Miltefosine

Structural formula
General
Non-proprietary name	Miltefosine
other names	Hexadecyl-2-trimethylazaniumylethylphosphate ( IUPAC )
Molecular formula	C 21 H 46 NO 4 P
External identifiers / databases
EC number	622-572-6
ECHA InfoCard	100.151.328
PubChem	3599
ChemSpider	3473
DrugBank	DB09031
Wikidata	Q411787
Drug information
ATC code	L01 XX09 , P01 CX04
Drug class	Antiprotozoal drugs , cytostatic drugs
properties
Molar mass	407.57 g · mol -1
Physical state	firmly
Melting point	232–234 ° C (decomposition)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 301-334
	P: 261-301 + 310-342 + 311
Toxicological data	246 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Miltefosine , a phospholipid from the alkyphosphocholine family with the substance name hexadecylphosphocholine , is a medicinal substance against the protozoa of leishmanias , the causative agents of leishmaniasis (kala-azar, dum-dum fever, aleppo bump or oriental bump). It has been shown to be effective against Leishmania donovani and Leishmania infantum in human and animal studies . The active ingredient is also used experimentally to treat infections with the amoeba Naegleria fowleri . Miltefosine is structurally related edelfosine and perifosine related.

Side effects

Orally administered miltefosine can cause mild to moderate gastrointestinal symptoms. A reversible increase in transaminases and creatinine can occur. Diarrhea and vomiting are relatively common, and skin irritation is not uncommon.

However, drug therapies alternative to miltefosine ( N -methylglucamine antimonate and amphotericin B ) are also known for their considerable side effects.

Development history

Miltefosine was developed in the 1990s at the Max Planck Institute for Biophysical Chemistry by Hansjörg Eibl and Clemens Unger and used as a therapeutic agent in the first clinical studies. Miltefosine has been approved for the treatment of leishmaniasis since 2004. The active ingredient is approved for animals in Spain, Italy, Greece and Switzerland.

Trade names

Monopreparations

Impavido (D, USA), Miltex (D, A)

Veterinary medicine: Milteforan (CH, I, E, GR)

literature

H. Sindermann, KR Engel u. a .: Oral miltefosine for leishmaniasis in immunocompromised patients: compassionate use in 39 patients with HIV infection. In: Clinical Infectious Diseases . Volume 39, number 10, November 2004, pp. 1520-1523, doi : 10.1086 / 425359 . PMID 15546090 .
S. Sundar, TK Jha et al. a .: Oral miltefosine for Indian visceral leishmaniasis. In: The New England journal of medicine . Volume 347, Number 22, November 2002, pp. 1739-1746, doi : 10.1056 / NEJMoa021556 . PMID 12456849 .
J. Soto, BA Arana et al. a .: Miltefosine for new world cutaneous leishmaniasis. In: Clinical Infectious Diseases . Volume 38, Number 9, May 2004, pp. 1266-1272, doi : 10.1086 / 383321 . PMID 15127339 .

Web links

"Deadly tropical disease now curable" - page of the Max Planck Institute for Biophysical Chemistry Göttingen on miltefosine
Sonja Klarhof: Oleyl phosphocholine, a new active ingredient for the treatment of canine visceral leishmaniasis , inaugural dissertation DNB 974396486/34
TK Jha, Shyam Sundar, CP Thakur, Peter Bachmann, Juntra Karbwang, Christina Fischer, Andreas Voss, Jonathan Berman: Miltefosine, an Oral Agent, for the Treatment of Indian Visceral Leishmaniasis. In: New England Journal of Medicine. 341, 1999, pp. 1795-1800, doi : 10.1056 / NEJM199912093412403 (free full text).
Center for Disease Control: Naegleria fowleri - Primary Amebic Meningoencephalitis (PAM) - Treatment

Individual evidence

↑ Entry on miltefosine. In: Römpp Online . Georg Thieme Verlag, accessed on June 1, 2014.
↑ ^a ^b Miltefosine data sheet from Sigma-Aldrich , accessed on April 10, 2011 ( PDF ).

↑ Miltefosine data sheet (PDF) from Calbiochem, accessed on December 8, 2015.

↑ Deadly tropical disease now curable. ( Memento of the original from March 4, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Max Planck Institute for Biophysical Chemistry Göttingen, press release from January 28, 2000. @1@ 2

↑ A. Kuhlencord, T. Maniera, H. Eibl, C. Unger: Hexadecylphosphocholine: oral treatment of visceral leishmaniasis in mice. In: Antimicrobial agents and chemotherapy . Volume 36, Number 8, August 1992, pp. 1630-1634, PMID 1329624 . PMC 192021 (free full text).

↑ IMPAVIDO- miltefosine capsule . DailyMed .

[1] Entry on miltefosine. In: Römpp Online . Georg Thieme Verlag, accessed on June 1, 2014.

[Sigma-2] Miltefosine data sheet from Sigma-Aldrich , accessed on April 10, 2011 ( PDF ).

[Calbiochem-3] Miltefosine data sheet (PDF) from Calbiochem, accessed on December 8, 2015.

[4] Deadly tropical disease now curable. ( Memento of the original from March 4, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Max Planck Institute for Biophysical Chemistry Göttingen, press release from January 28, 2000. @1@ 2

[PMID1329624-5] A. Kuhlencord, T. Maniera, H. Eibl, C. Unger: Hexadecylphosphocholine: oral treatment of visceral leishmaniasis in mice. In: Antimicrobial agents and chemotherapy . Volume 36, Number 8, August 1992, pp. 1630-1634, PMID 1329624 . PMC 192021 (free full text).

[label-6] IMPAVIDO- miltefosine capsule . DailyMed .