Development of miltefosine as an oral treatment for leishmaniasis

Trans R Soc Trop Med Hyg. 2006 Dec:100 Suppl 1:S17-20. doi: 10.1016/j.trstmh.2006.02.010. Epub 2006 May 26.

Abstract

Miltefosine was originally formulated and registered as a topical treatment for cutaneous cancers. For this indication and in subsequent development for leishmaniasis, a large body of non-clinical data has been generated. The gastrointestinal organ is the main site of toxicity, in both animal and in human studies. The testis and retina were identified as target organs in rats, although corresponding changes were not observed in clinical studies in humans. In terms of pharmacokinetics, the terminal elimination half-life is long (84h and 159h in rats and dogs respectively). Miltefosine is widely distributed in body organs and not metabolized by cytochrome P450 enzymes in vitro. The drug is embryotoxic and fetotoxic in rats and rabbits, and teratogenic in rats but not in rabbits. It is therefore contraindicated for use during pregnancy, and contraception is required beyond the end of treatment in women of child-bearing age.

Publication types

  • Review

MeSH terms

  • Abnormalities, Drug-Induced / etiology
  • Administration, Oral
  • Animals
  • Antineoplastic Agents / toxicity
  • Antiprotozoal Agents / administration & dosage*
  • Antiprotozoal Agents / pharmacokinetics
  • Antiprotozoal Agents / toxicity
  • Chemical and Drug Induced Liver Injury
  • Disease Models, Animal
  • Dogs
  • Drug Evaluation
  • Eye Diseases / chemically induced
  • Female
  • Hematologic Diseases / chemically induced
  • Humans
  • Kidney Diseases / chemically induced
  • Leishmaniasis / drug therapy*
  • Phosphorylcholine / administration & dosage
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / pharmacokinetics
  • Phosphorylcholine / toxicity
  • Pregnancy
  • Rats
  • Teratogens / toxicity

Substances

  • Antineoplastic Agents
  • Antiprotozoal Agents
  • Teratogens
  • Phosphorylcholine
  • miltefosine