Antimonials (Meglumine antimoniate, Sodium stibogluconate)

Class

Organometallic pentavalent antimonials (SbV; Figure 1).

Antiparasitic Activity

Pentavalent antimonials are effective in vitro against all Leishmania species.

Mechanism of Action

Pentavalent antimonials bind to polypeptides, inhibit DNA topoisomerase glycolytic enzymes and fatty acid beta-oxidation. Electron microscopy studies show antimonial-induced changes in parasite cell membranes.

Mechanism of Resistance

The mechanism of resistance to the antimonials is unknown

Pharmacokinetics

Sodium stibogluconate and meglumine antimoniate are not absorbed orally. In humans, an injection of 10 mg/kg i.m. achieves peak levels of ~10 mg/L 2 hours after injection. Most of the antimony is eliminated rapidly, mainly via the urine.

Dosage

The recommended daily dose is 20 mg/kg/day but resistance may warrant higher doses which may lead to toxicity. This regime may be insufficient for children.

Pregnancy

Data on the safety of pentavalent antimonials in pregnancy are confined to case reports, which indicate antimonials to be safe.

Adverse Effects

Serious antimonial toxicity is usually reversible and includes elevation of serum amylase and liver enzymes, arthralgia and myalgia, thrombocytopenia, leukopoenia, anorexia and thrombophlebitis. Patients may complain of lethargy, headache, nausea, vomiting, metallic taste, or pruritus.

Drug Interactions

No interactions are known, but drugs which may impair renal function or prolong the QT interval should be used with caution.

Brand names/Manufacturer

Sodium stibogluconate: Pentostam™ (Glaxo SmithKline).

Meglumine antimoniate: Glucantime™.