Miltefosine
From Wikipedia, the free encyclopedia
 |
|
|
Miltefosine
|
|
| Systematic (IUPAC) name | |
| 2-(hexadecoxy-oxido-phosphoryl)oxyethyl-trimethyl-azanium | |
| Identifiers | |
| CAS number | |
| ATC code | L01 |
| PubChem | |
| Chemical data | |
| Formula | C21H46NO4P |
| Mol. mass | 407.568 g/mol |
| Pharmacokinetic data | |
| Bioavailability | High |
| Metabolism | ? |
| Half life | 6 to 8 days |
| Excretion | ? |
| 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 intravenously.
It is also under investigation as a potential therapy against HIV infection.[1][2]
Contents |
[edit] 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[3] and Guatemala.[4] It is currently the only effective oral treatment for leishmaniasis.
Miltefosine is one of the few orally administered drugs that is effective against Leishmania [5]
[edit] 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:
- Animal studies suggest miltefosine may also be effective against Trypanosoma cruzi, the parasite responsible for Chagas' disease. [6]
- Several studies have found the drug to be effective against Cryptococcus neoformans, Candida, Aspergillus and Fusarium.[7]
- An in-vitro study found that Miltefosine is effective against metronidazole-resistant variants of Trichomonas vaginalis, a sexually transmitted protozoal disease.[8]
- Hexadecyltrimethylammonium bromide, a compound structurally similar to miltefosine, was recently found to exhibit potent in vitro activity against Plasmodium falciparum.[9]
[edit] 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.[2]
[edit] 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.
[edit] References
- ^ Parasitic Drug Shows HIV-Fighting Promise. AIDSmeds.com (2008-2-1). Retrieved on 2008-02-02.
- ^ 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:. PMID 18237430.
- ^ Cristina, Márcia; Pedrosa, Robert. "Hospital de Doenças Tropicais testa droga contra calazar", Sapiência, Fundação de Amparo à Pesquisa do Estado do Piauí, September 2005. Retrieved on 2006-09-01. (Portuguese)
- ^ Soto J, Berman J (2006). "Treatment of New World cutaneous leishmaniasis with miltefosine.". Trans R Soc Trop Med Hyg 100: S34. doi:. PMID 16930649.
- ^ Berman J (2005). "Clinical status of agents being developed for leishmaniasis". Expert opinion on investigational drugs 14 (11): 1337–46. doi:. PMID 16255674.
- ^ 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:. PMID 12384352.
- ^ 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:. PMID 16436691.
- ^ 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:. PMID 16344287.
- ^ Choubey V, Maity P, Guha M, Kumar S, Shrivastava K, Puri SK, Bandyopadhyay U (2006). "Inhibition of Plasmodium falciparum choline kinase by hexadecyltrimethylammonium bromide: A possible antimalarial mechanism of hexadecyltrimethylammonium bromide.". Antimicrob Agents Chemother. doi:. PMID 17145794.
|
|||||||||||||||||||||||||||||
|
|||||||||||||||||
