrations were within normal range, while for MGA both began to rise 3 months after treatment. Use of antimonial liposomal formulations may restore effectiveness to an existing drug and reduce toxicity.
Valladares
J E
JE
Departament de Farmacologia i Terapèutica, Facultat de Veterinària, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Barcelona, Spain.
Riera
C
C
González-Ensenyat
P
P
Díez-Cascón
A
A
Ramos
G
G
Solano-Gallego
L
L
Gállego
M
M
Portús
M
M
Arboix
M
M
Alberola
J
J
D000818:Animals; D000965:Antimony / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D007896:Leishmaniasis / Q000188:drug therapy / Q000662:veterinary*; D008081:Liposomes; D008297:Male
D003692:Delayed-Action Preparations; D008081:Liposomes; D000965:Antimony