In vivo antileishmanial activity of hexadecylphosphocholine and other alkylphosphocholines

Hexadecylphosphocholine (HPC) and several other alkylphosphocholines were t ested against three strains of leishmania (Leishmania donovani MHOM/IN/54LR C-L.51; Leishmania donovani MHOM/IN80/DD8; and Leishmania infantum MHOM/ES8 6/STI-172). In in vitro studies HPC showed IC50 Values between 0.9 and 2 mu g/ml in all three strains. Octadecenylphosphocholine was the most active c ompound against the promastigote LRC-L.51 with an IC50 value of 0.41 mu g/m l. In in vivo studies in infected female Balb/c mice, HPC revealed the most pronounced antileishmanial activity among the orally applied formulations of alkylphosphocholines. With respect to the parasite burden in liver, the subcutaneous application of the reference compound pentostam (120 mg/kg/day ) was as effective when compared to orally applied HPC (20 mg/kg/day). Howe ver, at identical doses the treatment with HPC resulted in a more than 600- fold greater number of parasites in the spleen. Liposomal HPC was very well tolerated. At a drug concentration of 20 mg/kg/day (5 days a week for 3 we eks) parasites could not be detected by microscopy in liver smears. Compare d to pentostam the magnitude of parasite reduction in the spleen by liposom al HPC differed by a factor of more than 1,000 in favor of liposomal HPC. T reatment with liposomal HPC for 3 weeks at a dose of 30 mg/kg/day (5 days a week) cured about 50% of the infected mice. When taken together, alkylphos phocholines represent a powerful new group of compounds in the treatment of visceral leishmaniasis. Clinical trials in humans are therefore highly war ranted. (C) Prous Science. All rights reserved.