Meglumine antimoniate

The first reports on this approach were published independently by three different groups using liposomes as carriers of antimonial drugs like meglumine antimoniate in experimental leishmaniasis infection (Alving et al., 1978 Black et al., 1977 New et al., 1978). 

Valproic acid/salts Losartan Meglumine antimoniate Piroxicam Procainamide Salicylates Sodium stibogluconate Zalcitabine... 

Licochalcone (50) is a natural product that is isolated from the roots of Chinese liquorice and is reported to have antileishmanial activity [49]. A series of chromene-substituted chalcones related to licochalcone have been reported to have antileishmanial activity [50]. Compound 51 was reported to have an IC50 of 1.2 pM against Leishmania major promastigotes versus meglumine antimoniate (IC50 =30 pM). Various compounds related to 51 have potent antileishmanial activity (IC50 < 3 pM) with potency similar to 51, but they did not show cytotoxicity. 

Sodium stibogluconate (Pentostam) is an organic pentavalent antimony compound it may cause anorexia, vomiting, coughing and substemal pain. Used in mucocutaneous leishmaniasis, it may lead to severe irrflammation around pharyngeal or tracheal lesions which may require corticosteroid administration to control. Meglumine antimoniate is similar. 

Allopurinol has an antileishmanial effect in vitro and in animals, its effect being strongly increased by the addition of antimonial compounds. Allopurinol alone as well as in combination with meglumine antimoniate has been used in clinical studies. In a small study in patients with leishmaniasis and HIV infection, chnical and parasitological cure was achieved in four of five cases treated for 4 weeks, but in only one of the six treated for 3 weeks (1). 

Allopurinol and meglumine antimoniate (Glucantime) have been evaluated in a randomized controlled trial in 150 patients with cutaneous leishmaniasis (2). They received oral allopurinol (15 mg/kg/day) for 3 weeks or intramuscular meglumine antimoniate (30 mg/kg/day, corresponding to 8 mg/kg/day of pentavalent antimony, for 2 weeks), or combined therapy. There were a few adverse effects in those who used allopurinol nausea, heartburn (n = 3), and mild increases in transaminases (n = 2). These symptoms subsided on drug withdrawal. 

In an open study, 72 patients each received meglumine antimoniate (60 mg/kg/day) or allopurinol (20 mg/kg/day) plus low-dose meglumine antimoniate (30 mg/kg/day) for 20 days, and each was followed for 30 days after the end of treatment (3). Only six patients in the combined treatment group complained of mild abdominal pain and nausea however, one patient who received meglumine antimoniate developed a skin eruption. Generalized muscle pain and weakness occurred in four patients. 

Laguna F, Lopez-Velez R, Soriano V, Montilla P, Alvar J, Gonzalez-Lahoz JM. Assessment of allopurinol plus meglumine antimoniate in the treatment of visceral leishmaniasis in patients infected with HIV. J Infect 1994 28(3) 255-9. 

Esfandiarpour I, Alavi A. Evaluating the efficacy of allopurinol and meglumine antimoniate (Glucantime) in the treatment of cutaneous leishmaniasis. Int J Dermatol 2002 41(8) 521. ... 

Momeni AZ, Reiszadae MR, Aminjavaheri M. Treatment of cutaneous leishmaniasis with a combination of allopurinol and low-dose meglumine antimoniate. Int J Dermatol 2002 41(7) 441-3. 

A pharmacodynamic interaction has been described between amiodarone and meglumine antimoniate, both... 

Segura I, Garcia-Bolao I. Meglumine antimoniate, amiodarone and torsades de pointes a case report. Resuscitation 1999 42(l) 65-8. 

Meglumine antimoniate is a pentavalent antimonial chemically similar to sodium stibogluconate and is considered to have similar efficacy and toxicity. Meglutamine antimoniate solution contains pentavalent antimony 8.5% and stibogluconate 10%. 

The characteristics of 111 consecutive patients with visceral leishmaniasis in Sicily have been described (12). They were given intramuscular meglumine antimoniate (560 mg/m of pentavalent antimony), generally for 21 days. There were adverse effects in 16 patients, including rash (n = 3) and dry cough (n = 13). All the adverse effects bar one (a severe urticarial rash) were transient and self-limiting and did not require drug withdrawal. 

In a prospective, open trial, conventional treatment with sodium stibogluconate (n = 69) was compared with meglumine antimoniate (n = 58) for cutaneous Leishmania braziliensis (13). The trial was too small and of too short a duration to compare efficacy rehably, but... 

There has been a further comparison of meglumine antimoniate (n = 47) and sodium stibogluconate (n = 64) (14). The trial was too small to examine the efficacy of the two drugs, but there were more adverse events with sodium stibogluconate, with a greater proportion with raised transaminase and amylase activities. There were no differences in electrocardiographic abnormalities between the two groups. 

Autoimmune hemolytic anemia has been described with meglumine antimoniate (29). 

Hepatotoxicity has been described, but the disease itself may play an overriding role. In 16 patients with mucosal leishmaniasis treated with meglumine antimoniate 20 mg/ kg intravenously for 28 days, there were raised liver enzyme in conjunction with electrocardiographic abnormalities and/or musculoskeletal complaints in three subjects (SEDA-16, 311). 

Acute pancreatitis developed during treatment with meglumine antimoniate for visceral leishmaniasis in a young boy (31). 

A pharmacodynamic interaction has been described between amiodarone and meglumine antimoniate, both of which prolong the QT interval the interaction resulted in torsade de pointes (38). 

Saldanha AC, Romero GA, Merchan-Hamann E, Magalhaes AV, Macedo V de O. Estudo comparativo entre estibogluconato de sodio BP 88R e antimoniato de meglumina no tratamento da leishmaniose cutanea I. Eficacia e seguranca. [A comparative study between sodium stibogluconate BP 88R and meglumine antimoniate in the treatment of cutaneous leishmaniasis. I. The efficacy and safety.] Rev Soc Bras Med Trop 1999 32(4) 383-7. 

Kuyucu N, Kara C, Bakirtac A, Tezic T. Successful treatment of visceral leishmaniasis with aUopurinol plus ketoconazole in an infant who developed pancreatitis caused by meglumine antimoniate. Pediatr Infect Dis J 2001 20(4) 455-7. 

The introduction of tartar emetic (1) in 1912 for the treatment of mucocutaneous leishmaniasis heralded a new era in the treatment of the disease, which was followed by the investigation of a number of other antimonials for clinical efficacy in leishmaniasis. This led to the discovery of a number of fivevalent antimony compounds, that have laboratory and clinical efficacy and are better tolerated than tartar emetic. These included sodium stibogluconate (2), meglumine antimoniate (3), derivatives of stibanilic acid (stibamine, 4), stibacetin (5), ethyl stibamine (a mixture of 4, 5, antimonic acid and Et2NH in a molar ratio of 1 2 1 3 with 41-44% of fivevalent antimony content) and urea stibamine (6) have been used to treat kala-azar, cutaneous and mucocutaneous leishmaniasis in man. 

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