Efficacy and tolerability of oleylphosphocholine (OIPC) in a laboratory model of visceral leishmaniasis

The alkylphospholipid oleylphosphocholine (OlPC) is a structural analogue of miltefosine and may represent a potential therapeutic backup for the treatment of visceral leishmaniasis (VL). This laboratory study compared the in vitro and in vivo activity profile of both OlPC and miltefosine. The in vitro potency of OlPC was compared with that of miltefosine, amphotericin B, paromomycin and pentavalent antimony (Sb(V)) using the intracellular amastigote assay on different Old World and New World Leishmania species. The in vivo efficacy was dose titrated in the Leishmania infantum hamster model after infection with 2 × 10(7) amastigotes (day 0) and oral treatment at day 21 using an aqueous (OlPC/H(2)O) and liposomal formulation of OlPC in single and repeated (5 day) oral dosing regimens. The amastigote reductions in the liver, spleen and bone marrow were assessed (day 35). The in vitro activity of OlPC against Leishmania donovani, L. infantum, Leishmania tropica, Leishmania mexicana and Leishmania panamensis showed mean IC(50) values