Publication
Title
Efficacy and tolerability of oleylphosphocholine (OlPC) in a laboratory model of visceral leishmaniasis
Author
Abstract
Objectives 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. Methods The in vitro potency of OlPC was compared with that of miltefosine, amphotericin B, paromomycin and pentavalent antimony (SbV) 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 × 107 amastigotes (day 0) and oral treatment at day 21 using an aqueous (OlPC/H2O) 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). Results The in vitro activity of OlPC against Leishmania donovani, L. infantum, Leishmania tropica, Leishmania mexicana and Leishmania panamensis showed mean IC50 values <5 μM, while the IC50 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/H2O 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. Conclusions 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.
Language
English
Source (journal)
The journal of antimicrobial chemotherapy. - London, 1975, currens
Publication
London : 2012
ISSN
0305-7453 [print]
1460-2091 [online]
DOI
10.1093/JAC/DKS273
Volume/pages
67 :11 (2012) , p. 2707-2712
ISI
000309923800024
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 20.07.2012
Last edited 28.01.2024
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