Tags

Type your tag names separated by a space and hit enter

Orally effective drugs for kala-azar (visceral leishmaniasis): focus on miltefosine and sitamaquine.
J Assoc Physicians India. 2003 Jul; 51:686-90.JA

Abstract

Currently there are no effective orally administered drugs or visceral leishmaniasis or kala-azar, a parasitic disease affecting about 0.5 million people a year, majority of whom are in India and adjacent areas of Nepal. Symptoms of affected patients are fever, cachexia, hepatosplenomegaly and pancytopenia. The disease is usually fatal, if left untreated. Traditionally kala-azar is treated with four weeks of injections of sodium stibogluconate, a pentavalent antimonial. However, this treatment has not only shown resistance in 37-64% patients of the current Indian epidemic in Bihar (the epicentrre) but also life-threatening cardiotoxicity in 7-10% and treatment-related deaths in 5-10% cases, besides being unsuccessful at times. Parenteral amphotericin B is used as a secondary agent that shows 95% effectiveness but its toxicity and high cost of even the well tolerated liposomal complex precludes its wide use in the developing countries, where the disease is present in epidemic proportions. Recently, miltefosine (hexadecylphosphocholine), a compound originally developed as an antitumour agent has been shown to be an orally effective drugs against kala-azar. All clinical trials with this drug are conducted in India in patients of visceral leishmaniasis. A regimen of 100 mg per day or 50 mg twice daily for 3-4 weeks was observed to produce a cure rate of 100%. Gastrointestinal side effects were frequent (62%) but no patient discontinued the therapy. A phase III trial involving 300 HIV-negative adults and adolescents is underway in India and the drug is hoped to be licensed in the next 2-3 years. Few studies of phase II clinical trials mainly conducted in Kenya with another drug, sitamaquine or kalazaquine (WR 6026), an 8-aminoquinoline has also shown promise as an orally effective agent (in a dose of 1 mg/kg/day for two weeks) for visceral leishmaniasis. These Studies with two orally effective compounds, it appears, will open new vistas for orally effective, affordable and acceptable drugs in the armamentarium for the treatment of kala-azar. It is expected that in future we would have effective ways to prevent and treat all forms of leishmaniasis without discomforting the patient.

Authors+Show Affiliations

Department of Pharmacology, BP Koirala Institute of Health Sciences, Dharan, Nepal.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

14621038

Citation

Sangraula, H, et al. "Orally Effective Drugs for Kala-azar (visceral Leishmaniasis): Focus On Miltefosine and Sitamaquine." The Journal of the Association of Physicians of India, vol. 51, 2003, pp. 686-90.
Sangraula H, Sharma KK, Rijal S, et al. Orally effective drugs for kala-azar (visceral leishmaniasis): focus on miltefosine and sitamaquine. J Assoc Physicians India. 2003;51:686-90.
Sangraula, H., Sharma, K. K., Rijal, S., Dwivedi, S., & Koirala, S. (2003). Orally effective drugs for kala-azar (visceral leishmaniasis): focus on miltefosine and sitamaquine. The Journal of the Association of Physicians of India, 51, 686-90.
Sangraula H, et al. Orally Effective Drugs for Kala-azar (visceral Leishmaniasis): Focus On Miltefosine and Sitamaquine. J Assoc Physicians India. 2003;51:686-90. PubMed PMID: 14621038.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Orally effective drugs for kala-azar (visceral leishmaniasis): focus on miltefosine and sitamaquine. AU - Sangraula,H, AU - Sharma,K K, AU - Rijal,S, AU - Dwivedi,S, AU - Koirala,S, PY - 2003/11/19/pubmed PY - 2004/6/15/medline PY - 2003/11/19/entrez SP - 686 EP - 90 JF - The Journal of the Association of Physicians of India JO - J Assoc Physicians India VL - 51 N2 - Currently there are no effective orally administered drugs or visceral leishmaniasis or kala-azar, a parasitic disease affecting about 0.5 million people a year, majority of whom are in India and adjacent areas of Nepal. Symptoms of affected patients are fever, cachexia, hepatosplenomegaly and pancytopenia. The disease is usually fatal, if left untreated. Traditionally kala-azar is treated with four weeks of injections of sodium stibogluconate, a pentavalent antimonial. However, this treatment has not only shown resistance in 37-64% patients of the current Indian epidemic in Bihar (the epicentrre) but also life-threatening cardiotoxicity in 7-10% and treatment-related deaths in 5-10% cases, besides being unsuccessful at times. Parenteral amphotericin B is used as a secondary agent that shows 95% effectiveness but its toxicity and high cost of even the well tolerated liposomal complex precludes its wide use in the developing countries, where the disease is present in epidemic proportions. Recently, miltefosine (hexadecylphosphocholine), a compound originally developed as an antitumour agent has been shown to be an orally effective drugs against kala-azar. All clinical trials with this drug are conducted in India in patients of visceral leishmaniasis. A regimen of 100 mg per day or 50 mg twice daily for 3-4 weeks was observed to produce a cure rate of 100%. Gastrointestinal side effects were frequent (62%) but no patient discontinued the therapy. A phase III trial involving 300 HIV-negative adults and adolescents is underway in India and the drug is hoped to be licensed in the next 2-3 years. Few studies of phase II clinical trials mainly conducted in Kenya with another drug, sitamaquine or kalazaquine (WR 6026), an 8-aminoquinoline has also shown promise as an orally effective agent (in a dose of 1 mg/kg/day for two weeks) for visceral leishmaniasis. These Studies with two orally effective compounds, it appears, will open new vistas for orally effective, affordable and acceptable drugs in the armamentarium for the treatment of kala-azar. It is expected that in future we would have effective ways to prevent and treat all forms of leishmaniasis without discomforting the patient. SN - 0004-5772 UR - https://www.unboundmedicine.com/medline/citation/14621038/Orally_effective_drugs_for_kala_azar__visceral_leishmaniasis_:_focus_on_miltefosine_and_sitamaquine_ L2 - http://www.diseaseinfosearch.org/result/4166 DB - PRIME DP - Unbound Medicine ER -