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Miltefosine
Systematic (IUPAC) name
2-(hexadecoxy-oxido-phosphoryl)oxyethyl-trimethyl-azanium
Identifiers
CAS number 58066-85-6
ATC code L01XX09
PubChem 3599
Chemical data
Formula C21H46NO4P 
Mol. mass 407.568 g/mol
Pharmacokinetic data
Bioavailability High
Half life 6 to 8 days and 31 days [1]
Therapeutic considerations
Pregnancy cat.  ?
Legal status
Routes Oral

Miltefosine (INN, trade names Impavido and Miltex) is an antiprotozoal drug. Originally developed as an antineoplastic, it is finding use as an antiprotozoal drug. It can be administered orally and topically.

It is also under investigation as a potential therapy against HIV infection.[2][3]

Contents

Current antiprotozoal and antifungal applications

Leishmania: Miltefosine is registered and used by Zentaris GmbH in India, Colombia and Germany for the treatment of visceral and cutaneous leishmaniasis, and is undergoing clinical trials for this use in several other countries, such as Brazil[4] and Guatemala.[5] It is currently the only effective oral treatment for leishmaniasis.

Miltefosine is one of the few orally administered drugs that is effective against Leishmania. [6]

Investigatory antiprotozoal and antifungal usage

Miltefosine is being investigated by researchers interested in finding treatments for infections which have become resistant to existing drugs. Animal and in-vitro studies suggest it may have broad anti-protozoal and anti-fungal properties:

  • An in-vitro study found that Miltefosine is effective against metronidazole-resistant variants of Trichomonas vaginalis, a sexually transmitted protozoal disease.[9]

Investigatory usage against HIV infection

Miltefosine targets HIV infected macrophages, which play a role in vivo as long-lived HIV-1 reservoirs. The HIV protein Tat activates pro-survival PI3K/Akt pathway in primary human macrophages. Miltefosine acts by inhibiting the PI3K/Akt pathway, thus removing the infected macrophages from circulation, without affecting healthy cells.[3]

Side effects

The main side effects reported with miltefosine treatment are nausea and vomiting. Miltefosine has exhibited teratogenicity, and should not be administered to pregnant women.

References

  1. ^ Dorlo TP, van Thiel PP, Huitema AD, Keizer RJ, de Vries HJ, Beijnen JH, de Vries PJ (2008). "Pharmacokinetics of miltefosine in Old World cutaneous leishmaniasis patients.". Antimicrob Agents Chemother 52 (8): 2855–60. doi:10.1128/AAC.00014-08. PMID 18519729. 
  2. ^ "Parasitic Drug Shows HIV-Fighting Promise". AIDSmeds.com. 2008-02-01. http://www.aidsmeds.com/articles/hiv_miltefosine_macrophages_1667_13933.shtml. Retrieved 2008-02-02. 
  3. ^ a b Chugh P, Bradel-Tretheway B, Monteiro-Filho CM, et al. (2008). "Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy". Retrovirology 5 (1): 11. doi:10.1186/1742-4690-5-11. PMID 18237430. 
  4. ^ Cristina, Márcia; Pedrosa, Robert (September 2005). "Hospital de Doenças Tropicais testa droga contra calazar" (in Portuguese). Sapiência (Fundação de Amparo à Pesquisa do Estado do Piauí). http://www.fapepi.pi.gov.br/sapiencia6/pesquisa3.php. Retrieved 2006-09-01. 
  5. ^ Soto J, Berman J (2006). "Treatment of New World cutaneous leishmaniasis with miltefosine.". Trans R Soc Trop Med Hyg 100: S34. doi:10.1016/j.trstmh.2006.02.022. PMID 16930649. 
  6. ^ Berman J (2005). "Clinical status of agents being developed for leishmaniasis". Expert opinion on investigational drugs 14 (11): 1337–46. doi:10.1517/13543784.14.11.1337. PMID 16255674. 
  7. ^ Saraiva V, Gibaldi D, Previato J, Mendonça-Previato L, Bozza M, Freire-De-Lima C, Heise N (2002). "Proinflammatory and cytotoxic effects of hexadecylphosphocholine (miltefosine) against drug-resistant strains of Trypanosoma cruzi.". Antimicrob Agents Chemother 46 (11): 3472–7. doi:10.1128/AAC.46.11.3472-3477.2002. PMID 12384352. 
  8. ^ Widmer F, Wright L, Obando D, Handke R, Ganendren R, Ellis D, Sorrell T (2006). "Hexadecylphosphocholine (miltefosine) has broad-spectrum fungicidal activity and is efficacious in a mouse model of cryptococcosis.". Antimicrob Agents Chemother 50 (2): 414–21. doi:10.1128/AAC.50.2.414-421.2006. PMID 16436691. 
  9. ^ Blaha C, Duchêne M, Aspöck H, Walochnik J (2006). "In vitro activity of hexadecylphosphocholine (miltefosine) against metronidazole-resistant and -susceptible strains of Trichomonas vaginalis". J. Antimicrob. Chemother. 57 (2): 273–8. doi:10.1093/jac/dki417. PMID 16344287. 
  10. ^ Choubey V, Maity P, Guha M, et al. (February 2007). "Inhibition of Plasmodium falciparum choline kinase by hexadecyltrimethylammonium bromide: a possible antimalarial mechanism". Antimicrob. Agents Chemother. 51 (2): 696–706. doi:10.1128/AAC.00919-06. PMID 17145794. 
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