Article

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

Dafra Pharma Research & Development, Slachthuislaan 30/7, B-2300 Turnhout, Belgium.
Journal of Antimicrobial Chemotherapy (Impact Factor: 5.44). 07/2012; 67(11):2707-12. DOI: 10.1093/jac/dks273
Source: PubMed

ABSTRACT 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 <5 μM, while the IC(50) values for Leishmania major and Leishmania braziliensis were 7.7 and 13.5 μM, respectively. These results are fairly similar to those obtained for miltefosine. In the hamster model, treatment with 20 and 40 mg/kg for 5 days proved that both OlPC formulations were equipotent and showed a markedly higher efficacy compared with miltefosine. A single dosing of 100 mg/kg of OlPC/H(2)O or OlPC liposomes reduced the parasite burdens by 96.2% and 99.3% in liver, 99.8% and 99.9% in spleen, and 87.6% and 96.9% in bone marrow, respectively. No signs of toxicity or adverse drug-related effects were noted.
These data suggest that OlPC may become a promising candidate to improve and simplify current case management of VL. Additional pharmacological and pharmacokinetic studies are ongoing to assess the full potential of OlPC as a 'drug candidate'.

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    • "The selected drug for this proof-of-concept project is oleylphosphocholine (OlPC), an alkylphosphocholine formulated as liposomes of about 100 nm which can be directly used for tattooing. In a previous study, the OlPC active pharmaceutical ingredient showed good in vitro activity against several CL-causing strains of Leishmania (L.), including L. major, L. tropica, L. mexicana, L. panamensis and L. braziliensis4. These data prompted us to study the in vivo efficacy of this drug against CL when formulated as liposomes and delivered with a tattoo instrument while comparing to other, more classical, administration routes. "
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