Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis

• Published in: Journal of antimicrobial chemotherapy Vol. 67; no. 11; pp. 2576 - 2597
• Main Authors: Dorlo, T. P. C., Balasegaram, M., Beijnen, J. H., de Vries, P. J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2012; Oxford Publishing Limited (England)
• Subjects: Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiprotozoal Agents - adverse effects; Antiprotozoal Agents - pharmacokinetics; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - therapeutic use; Biological and medical sciences; Cancer; Cells; Clinical trials; Clinical Trials as Topic; Human protozoal diseases; Humans; Infectious diseases; Leishmania; Leishmania - drug effects; Leishmaniasis - drug therapy; Leshmaniasis; Medical sciences; Parasites; Parasitic diseases; Pharmacology. Drug treatments; Phosphorylcholine - adverse effects; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - pharmacokinetics; Phosphorylcholine - pharmacology; Phosphorylcholine - therapeutic use; Protozoal diseases; Side effects; Treatment Outcome; East Africa; South Asia; Asia; Africa; India; Antineoplastic agent; Skin disease; Protozoal disease; antiprotozoal agents; Phospholipid; Kala azar; Review; Cutaneous leishmaniasis; Antiprotozoal agent; alkylphosphocholine; Mechanism of action; Kinetoplastida; Protozoa; Pharmacodynamics; antiparasitic agents; Treatment efficiency; Leishmaniasis; Parasitosis; Biological activity; Infection; Miltefosine; Treatment; Leishmania; Lysophospholipid; Clinical pharmacology; Parasiticide; pre-clinical pharmacology; Pharmacokinetics; visceral leishmaniasis; Bibliographic review
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dks275

Miltefosine is an alkylphosphocholine drug with demonstrated activity against various parasite species and cancer cells as well as some pathogenic bacteria and fungi. For 10 years it has been licensed in India for the treatment of visceral leishmaniasis (VL), a fatal neglected parasitic disease. It is the first and still the only oral drug that can be used to treat VL and cutaneous leishmaniasis (CL). The standard 28 day miltefosine monotherapy regimen is well tolerated, except for mild gastrointestinal side effects, although its teratogenic potential severely hampers its general use in the clinic and roll-out in national elimination programmes. The pharmacokinetics of miltefosine are mainly characterized by its long residence time in the body, resulting in extensive drug accumulation during treatment and long elimination half-lives. At the moment, different combination therapy strategies encompassing miltefosine are being tested in multiple controlled clinical trials in various geographical areas of endemicity, both in South Asia and East Africa. We here review the most salient pre-clinical and clinical pharmacological aspects of miltefosine, its mechanism of action against Leishmania parasites and other pathogens, and provide a systematic overview of the efficacy and safety data from all clinical trials of miltefosine, either alone or in combination, in the treatment of VL and CL.