Long term improvement in the treatment of canine leishmaniosis using an antimony liposomal formulation

Pharmacokinetic and clinical effectiveness of liposome-encapsulated N-methy lglucamine antimoniate (LMA) was performed in dogs suffering from experimen tal leishmaniosis, LMA was compared with N-methylglucamine antimoniate (MGA ), the same drug in its free form. Sb plasma concentrations for LMA were al ways higher than those for MGA, Mean residence time (MRT), half-life time ( tau (1/2)) and clearance (Cl) showed that Sb was eliminated slower after Li posome administration. The high volume of distribution (Vd) obtained with L MA suggests that Sb could achieve therapeutic concentrations in parasite-in fected tissues. Average plasma concentration at steady state (Css(ave)) sho ws that Sb body concentrations after LMA treatment (9.8 mg/kg Sb, each 24 h ) 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 p rotein and gammaglobulin concentrations were within normal range, while for MGA both began to rise 3 months after treatment. Use of antimonial liposom al formulations may restore effectiveness to an existing drug and reduce to xicity. (C) 2001 Elsevier Science B.V. All rights reserved.