Miltefosine Explained

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.[1] This includes the three forms of leishmaniasis: cutaneous, visceral and mucosal. It may be used with liposomal amphotericin B or paromomycin. It is taken by mouth.[2]

Common side effects include vomiting, abdominal pain, fever, headaches, and decreased kidney function.[1] More severe side effects may include Stevens–Johnson syndrome or low blood platelets.[1] Use during pregnancy appears to cause harm to the baby and use during breastfeeding is not recommended.[1] How it works is not entirely clear.[1]

Miltefosine was first made in the early 1980s and studied as a treatment for cancer.[3] A few years later it was found to be useful for leishmaniasis and was approved for this use in 2002 in India.[4] It is on the World Health Organization's List of Essential Medicines.[5] [6]

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.[7] [8] This drug is now listed as a core medication for the treatment of leishmaniasis under the WHO Model List of Essential Medicines.[9] 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.[10]

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.[11] It has orphan drug status in the United States for acanthamoeba keratitis and primary amebic meningoencephalitis (PAM).[12] [13]

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.[14] 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.

Contraindications

Miltefosine is contraindicated in individuals who have a hypersensitivity to this medication, pregnant women, and people who have the Sjögren-Larsson syndrome.[15] 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.[16]

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.[17]

Serious side effects include rash, diarrhea, and arthritis. The side effects are more severe in women and young children. The overall effects are quite mild and easily reversed.[18]

Mechanism of action

Miltefosine primarily acts on Leishmania by affecting the species's promastigote and amastigote stages.[19] Miltefosine exerts its activity by interacting with lipids, inhibiting cytochrome c oxidase and causing apoptosis-like cell death.[20] This may affect membrane integrity and mitochondrial function of the parasite.

History

Cancer

While initially studied as a cancer medication, due to side effects it was never used for this purpose.[21]

Phospholipid group alkylphosphocholine were known since the early 1980s, particularly in terms of their binding affinity with cobra venom.[22] In 1987 the phospholipids were found to be potent toxins on leukemic cell culture.[23] Initial in vivo investigation on the antineoplastic activity showed positive result, but then only at high dosage and at high toxicity.[24] 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.[25] [26] 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.[27] [28]

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.[29] 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.[30] Results of the first clinical trial in humans were reported from Indian patients with chronic leishmaniasis with high degree of success and safety.[31] 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.[32]

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.[33] 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.[34] [35] In 2016 after treatment that included miltefosine, another child became the fourth person in the United States to survive Naegleria fowleri infection.[36]

Society and culture

Availability

Since 2017 Miltefosine is commercially available in the United States through Profounda.[37] 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. Miltefosine is almost exclusively produced by Profounda, a private pharmaceutical company.[38]

Economics

In the developing world a course of treatment costs US$65 to $150. In the developed world treatment may be 10 to 50 times greater.[39]

Further research

It is active against some bacteria and fungi,[40] as well as human trematode Schistosoma mansoni and the snail that spreads it Biomphalaria alexandrina.[41]

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.[54] [55] 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.[56]

External links

Notes and References

  1. Web site: American Society of Health-System Pharmacists. Miltefosine Monograph for Professionals. www.drugs.com. 16 November 2016. 26 February 2016. live. https://web.archive.org/web/20161117145201/https://www.drugs.com/monograph/miltefosine.html. 17 November 2016.
  2. FDA approves Impavido to treat tropical disease leishmaniasis. U.S. Food and Drug Administration (FDA). 30 August 2014. 19 March 2014. live. https://web.archive.org/web/20140903082843/https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm389671.htm. 3 September 2014.
  3. Book: Greenwood D . Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph. 2008. OUP Oxford. 978-0-19-953484-5. 310. live. https://web.archive.org/web/20170910151716/https://books.google.com/books?id=i4_FZHmzjzwC&pg=PA310. 2017-09-10.
  4. Book: Kumar A . Leishmania and Leishmaniasis. 2013. Springer Science & Business Media. 978-1-4614-8869-9. 39. live. https://web.archive.org/web/20170910151716/https://books.google.com/books?id=5eG5BAAAQBAJ&pg=PA39. 2017-09-10.
  5. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO . free .
  6. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 22nd list (2021) . 2021 . 10665/345533 . World Health Organization . World Health Organization . Geneva . WHO/MHP/HPS/EML/2021.02 . free .
  7. News: Cristina M, Pedrosa R . Hospital de Doenças Tropicais testa droga contra calazar . Sapiência . pt . Fundação de Amparo à Pesquisa do Estado do Piauí . September 2005 . 2006-09-01 . https://web.archive.org/web/20060822060527/http://www.fapepi.pi.gov.br/sapiencia6/pesquisa3.php . 2006-08-22 .
  8. Soto J, Berman J . Treatment of New World cutaneous leishmaniasis with miltefosine . Transactions of the Royal Society of Tropical Medicine and Hygiene . 100 . Suppl 1 . S34–S40 . December 2006 . 16930649 . 10.1016/j.trstmh.2006.02.022 .
  9. Web site: 19th WHO Model List of Essential Medicines. WHO. 2015. 8 November 2016. live. https://web.archive.org/web/20150513043105/http://www.who.int/medicines/publications/essentialmedicines/EML2015_8-May-15.pdf. 13 May 2015.
  10. Berman J . Clinical status of agents being developed for leishmaniasis . Expert Opinion on Investigational Drugs . 14 . 11 . 1337–1346 . November 2005 . 16255674 . 10.1517/13543784.14.11.1337 . 27189092 .
  11. Linam WM, Ahmed M, Cope JR, Chu C, Visvesvara GS, da Silva AJ, Qvarnstrom Y, Green J . 6 . Successful treatment of an adolescent with Naegleria fowleri primary amebic meningoencephalitis . Pediatrics . 135 . 3 . e744–e748 . March 2015 . 25667249 . 4634363 . 10.1542/peds.2014-2292 .
  12. Profounda Inc. receives FDA orphan-drug designation for the Treatment of Primary Amebic Meningoencephalitis (PAM) with Miltefosine . Profounda Inc.. www.prnewswire.com. 2017-05-25. live. https://web.archive.org/web/20161222072200/http://www.prnewswire.com/news-releases/profounda-inc-receives-fda-orphan-drug-designation-for-the-treatment-of-primary-amebic-meningoencephalitis-pam-with-miltefosine-300379937.html. 2016-12-22.
  13. Web site: FDA Orphan Drug Designation Granted to Profounda Inc. for the treatment of Acanthamoeba Keratitis with miltefosine.. Profounda Inc.. www.prnewswire.com. 2017-05-25. live. https://web.archive.org/web/20161221002837/http://www.prnewswire.com/news-releases/fda-orphan-drug-designation-granted-to-profounda-inc-for-the-treatment-of-acanthamoeba-keratitis-with-miltefosine-300380273.html. 2016-12-21.
  14. Web site: New FDA Pregnancy Categories Explained . Drugs.com . 2016-11-16. live. https://web.archive.org/web/20161116163852/https://www.drugs.com/pregnancy-categories.html. 2016-11-16.
  15. Web site: Impavido- miltefosine capsule . DailyMed . Profounda, Inc. . 5 June 2019 . 26 December 2019.
  16. Sindermann H, Engel J . Development of miltefosine as an oral treatment for leishmaniasis . Transactions of the Royal Society of Tropical Medicine and Hygiene . 100 . Suppl 1 . S17–S20 . December 2006 . 16730362 . 10.1016/j.trstmh.2006.02.010 .
  17. Web site: Miltefosine Side Effects in Detail . Drugs.com . 2016-11-16. live. https://web.archive.org/web/20161117070506/https://www.drugs.com/sfx/miltefosine-side-effects.html. 2016-11-17.
  18. Book: Seth SD . Textbook of Pharmacology. 2008. Elsevier India. 978-81-312-1158-8. 31. Seth SD . Drug therapy of leishmaniasis. live. https://web.archive.org/web/20170910151716/https://books.google.com/books?id=51ozlZRBvQwC&pg. 2017-09-10.
  19. Web site: Impavido New FDA Drug Approval . CenterWatch . 2016-11-09. live. https://web.archive.org/web/20161104192249/http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/1311/impavido-miltefosine. 2016-11-04.
  20. Web site: Miltefosine (Impravido) for the Treatment of Visceral, Mucosal and Cutaneous Leishmaniasis. U.S. Food and Drug Administration . 9 November 2016. live. https://web.archive.org/web/20161024125444/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM371074.pdf. 2016-10-24.
  21. Book: Cohen J, Powderly WG, Opal SM . Infectious Diseases. 2016. Elsevier Health Sciences. 978-0-7020-6338-1. 1367. live. https://web.archive.org/web/20170910151716/https://books.google.com/books?id=Dhq3DAAAQBAJ&pg=PA1367. 2017-09-10.
  22. Teshima K, Ikeda K, Hamaguchi K, Hayashi K . Bindings of cobra venom phospholipases A2 to micelles of n-hexadecylphosphorylcholine . Journal of Biochemistry . 94 . 1 . 223–232 . July 1983 . 6619110 . 10.1093/oxfordjournals.jbchem.a134333 .
  23. Fleer EA, Unger C, Kim DJ, Eibl H . Metabolism of ether phospholipids and analogs in neoplastic cells . Lipids . 22 . 11 . 856–861 . November 1987 . 3444378 . 10.1007/bf02535544 . 4055850 .
  24. Berger MR, Petru E, Schmähl D . 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 . 1987 . 3624299 . 10.1007/bf00390037 . 21064546 .
  25. Muschiol C, Berger MR, Schuler B, Scherf HR, Garzon FT, Zeller WJ, Unger C, Eibl HJ, Schmähl D . 6 . Alkyl phosphocholines: toxicity and anticancer properties . Lipids . 22 . 11 . 930–934 . November 1987 . 3444388 . 10.1007/bf02535558 . 24008282 .
  26. Berger MR, Muschiol C, Schmähl D, Eibl HJ . New cytostatics with experimentally different toxic profiles . Cancer Treatment Reviews . 14 . 3–4 . 307–317 . December 1987 . 3440252 . 10.1016/0305-7372(87)90023-5 .
  27. Eibl H, Unger C . Hexadecylphosphocholine: a new and selective antitumor drug . Cancer Treatment Reviews . 17 . 2–3 . 233–242 . September 1990 . 2272038 . 10.1016/0305-7372(90)90053-i . free . 11858/00-001M-0000-0013-0D40-8 .
  28. Hilgard P, Stekar J, Voegeli R, Engel J, Schumacher W, Eibl H, Unger C, Berger MR . 6 . Characterization of the antitumor activity of hexadecylphosphocholine (D 18506) . European Journal of Cancer & Clinical Oncology . 24 . 9 . 1457–1461 . September 1988 . 3141197 . 10.1016/0277-5379(88)90336-7 .
  29. Croft SL, Neal RA, Pendergast W, Chan JH . The activity of alkyl phosphorylcholines and related derivatives against Leishmania donovani . Biochemical Pharmacology . 36 . 16 . 2633–2636 . August 1987 . 3606662 . 10.1016/0006-2952(87)90543-0 .
  30. Kuhlencord A, Maniera T, Eibl H, Unger C . Hexadecylphosphocholine: oral treatment of visceral leishmaniasis in mice . Antimicrobial Agents and Chemotherapy . 36 . 8 . 1630–1634 . August 1992 . 1329624 . 192021 . 10.1128/AAC.36.8.1630 .
  31. Sundar S, Rosenkaimer F, Makharia MK, Goyal AK, Mandal AK, Voss A, Hilgard P, Murray HW . 6 . Trial of oral miltefosine for visceral leishmaniasis . Lancet . 352 . 9143 . 1821–1823 . December 1998 . 9851383 . 10.1016/S0140-6736(98)04367-0 . 33761492 . free .
  32. Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ . Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis . The Journal of Antimicrobial Chemotherapy . 67 . 11 . 2576–2597 . November 2012 . 22833634 . 10.1093/jac/dks275 . free .
  33. Investigational drug available directly from CDC for the treatment of infections with free-living amebae . MMWR. Morbidity and Mortality Weekly Report . 62 . 33 . 666 . August 2013 . 23965830 . 4604798 . live . https://web.archive.org/web/20170711092614/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6233a4.htm . 2017-07-11 . Centers for Disease Control and Prevention (CDC) .
  34. Web site: Naegleria fowleri - Primary Amebic Meningoencephalitis (PAM). Centers for Disease Control and Prevention. 29 August 2014. 2014. live. https://web.archive.org/web/20150214042623/http://www.cdc.gov/parasites/naegleria/treatment.html. 14 February 2015.
  35. Web site: Gholipour B . Brain-Eating Amoeba: How One Girl Survived. livescience. 29 August 2014. 14 August 2013. live. https://web.archive.org/web/20141003131011/http://www.livescience.com/38897-how-to-survive-a-brain-eating-amoeba.html. 3 October 2014.
  36. News: Goldschmidt D, Scutti S . Rare recovery: Florida teen survives brain-eating amoeba. 23 August 2016. CNN. live. https://web.archive.org/web/20160824145826/http://www.cnn.com/2016/08/23/health/brain-eating-amoeba-florida-teen-survives/. 24 August 2016.
  37. Profounda, Inc. launches Impavido (miltefosine), the first and only oral Rx treatment for visceral, mucosal and cutaneous leishmaniasis, in the United States . Profounda Inc. . www.prnewswire.com. 2017-05-25. live. https://web.archive.org/web/20170316075853/http://www.prnewswire.com/news-releases/profounda-inc-launches-impavido-miltefosine-the-first-and-only-oral-rx-treatment-for-visceral-mucosal-and-cutaneous-leishmaniasis-in-the-united-states-300238867.html. 2017-03-16.
  38. Web site: Wessel L . 17 September 2016 . A life-saving drug that treats a rare infection is almost impossible to find . . 2016-11-01 . live . https://web.archive.org/web/20160919150218/http://www.businessinsider.com/why-brain-eating-amoeba-miltefosine-medicine-is-hard-to-find-2016-9?amp . 2016-09-19 .
  39. Book: Control of the leishmaniasis: report of a meeting of the WHO Expert Committee on the Control of Leishmaniases. March 2010. ((World Health Organization)) . World Health Organization . World Health Organization. 978-92-4-120949-6. 59, 88, 186 . 10665/44412.
  40. Pachioni J, Magalhães JG, Lima EJ, Bueno L, Barbosa JF, de Sá MM, Rangel-Yagui CO . Alkylphospholipids - a promising class of chemotherapeutic agents with a broad pharmacological spectrum . Journal of Pharmacy & Pharmaceutical Sciences . 16 . 5 . 742–759 . 2013 . 24393556 . 10.18433/J3CW23 . free .
  41. Eissa MM, El Bardicy S, Tadros M . 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 . May 2011 . 21569375 . 3114006 . 10.1186/1756-3305-4-73 . free .
  42. Saraiva VB, Gibaldi D, Previato JO, Mendonça-Previato L, Bozza MT, Freire-De-Lima CG, Heise N . Proinflammatory and cytotoxic effects of hexadecylphosphocholine (miltefosine) against drug-resistant strains of Trypanosoma cruzi . Antimicrobial Agents and Chemotherapy . 46 . 11 . 3472–3477 . November 2002 . 12384352 . 128733 . 10.1128/AAC.46.11.3472-3477.2002 .
  43. Widmer F, Wright LC, Obando D, Handke R, Ganendren R, Ellis DH, Sorrell TC . Hexadecylphosphocholine (miltefosine) has broad-spectrum fungicidal activity and is efficacious in a mouse model of cryptococcosis . Antimicrobial Agents and Chemotherapy . 50 . 2 . 414–421 . February 2006 . 16436691 . 1366877 . 10.1128/AAC.50.2.414-421.2006 .
  44. Blaha C, Duchêne M, Aspöck H, Walochnik J . In vitro activity of hexadecylphosphocholine (miltefosine) against metronidazole-resistant and -susceptible strains of Trichomonas vaginalis . The Journal of Antimicrobial Chemotherapy . 57 . 2 . 273–278 . February 2006 . 16344287 . 10.1093/jac/dki417 . free .
  45. Choubey V, Maity P, Guha M, Kumar S, Srivastava K, Puri SK, Bandyopadhyay U . Inhibition of Plasmodium falciparum choline kinase by hexadecyltrimethylammonium bromide: a possible antimalarial mechanism . Antimicrobial Agents and Chemotherapy . 51 . 2 . 696–706 . February 2007 . 17145794 . 1797733 . 10.1128/AAC.00919-06 .
  46. Schuster FL, Guglielmo BJ, Visvesvara GS . 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 . 2006 . 16579814 . 10.1111/j.1550-7408.2005.00082.x . 25517350 .
  47. Kim JH, Jung SY, Lee YJ, Song KJ, Kwon D, Kim K, Park S, Im KI, Shin HJ . 6 . Effect of therapeutic chemical agents in vitro and on experimental meningoencephalitis due to Naegleria fowleri . Antimicrobial Agents and Chemotherapy . 52 . 11 . 4010–4016 . November 2008 . 18765686 . 2573150 . 10.1128/AAC.00197-08 .
  48. Ahmad AF, Heaselgrave W, Andrew PW, Kilvington S . The in vitro efficacy of antimicrobial agents against the pathogenic free-living amoeba Balamuthia mandrillaris . The Journal of Eukaryotic Microbiology . 60 . 5 . 539–543 . 2013 . 23869955 . 10.1111/jeu.12062 . 12941376 .
  49. Rijal S, Ostyn B, Uranw S, Rai K, Bhattarai NR, Dorlo TP, Beijnen JH, Vanaerschot M, Decuypere S, Dhakal SS, Das ML, Karki P, Singh R, Boelaert M, Dujardin JC . 6 . 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 . June 2013 . 23425958 . 10.1093/cid/cit102 . free .
  50. Rai K, Cuypers B, Bhattarai NR, Uranw S, Berg M, Ostyn B, Dujardin JC, Rijal S, Vanaerschot M . 6 . Relapse after treatment with miltefosine for visceral leishmaniasis is associated with increased infectivity of the infecting Leishmania donovani strain . mBio . 4 . 5 . e00611–e00613 . October 2013 . 24105765 . 3791894 . 10.1128/mBio.00611-13 .
  51. Dorlo TP, Rijal S, Ostyn B, de Vries PJ, Singh R, Bhattarai N, Uranw S, Dujardin JC, Boelaert M, Beijnen JH, Huitema AD . 6 . Failure of miltefosine in visceral leishmaniasis is associated with low drug exposure . The Journal of Infectious Diseases . 210 . 1 . 146–153 . July 2014 . 24443541 . 10.1093/infdis/jiu039 . free .
  52. Ostyn B, Hasker E, Dorlo TP, Rijal S, Sundar S, Dujardin JC, Boelaert M . Failure of miltefosine treatment for visceral leishmaniasis in children and men in South-East Asia . PLOS ONE . 9 . 6 . e100220 . 2014 . 24941345 . 4062493 . 10.1371/journal.pone.0100220 . free . 2014PLoSO...9j0220O .
  53. Vila TV, Ishida K, de Souza W, Prousis K, Calogeropoulou T, Rozental S . Effect of alkylphospholipids on Candida albicans biofilm formation and maturation . The Journal of Antimicrobial Chemotherapy . 68 . 1 . 113–125 . January 2013 . 22995097 . 10.1093/jac/dks353 .
  54. Chugh P, Bradel-Tretheway B, Monteiro-Filho CM, Planelles V, Maggirwar SB, Dewhurst S, Kim B . Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy . Retrovirology . 5 . 1 . 11 . January 2008 . 18237430 . 2265748 . 10.1186/1742-4690-5-11 . free .
  55. Web site: Parasitic Drug Shows HIV-Fighting Promise . 2008-02-02 . 2008-02-01 . AIDSmeds.com . https://web.archive.org/web/20080212122209/http://www.aidsmeds.com/articles/hiv_miltefosine_macrophages_1667_13933.shtml . 2008-02-12 .
  56. Garg R, Tremblay MJ . 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 . October 2012 . 22704066 . 10.1016/j.virol.2012.05.032 . free .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Miltefosine".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.