Miltefosine

Last updated
Miltefosine
Miltefosine structure.svg
Miltefosine-3D-bs-17.png
Clinical data
Trade names Impavido, Miltex, others
AHFS/Drugs.com Monograph
License data
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances) [1]
  • US: WARNING [2] Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability High
Protein binding ~98%
Metabolism Slow hepatic (non-CYP-dependent)
Elimination half-life 6 to 8 days and 31 days [3]
Excretion Primarily fecal
Identifiers
  • 2-(hexadecoxy-oxido-phosphoryl)oxyethyl-trimethyl-azanium
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard 100.151.328 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H46NO4P
Molar mass 407.576 g·mol−1
3D model (JSmol)
Melting point 232 to 234 °C (450 to 453 °F)
  • [O-]P(=O)(OCCCCCCCCCCCCCCCC)OCC[N+](C)(C)C
  • InChI=1S/C21H46NO4P/c1-5-6-7-8-9-10-11-12-13-14-15-16-17-18-20-25-27(23,24)26-21-19-22(2,3)4/h5-21H2,1-4H3 Yes check.svgY
  • Key:PQLXHQMOHUQAKB-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as Naegleria fowleri and Balamuthia mandrillaris . [4] This includes the three forms of leishmaniasis: cutaneous, visceral and mucosal. [5] It may be used with liposomal amphotericin B or paromomycin. [6] It is taken by mouth. [5]

Contents

Common side effects include vomiting, abdominal pain, fever, headaches, and decreased kidney function. [4] More severe side effects may include Stevens–Johnson syndrome or low blood platelets. [4] Use during pregnancy appears to cause harm to the baby and use during breastfeeding is not recommended. [4] How it works is not entirely clear. [4]

Miltefosine was first made in the early 1980s and studied as a treatment for cancer. [7] A few years later it was found to be useful for leishmaniasis and was approved for this use in 2002 in India. [8] It is on the World Health Organization's List of Essential Medicines. [9] [10]

Medical uses

Leishmaniasis

Miltefosine is primarily used for the treatment of visceral and New World cutaneous leishmaniasis, and is undergoing clinical trials for this use in several countries. [11] [12] This drug is now listed as a core medication for the treatment of leishmaniasis under the WHO Model List of Essential Medicines. [13] Several medical agents have some efficacy against visceral or cutaneous leishmaniasis, however, a 2005 survey concluded that miltefosine is the only effective oral treatment for both forms of leishmaniasis. [14]

Amoeba infections

Miltefosine has been used successfully in some cases of the very rare, but highly lethal, brain infection by the amoeba, Naegleria fowleri , acquired through water entering the nose during a plunge in contaminated water. [15] It has orphan drug status in the United States for acanthamoeba keratitis and primary amebic meningoencephalitis (PAM). [16] [17]

Pregnancy and breastfeeding

Miltefosine is listed as pregnancy category D by the FDA. This means there is evidence-based adverse reaction data from investigational or marketing experience or studies in humans of harm to the human fetus. [18] Despite this evidence, the potential benefits of miltefosine may warrant use of the drug in pregnant women despite potential risks. A pregnancy test should be done prior to starting treatment. Effective birth control should be used while on miltefosine and 5 months after discontinuation of treatment. Its use during breast feeding is most likely unsafe. [3]

Contraindications

Miltefosine is contraindicated in individuals who have a hypersensitivity to this medication, pregnant women, and people who have the Sjögren-Larsson syndrome. [19] It 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. [20]

Side effects

Common side effects from miltefosine treatment are nausea and vomiting, which occur in 60% of people. Other common side effects are dizziness, headache, and daytime sleepiness. [21]

Serious side effects include rash, diarrhea, and arthritis. [21] The side effects are more severe in women and young children. The overall effects are quite mild and easily reversed. [22]

Mechanism of action

Miltefosine primarily acts on Leishmania by affecting the species's promastigote and amastigote stages. [23] Miltefosine exerts its activity by interacting with lipids, inhibiting cytochrome c oxidase and causing apoptosis-like cell death. [24] This may affect membrane integrity and mitochondrial function of the parasite.[ citation needed ]

History

Cancer

While initially studied as a cancer medication, due to side effects it was never used for this purpose. [25]

Phospholipid group alkylphosphocholine were known since the early 1980s, particularly in terms of their binding affinity with cobra venom. [26] In 1987 the phospholipids were found to be potent toxins on leukemic cell culture. [27] Initial in vivo investigation on the antineoplastic activity showed positive result, but then only at high dosage and at high toxicity. [28] At the same time in Germany, Hansjörg Eibl, at the Max Planck Institute for Biophysical Chemistry, and Clemens Unger, at the University of Göttingen, demonstrated that the antineoplastic activity of the phospholipid analogue miltefosine (at the time known as hexadecylphosphocholine) was indeed tumour-specific. It was highly effective against methylnitrosourea-induced mammary carcinoma, but less so on transplantable mammary carcinomas and autochthonous benzo(a)pyrene-induced sarcomas, and relatively inactive on Walker 256 carcinosarcoma and autochthonous acetoxymethylmethylnitrosamine-induced colonic tumors of rats. [29] [30] It was subsequently found that miltefosine was structurally unique among lipids having anticancer property in that it lacks the glycerol group, is highly selective on cell types and acts through different mechanism. [31] [32]

Leishmaniasis

In the same year as the discovery of the anticancer property, miltefosine was reported by S. L. Croft and his team at the London School of Hygiene and Tropical Medicine as having antileishmanial effect as well. The compound was effective against Leishmania donovani amastigotes in cultured mouse peritoneal macrophages at a dose of 12.8 mg/kg/day in a five-day course. [33] However, priority was given to the development of the compound for cutaneous metastases of breast cancer. In 1992 a new research was reported in which the compound was highly effective in mouse against different life cycle stages of different Leishmania species, and in fact, more potent than the conventional sodium stibogluconate therapy by a factor of more than 600. [34] Results of the first clinical trial in humans were reported from Indian patients with chronic leishmaniasis with high degree of success and safety. [35] This promising development promulgated a unique public–private partnership collaboration between ASTA Medica (later Zentaris GmbH), the World Health Organization (WHO) Special Programme for Research and Training in Tropical Diseases, and the Government of India. Eventually, several successful Phase II and III trials led to the approval of miltefosine in 2002 as the first and only oral drug for leishmaniasis. [3]

Naegleria fowleri and Acanthamoeba

In 2013, the US Centers for Disease Control and Prevention recommended miltefosine for the treatment of free-living amoeba infections such as granulomatous amoebic encephalitis and primary amoebic meningoencephalitis, two fatal protozoal diseases. [36] Historically, only four survivors have been recorded out of 138 confirmed infections in North America. One American survived the infection in 1978 and one individual from Mexico in 2003. In 2013, two children survived and recovered from primary amoebic meningoencephalitis after treatment with miltefosine. [37] [38] In 2016 after treatment that included miltefosine, another child became the fourth person in the United States to survive Naegleria fowleri infection. [39]

Society and culture

Availability

Since 2017 Miltefosine is commercially available in the United States through Profounda. [40] Previously one could only get it from the CDC for emergency use under an expanded access IND protocol for treatment of free-living amoeba (FLA) infections: primary amoebic meningoencephalitis caused by Naegleria fowleri and granulomatous amoebic encephalitis caused by Balamuthia mandrillaris and Acanthamoeba species. [37] Miltefosine is almost exclusively produced by Profounda, a private pharmaceutical company. [41]

Economics

In the developing world a course of treatment costs US$65 to $150. [6] In the developed world treatment may be 10 to 50 times greater. [6]

Further research

It is active against some bacteria and fungi, [3] [42] as well as human trematode Schistosoma mansoni and the snail that spreads it Biomphalaria alexandrina . [43]

Antiprotozoal and antifungal activities

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:

Anti-HIV activity

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. [56] [57] It significantly reduces replication of HIV-1 in cocultures of human dendritic cells (DCs) and CD4+ T cells, which is due to a rapid secretion of soluble factors and is associated with induction of type-I interferon (IFN) in the human cells. [58]

Related Research Articles

<span class="mw-page-title-main">Leishmaniasis</span> Disease caused by parasites of the Leishmania type

Leishmaniasis is a wide array of clinical manifestations caused by parasites of the Trypanosomatida genus Leishmania. It is generally spread through the bite of phlebotomine sandflies, Phlebotomus and Lutzomyia, and occurs most frequently in the tropics and sub-tropics of Africa, Asia, the Americas, and southern Europe. The disease can present in three main ways: cutaneous, mucocutaneous, or visceral. The cutaneous form presents with skin ulcers, while the mucocutaneous form presents with ulcers of the skin, mouth, and nose. The visceral form starts with skin ulcers and later presents with fever, low red blood cell count, and enlarged spleen and liver.

Free-living amoebae in the Amoebozoa group are important causes of disease in humans and animals.

<span class="mw-page-title-main">Naegleriasis</span> Rare and usually fatal brain infection by a protist

Naegleriasis is an almost invariably fatal infection of the brain by the free-living unicellular eukaryote Naegleria fowleri. Symptoms are meningitis-like and include headache, fever, nausea, vomiting, a stiff neck, confusion, hallucinations and seizures. Symptoms progress rapidly over around five days, and death usually results within one to two weeks of symptoms.

<i>Naegleria</i> Genus of protists

Naegleria is a free living amoebae protist genus consisting of 47 described species often found in warm aquatic environments as well as soil habitats worldwide. It has three life cycle forms: the amoeboid stage, the cyst stage, and the flagellated stage, and has been routinely studied for its ease in change from amoeboid to flagellated stages. The Naegleria genera became famous when Naegleria fowleri, a human pathogenic strain and the causative agent of primary amoebic meningoencephalitis (PAM), was discovered in 1965. Most species in the genus, however, are nonpathogenic, meaning they do not cause disease.

<span class="mw-page-title-main">Cutaneous leishmaniasis</span> Medical condition

Cutaneous leishmaniasis is the most common form of leishmaniasis affecting humans. It is a skin infection caused by a single-celled parasite that is transmitted by the bite of a phlebotomine sand fly. There are about thirty species of Leishmania that may cause cutaneous leishmaniasis.

<span class="mw-page-title-main">Visceral leishmaniasis</span> Human disease caused by protist parasites

Visceral leishmaniasis (VL), also known as kala-azar or "black fever", is the most severe form of leishmaniasis and, without proper diagnosis and treatment, is associated with high fatality. Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania.

<span class="mw-page-title-main">Sodium stibogluconate</span> Pharmaceutical drug

Sodium stibogluconate, sold under the brand name Pentostam among others, is a medication used to treat leishmaniasis. This includes leishmaniasis of the cutaneous, visceral, and mucosal types. Some combination of miltefosine, paramycin and liposomal amphotericin B, however, may be recommended due to issues with resistance. It is given by injection.

<span class="mw-page-title-main">Auranofin</span> Chemical compound

Auranofin is a gold salt classified by the World Health Organization as an antirheumatic agent. It has the brand name Ridaura.

<i>Balamuthia mandrillaris</i> Species of pathogenic Amoebozoa

Balamuthia mandrillaris is a free-living amoeba that causes the rare but deadly neurological condition granulomatous amoebic encephalitis (GAE). B. mandrillaris is a soil-dwelling amoeba and was first discovered in 1986 in the brain of a mandrill that died in the San Diego Wild Animal Park.

<span class="mw-page-title-main">Granulomatous amoebic encephalitis</span> Rare and usually fatal brain infection by certain amoebae

.

Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminths, amoeba, ectoparasites, parasitic fungi, and protozoa, among others. Antiparasitics target the parasitic agents of the infections by destroying them or inhibiting their growth; they are usually effective against a limited number of parasites within a particular class. Antiparasitics are one of the antimicrobial drugs which include antibiotics that target bacteria, and antifungals that target fungi. They may be administered orally, intravenously or topically. Overuse or misuse of antiparasitics can lead to the development of antimicrobial resistance.

<span class="mw-page-title-main">Nitroxoline</span> Antibiotic chemical compound

Nitroxoline is an antibiotic that has been in use in Europe for about fifty years, and has proven to be very effective at combating biofilm infections. Nitroxoline was shown to cause a decrease in the biofilm density of P. aeruginosa infections, which would allow access to the infection by the immune system in vivo. It was shown that nitroxoline functions by chelating Fe2+ and Zn2+ ions from the biofilm matrix; when Fe2+ and Zn2+ were reintroduced into the system, biofilm formation was reconstituted. The activity of biofilm degradation is comparable to EDTA, but has a history of human use in clinical settings and therefore has a precedent with which to allow its use against “slimy” biofilm infections.

The term "brain-eating amoeba" has been used to refer to several microorganisms:

<span class="mw-page-title-main">Protozoan infection</span> Parasitic disease caused by a protozoan

Protozoan infections are parasitic diseases caused by organisms formerly classified in the kingdom Protozoa. These organisms are now classified in the supergroups Excavata, Amoebozoa, Harosa, and Archaeplastida. They are usually contracted by either an insect vector or by contact with an infected substance or surface.

<i>Leishmania tropica</i> Species of protozoan parasite

Leishmania tropica is a flagellate parasite and the cause of anthroponotic cutaneous leishmaniasis in humans. This parasite is restricted to Afro-Eurasia and is a common cause of infection in Afghanistan, Iran, Syria, Yemen, Algeria, Morocco, and northern India.

Sappinia diploidea is a free-living amoeba species.

Cutaneous amoebiasis, refers to a form of amoebiasis that presents primarily in the skin. It can be caused by Acanthamoeba or Entamoeba histolytica. When associated with Acanthamoeba, it is also known as "cutaneous acanthamoebiasis". Balamuthia mandrillaris can also cause cutaneous amoebiasis, but can prove fatal if the amoeba enters the bloodstream It is characterized by ulcers. Diagnosis of amebiasis cutis calls for high degree of clinical suspicion. This needs to be backed with demonstration of trophozoites from lesions. Unless an early diagnosis can be made such patients can develop significant morbidity.

<span class="mw-page-title-main">Dehydroemetine</span> Chemical compound

Dehydroemetine is a synthetically produced antiprotozoal agent similar to emetine in its anti-amoebic properties and structure, but it produces fewer side effects. In the United States, it is manufactured by Roche.

<span class="mw-page-title-main">Post-kala-azar dermal leishmaniasis</span>

Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well. The rash usually starts around the mouth from where it spreads to other parts of the body depending on severity.

<i>Naegleria fowleri</i> Species of free-living excavate form of protist

Naegleria fowleri, colloquially known as the "brain-eating amoeba", is a species of the genus Naegleria. It belongs to the phylum Percolozoa and is technically classified as an amoeboflagellate excavate, rather than a true amoeba. This free-living microorganism primarily feeds on bacteria but can become pathogenic in humans, causing an extremely rare, sudden, severe, and usually fatal brain infection known as naegleriasis or primary amoebic meningoencephalitis (PAM).

References

  1. ↑ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 Oct 2023.
  3. 1 2 3 4 Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ (November 2012). "Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis". The Journal of Antimicrobial Chemotherapy. 67 (11): 2576–2597. doi: 10.1093/jac/dks275 . PMID   22833634.
  4. 1 2 3 4 5 American Society of Health-System Pharmacists (26 February 2016). "Miltefosine Monograph for Professionals". www.drugs.com. Archived from the original on 17 November 2016. Retrieved 16 November 2016.
  5. 1 2 "FDA approves Impavido to treat tropical disease leishmaniasis". U.S. Food and Drug Administration (FDA) (Press release). 19 March 2014. Archived from the original on 3 September 2014. Retrieved 30 August 2014.
  6. 1 2 3 World Health Organization (March 2010). Control of the leishmaniasis: report of a meeting of the WHO Expert Committee on the Control of Leishmaniases. World Health Organization. pp. 59, 88, 186. hdl:10665/44412. ISBN   9789241209496.
  7. ↑ Greenwood D (2008). Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph. OUP Oxford. p. 310. ISBN   9780199534845. Archived from the original on 2017-09-10.
  8. ↑ Kumar A (2013). Leishmania and Leishmaniasis. Springer Science & Business Media. p. 39. ISBN   9781461488699. Archived from the original on 2017-09-10.
  9. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  10. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  11. ↑ Cristina M, Pedrosa R (September 2005). "Hospital de Doenças Tropicais testa droga contra calazar". Sapiência (in Portuguese). Fundação de Amparo à Pesquisa do Estado do Piauí. Archived from the original on 2006-08-22. Retrieved 2006-09-01.
  12. ↑ Soto J, Berman J (December 2006). "Treatment of New World cutaneous leishmaniasis with miltefosine". Transactions of the Royal Society of Tropical Medicine and Hygiene. 100 (Suppl 1): S34–S40. doi:10.1016/j.trstmh.2006.02.022. PMID   16930649.
  13. ↑ "19th WHO Model List of Essential Medicines" (PDF). WHO. 2015. Archived (PDF) from the original on 13 May 2015. Retrieved 8 November 2016.
  14. ↑ Berman J (November 2005). "Clinical status of agents being developed for leishmaniasis". Expert Opinion on Investigational Drugs. 14 (11): 1337–1346. doi:10.1517/13543784.14.11.1337. PMID   16255674. S2CID   27189092.
  15. ↑ Linam WM, Ahmed M, Cope JR, Chu C, Visvesvara GS, da Silva AJ, et al. (March 2015). "Successful treatment of an adolescent with Naegleria fowleri primary amebic meningoencephalitis". Pediatrics. 135 (3): e744–e748. doi:10.1542/peds.2014-2292. PMC   4634363 . PMID   25667249.
  16. ↑ "Profounda Inc. receives FDA orphan-drug designation for the Treatment of Primary Amebic Meningoencephalitis (PAM) with Miltefosine". Profounda Inc. (Press release). Archived from the original on 2016-12-22. Retrieved 2017-05-25– via www.prnewswire.com.
  17. ↑ "FDA Orphan Drug Designation Granted to Profounda Inc. for the treatment of Acanthamoeba Keratitis with miltefosine". Profounda Inc. Archived from the original on 2016-12-21. Retrieved 2017-05-25– via www.prnewswire.com.
  18. ↑ "New FDA Pregnancy Categories Explained". Drugs.com. Archived from the original on 2016-11-16. Retrieved 2016-11-16.
  19. ↑ "Impavido- miltefosine capsule". DailyMed. Profounda, Inc. 5 June 2019. Retrieved 26 December 2019.
  20. ↑ Sindermann H, Engel J (December 2006). "Development of miltefosine as an oral treatment for leishmaniasis". Transactions of the Royal Society of Tropical Medicine and Hygiene. 100 (Suppl 1): S17–S20. doi:10.1016/j.trstmh.2006.02.010. PMID   16730362.
  21. 1 2 "Miltefosine Side Effects in Detail". Drugs.com. Archived from the original on 2016-11-17. Retrieved 2016-11-16.
  22. ↑ Seth SD (2008). "Drug therapy of leishmaniasis". In Seth SD (ed.). Textbook of Pharmacology. Elsevier India. p. 31. ISBN   9788131211588. Archived from the original on 2017-09-10.
  23. ↑ "Impavido New FDA Drug Approval". CenterWatch. Archived from the original on 2016-11-04. Retrieved 2016-11-09.
  24. ↑ "Miltefosine (Impravido) for the Treatment of Visceral, Mucosal and Cutaneous Leishmaniasis" (PDF). U.S. Food and Drug Administration. Archived (PDF) from the original on 2016-10-24. Retrieved 9 November 2016.
  25. ↑ Cohen J, Powderly WG, Opal SM (2016). Infectious Diseases. Elsevier Health Sciences. p. 1367. ISBN   9780702063381. Archived from the original on 2017-09-10.
  26. ↑ Teshima K, Ikeda K, Hamaguchi K, Hayashi K (July 1983). "Bindings of cobra venom phospholipases A2 to micelles of n-hexadecylphosphorylcholine". Journal of Biochemistry. 94 (1): 223–232. doi:10.1093/oxfordjournals.jbchem.a134333. PMID   6619110.
  27. ↑ Fleer EA, Unger C, Kim DJ, Eibl H (November 1987). "Metabolism of ether phospholipids and analogs in neoplastic cells". Lipids. 22 (11): 856–861. doi:10.1007/bf02535544. PMID   3444378. S2CID   4055850.
  28. ↑ Berger MR, Petru E, Schmähl D (1987). "Therapeutic ratio of mono or combination bacterial lipopolysaccharide therapy in methylnitrosourea-induced rat mammary carcinoma". Journal of Cancer Research and Clinical Oncology. 113 (5): 437–445. doi:10.1007/bf00390037. PMID   3624299. S2CID   21064546.
  29. ↑ Muschiol C, Berger MR, Schuler B, Scherf HR, Garzon FT, Zeller WJ, et al. (November 1987). "Alkyl phosphocholines: toxicity and anticancer properties". Lipids. 22 (11): 930–934. doi:10.1007/bf02535558. PMID   3444388. S2CID   24008282.
  30. ↑ Berger MR, Muschiol C, Schmähl D, Eibl HJ (December 1987). "New cytostatics with experimentally different toxic profiles". Cancer Treatment Reviews. 14 (3–4): 307–317. doi:10.1016/0305-7372(87)90023-5. PMID   3440252.
  31. ↑ Eibl H, Unger C (September 1990). "Hexadecylphosphocholine: a new and selective antitumor drug". Cancer Treatment Reviews. 17 (2–3): 233–242. doi:10.1016/0305-7372(90)90053-i. hdl: 11858/00-001M-0000-0013-0D40-8 . PMID   2272038.
  32. ↑ Hilgard P, Stekar J, Voegeli R, Engel J, Schumacher W, Eibl H, et al. (September 1988). "Characterization of the antitumor activity of hexadecylphosphocholine (D 18506)". European Journal of Cancer & Clinical Oncology. 24 (9): 1457–1461. doi:10.1016/0277-5379(88)90336-7. PMID   3141197.
  33. ↑ Croft SL, Neal RA, Pendergast W, Chan JH (August 1987). "The activity of alkyl phosphorylcholines and related derivatives against Leishmania donovani". Biochemical Pharmacology. 36 (16): 2633–2636. doi:10.1016/0006-2952(87)90543-0. PMID   3606662.
  34. ↑ Kuhlencord A, Maniera T, Eibl H, Unger C (August 1992). "Hexadecylphosphocholine: oral treatment of visceral leishmaniasis in mice". Antimicrobial Agents and Chemotherapy. 36 (8): 1630–1634. doi:10.1128/AAC.36.8.1630. PMC   192021 . PMID   1329624.
  35. ↑ Sundar S, Rosenkaimer F, Makharia MK, Goyal AK, Mandal AK, Voss A, et al. (December 1998). "Trial of oral miltefosine for visceral leishmaniasis". Lancet. 352 (9143): 1821–1823. doi: 10.1016/S0140-6736(98)04367-0 . PMID   9851383. S2CID   33761492.
  36. ↑ Centers for Disease Control and Prevention (CDC) (August 2013). "Investigational drug available directly from CDC for the treatment of infections with free-living amebae". MMWR. Morbidity and Mortality Weekly Report. 62 (33): 666. PMC   4604798 . PMID   23965830. Archived from the original on 2017-07-11.
  37. 1 2 "Naegleria fowleri - Primary Amebic Meningoencephalitis (PAM)". Centers for Disease Control and Prevention. 2014. Archived from the original on 14 February 2015. Retrieved 29 August 2014.
  38. ↑ Gholipour B (14 August 2013). "Brain-Eating Amoeba: How One Girl Survived". livescience. Archived from the original on 3 October 2014. Retrieved 29 August 2014.
  39. ↑ Goldschmidt D, Scutti S. "Rare recovery: Florida teen survives brain-eating amoeba". CNN. Archived from the original on 24 August 2016. Retrieved 23 August 2016.
  40. ↑ "Profounda, Inc. launches Impavido (miltefosine), the first and only oral Rx treatment for visceral, mucosal and cutaneous leishmaniasis, in the United States". Profounda Inc. (Press release). Archived from the original on 2017-03-16. Retrieved 2017-05-25– via www.prnewswire.com.
  41. ↑ Wessel L (17 September 2016). "A life-saving drug that treats a rare infection is almost impossible to find". Business Insider . Archived from the original on 2016-09-19. Retrieved 2016-11-01.
  42. ↑ Pachioni J, Magalhães JG, Lima EJ, Bueno L, Barbosa JF, de Sá MM, Rangel-Yagui CO (2013). "Alkylphospholipids - a promising class of chemotherapeutic agents with a broad pharmacological spectrum". Journal of Pharmacy & Pharmaceutical Sciences. 16 (5): 742–759. doi: 10.18433/J3CW23 . PMID   24393556.
  43. ↑ Eissa MM, El Bardicy S, Tadros M (May 2011). "Bioactivity of miltefosine against aquatic stages of Schistosoma mansoni, Schistosoma haematobium and their snail hosts, supported by scanning electron microscopy". Parasites & Vectors. 4 (1): 73. doi: 10.1186/1756-3305-4-73 . PMC   3114006 . PMID   21569375.
  44. ↑ Saraiva VB, Gibaldi D, Previato JO, Mendonça-Previato L, Bozza MT, Freire-De-Lima CG, Heise N (November 2002). "Proinflammatory and cytotoxic effects of hexadecylphosphocholine (miltefosine) against drug-resistant strains of Trypanosoma cruzi". Antimicrobial Agents and Chemotherapy. 46 (11): 3472–3477. doi:10.1128/AAC.46.11.3472-3477.2002. PMC   128733 . PMID   12384352.
  45. ↑ Widmer F, Wright LC, Obando D, Handke R, Ganendren R, Ellis DH, Sorrell TC (February 2006). "Hexadecylphosphocholine (miltefosine) has broad-spectrum fungicidal activity and is efficacious in a mouse model of cryptococcosis". Antimicrobial Agents and Chemotherapy. 50 (2): 414–421. doi:10.1128/AAC.50.2.414-421.2006. PMC   1366877 . PMID   16436691.
  46. ↑ Blaha C, Duchêne M, Aspöck H, Walochnik J (February 2006). "In vitro activity of hexadecylphosphocholine (miltefosine) against metronidazole-resistant and -susceptible strains of Trichomonas vaginalis". The Journal of Antimicrobial Chemotherapy. 57 (2): 273–278. doi: 10.1093/jac/dki417 . PMID   16344287.
  47. ↑ Choubey V, Maity P, Guha M, Kumar S, Srivastava K, Puri SK, Bandyopadhyay U (February 2007). "Inhibition of Plasmodium falciparum choline kinase by hexadecyltrimethylammonium bromide: a possible antimalarial mechanism". Antimicrobial Agents and Chemotherapy. 51 (2): 696–706. doi:10.1128/AAC.00919-06. PMC   1797733 . PMID   17145794.
  48. ↑ Schuster FL, Guglielmo BJ, Visvesvara GS (2006). "In-vitro activity of miltefosine and voriconazole on clinical isolates of free-living amebas: Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria fowleri". The Journal of Eukaryotic Microbiology. 53 (2): 121–126. doi:10.1111/j.1550-7408.2005.00082.x. PMID   16579814. S2CID   25517350.
  49. ↑ Kim JH, Jung SY, Lee YJ, Song KJ, Kwon D, Kim K, et al. (November 2008). "Effect of therapeutic chemical agents in vitro and on experimental meningoencephalitis due to Naegleria fowleri". Antimicrobial Agents and Chemotherapy. 52 (11): 4010–4016. doi:10.1128/AAC.00197-08. PMC   2573150 . PMID   18765686.
  50. ↑ Ahmad AF, Heaselgrave W, Andrew PW, Kilvington S (2013). "The in vitro efficacy of antimicrobial agents against the pathogenic free-living amoeba Balamuthia mandrillaris". The Journal of Eukaryotic Microbiology. 60 (5): 539–543. doi:10.1111/jeu.12062. PMID   23869955. S2CID   12941376.
  51. ↑ Rijal S, Ostyn B, Uranw S, Rai K, Bhattarai NR, Dorlo TP, et al. (June 2013). "Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance". Clinical Infectious Diseases. 56 (11): 1530–1538. doi: 10.1093/cid/cit102 . PMID   23425958.
  52. ↑ Rai K, Cuypers B, Bhattarai NR, Uranw S, Berg M, Ostyn B, et al. (October 2013). "Relapse after treatment with miltefosine for visceral leishmaniasis is associated with increased infectivity of the infecting Leishmania donovani strain". mBio. 4 (5): e00611–e00613. doi:10.1128/mBio.00611-13. PMC   3791894 . PMID   24105765.
  53. ↑ Dorlo TP, Rijal S, Ostyn B, de Vries PJ, Singh R, Bhattarai N, et al. (July 2014). "Failure of miltefosine in visceral leishmaniasis is associated with low drug exposure". The Journal of Infectious Diseases. 210 (1): 146–153. doi: 10.1093/infdis/jiu039 . PMID   24443541.
  54. ↑ Ostyn B, Hasker E, Dorlo TP, Rijal S, Sundar S, Dujardin JC, Boelaert M (2014). "Failure of miltefosine treatment for visceral leishmaniasis in children and men in South-East Asia". PLOS ONE. 9 (6): e100220. Bibcode:2014PLoSO...9j0220O. doi: 10.1371/journal.pone.0100220 . PMC   4062493 . PMID   24941345.
  55. ↑ Vila TV, Ishida K, de Souza W, Prousis K, Calogeropoulou T, Rozental S (January 2013). "Effect of alkylphospholipids on Candida albicans biofilm formation and maturation". The Journal of Antimicrobial Chemotherapy. 68 (1): 113–125. doi:10.1093/jac/dks353. PMID   22995097.
  56. ↑ Chugh P, Bradel-Tretheway B, Monteiro-Filho CM, Planelles V, Maggirwar SB, Dewhurst S, Kim B (January 2008). "Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy". Retrovirology. 5 (1): 11. doi: 10.1186/1742-4690-5-11 . PMC   2265748 . PMID   18237430.
  57. ↑ "Parasitic Drug Shows HIV-Fighting Promise". AIDSmeds.com. 2008-02-01. Archived from the original on 2008-02-12. Retrieved 2008-02-02.
  58. ↑ Garg R, Tremblay MJ (October 2012). "Miltefosine represses HIV-1 replication in human dendritic cell/T-cell cocultures partially by inducing secretion of type-I interferon". Virology. 432 (2): 271–276. doi: 10.1016/j.virol.2012.05.032 . PMID   22704066.
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