Pharmacokinetics and pharmacodynamics of oleylphosphocholine in a hamster model of visceral leishmaniasis

J Antimicrob Chemother. 2016 Jul;71(7):1892-8. doi: 10.1093/jac/dkw089. Epub 2016 Apr 15.


Objectives: This study evaluated the pharmacokinetic properties of oleylphosphocholine (OlPC) in hamsters following a single oral dose. Its prophylactic activity was tested to establish exposure-activity relationships, while a 5 + 5 day oral regimen at 20 mg/kg with long post-treatment follow-up was performed to assess its curative potential.

Methods: Single oral doses of 20, 50 and 100 mg/kg were administered for pharmacokinetic analysis while a 100 mg/kg single oral dose was given on day 7, 4 or 1, or 4 h prior to infection in the prophylactic efficacy study. The animals were infected on day 0 with Leishmania infantum and the resulting parasite burdens were measured in target organs on day 21. In the curative model, treatment started on day 21 post-infection at 20 mg/kg for 5 + 5 days and amastigote burdens were determined in target organs either on day 42 [10 days after the end of treatment (dpt)] or day 72 (40 dpt).

Results: OlPC showed elimination t1/2 of ∼50 h and dose-proportional exposure. The prophylactic action of OlPC was in agreement with model-simulated drug exposures, showing dose-dependent residual activity. Interestingly, the 100 mg/kg single dose administered 4 days before infection (day -4) still reduced the overall parasite burden by ∼50%. In the curative model, >99% clearance of infection was observed at 10 dpt in all OlPC-treated animals and remained so at 40 dpt.

Conclusions: This study reveals that total plasma exposure (AUCt-∞) correlates well with the prophylactic and curative efficacy of OlPC in the L. infantum hamster model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antiprotozoal Agents / administration & dosage
  • Antiprotozoal Agents / pharmacokinetics*
  • Antiprotozoal Agents / pharmacology*
  • Area Under Curve
  • Chemoprevention / methods
  • Disease Models, Animal
  • Female
  • Leishmania infantum / drug effects*
  • Leishmaniasis, Visceral / drug therapy*
  • Leishmaniasis, Visceral / prevention & control*
  • Mesocricetus
  • Phosphorylcholine / administration & dosage
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / pharmacokinetics
  • Phosphorylcholine / pharmacology
  • Plasma / chemistry


  • Antiprotozoal Agents
  • oleylphosphocholine
  • Phosphorylcholine