Orally effective drugs for kala-azar (visceral leishmaniasis): focus on miltefosine and sitamaquine.
Article
em En
| IMSEAR
| ID: sea-86529
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.
Texto completo:
1
Índice:
IMSEAR
Assunto principal:
Fosforilcolina
/
Leishmania donovani
/
Humanos
/
Administração Oral
/
Ensaios Clínicos como Assunto
/
Leishmaniose Cutânea
/
Relação Dose-Resposta a Droga
/
Aminoquinolinas
/
Índia
/
Leishmaniose Visceral
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article