Miltefosine: a breakthrough in treatment of leishmaniasis

Authors

  • Arfan ul Bari

Keywords:

Miltefosine, leishmaniasis, anti-leishmanial drugs, anti-protozoal drugs

Abstract

The emergence of leishmaniasis strains resistant to pentavalent antimonials and the growing incidence of leishmaniasis among AIDS patients have made the availability of an oral agent extremely important for management of this disease. Miltefosine (hexadecylphosphocholine), an alkylphosphocholine, is an oral antiprotozoal drug that has recently been hailed as the first oral drug for the treatment of leishmaniasis, with the added advantage of being effective in patients, who had not responded to the standard antimonial drugs. It was initially developed as an oral drug for the treatment of cancer. Present article is an attempt to review different pharmacodyanamic, pharmacokinetic and therapeutic aspects of this new drug.

References

Herwaldt BL, Berman JD. Recommendations for treating leishmaniasis with sodium stibogluconate and review of pertinent clinical studies. Am J Trop Med Hyg 1992; 46: 296-306.

Bryceson A. A policy for leishmaniasis with respect to the prevention and control of drug resistance. Trop Med Int Health 2001; 6: 928-34.

Croft SL, Sundar S, Fairlamb AH. Drug resistance in leishmaniasis. Clin Microbiol Rev 2006; 19: 111-26.

Croft SL, Seifert K, Yardley V. Current scenario of drug development for leishmaniasis. Indian J Med Res 2006; 123: 399-410.

Alvar J, Croft S, Olliaro P. Chemotherapy in the treatment and control of leishmaniasis. Adv Parasitol 2006; 61: 223-74.

Sindermann H, Engel J. Development of miltefosine as an oral treatment for leishmaniasis. Trans R Soc Trop Med Hyg 2006 May 24; [Epub ahead of print]

Berman JD. Development of miltefosine for the leishmaniases. Mini Rev Med Chem 2006; 6: 145-51.

Soto J, Soto P. Miltefosine: oral treatment of leishmaniasis. Expert Rev Anti Infect Ther 2006; 4: 177-85.

Soto J, Arana BA, Toledo J et al. Miltefosine for new world cutaneous leishmaniasis. Clin Infect Dis 2004; 38: 1266-72.

Schraner C, Hasse B, Hasse U et al. Successful treatment with miltefosine of disseminated cutaneous leishmaniasis in a severely immunocompromised patient infected with HIV-1. Clin Infect Dis 2005; 40: e120-4.

Jendrossek V, Handrick R. Membrane targeted anticancer drugs: potent inducer of apoptosis and putative radiosesis. Curr Med Chem Anti-Canc Agents 2003; 3: 343-53.

Sunder S, Jha TK, Thakur CP et al. Oral Miltefosine for Indian Visceral leishmaniasis. N Engl J Med 2002; 347: 1739-46.

Hanson PK, Malone L, Birchmore JL, Nichols JW. Lem 3 p is essential for the uptake and potency of alkylphosphocholine drugs, edelfosine and miltefosine. J Biol Chem 2003; 5: 1324-31.

Lux H, Heise N, Klenner T, Hart D, Opperdoes FR. Ether–lipid (alkyl- phospholipid) matabolism and the mechanism of action of ether – lipid analogues in visceral leishmania. Mol Biochem Parasitol 2000; 111: 1-14.

Murray HW. Suppression of post treatment recurrence of experimental visceral leishmaniasis in t- cell- deficient mice by oral miltefosine. Antimicrob Agents Chemother 2000; 44: 3235-6.

Ruiter GA, Verheij M, Zerp SF, van Blitterswijk WJ. Alkyl-lysophospholipids as anticancer agents and enhancers of radiation-induced apoptosis. Int J Radiat Oncol Biol Phy 2001; 49: 415-9.

Jha TK, Sundar S, Thakur CP et al. Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis. N Engl J Med 1999; 341: 1795-800.

Bresiser A, Kim DJ, Fleer EA et al. Distribution and metabolism of hexadecylphosphocholine in mice. Lipids 1987; 22: 925-6.

Seifert K, Duchaene M, Werndorfer WH et al. Effects of miltefosine and other alkylphosphocholines on human intestinal parasite Entamoeba histolytica. Antimicrob Agents Chemother 2001; 45: 1505-10.

Mohan A, Seth S. Oral miltefosine in treatment of kala azar. Nat Med J Ind 2000; 13:202-3.

Thakur CP, Sinha PK, Singh KR et al. Miltefosine in a case of visceral leishmaniasis: and rising incidence of this disease in India. Trans R Soc Trop Med Hyg 2000; 94: 696-7.

Schmidt-Ott R, Klenner T, Overath P, Aebischer *. Topical treatment with heaxdecylphosphocholine (miltex) efficiently reduces parasite in experimental cutaneous leishmaniasis. Trans R Soc Trop Med Hyg 1999; 93: 85-90.

Konstantinov SM, Eibl H, Berger MR. BCR-ABL influences the antileukaemic efficacy of alkylphosphocholine. Br J Haematol 1999; 107: 365-80.

Konstantinov SM, Berger MR. Human urinary bladder carcinoma cell line respond to treatment with alkylphosphocholine. Cancer Lett 1999; 144: 153-60.

Verweij J, Gandia D, Planting AS et al. Phase II study of oral miltefosine in patients with squamous cell head and neck cancer. Eur J Cancer 1993; 29A: 778-9.

Verweij J, Planting AS, van der Burg M, Stoter G. A dose finding study of miltefosine (hexadecylphosphocholine) in patients with solid tumors. J Cancer Res Clin Oncol 1992; 188: 606-8.

Smorenburg CH, Seynaevec *, Bontenbal M et al. Phase II study of miltefosine 6% solution as topical treatment of skin metastases in breast cancer patients. Anticancer Drugs 2000; 11: 825-8.

Perez- Victoria FJ, Castanys S, Gamaroo F. Leishmania donovani resistance to miltefosine involves a defective inward translocation of the drug. Antimicrobiol Agents Chemother 2003; 47: 2397-403.

Sunder S, Jha TK, Sindermann H et al. Oral miltefosine in children with mild to moderate Indian visceral leishmanisis. Pediatr Infect Dis J 2003; 22: 434-8.

Prasad R, Kumar R, Jaiswal BP, Singh UK. Miltefosine: an oral drug for visceral leishmaniasis. Indian J Pediatr 2004; 71: 143-4.

Beckers T, Voegeli R, Hilgard P. Molecular and cellular effects of hexadecylphosphocholine (miltefosine) in human myeloid leukemic cell lines. Eur J Cancer 1994; 30D: 2143-50.

Sundar S, Gupta B, Makharia MK et al. Oral treatment of visceral leishmaniasis with miltefosine. Ann Trop Med Parasitol 1999: 93; 589-97

More B, Bhatt H, Kukreja V, Ainapure SS. Miltefosine: great expectations against visceral leishmaniasis. J Postgrad Med 2003; 49: 101-3.

Downloads

Published

2017-01-03

How to Cite

1.
Bari A ul. Miltefosine: a breakthrough in treatment of leishmaniasis. J Pak Assoc Dermatol [Internet]. 2017Jan.3 [cited 2025Jan.18];16(4):225-30. Available from: https://www.jpad.com.pk/index.php/jpad/article/view/884

Issue

Section

Review Articles

Most read articles by the same author(s)

1 2 3 4 5 > >>