Sodium stibogluconate (Pentostam, Triostam) and meg-lumine antimonate (Glucantime), both pentavalent an-timonials, bind to sulfhydryl groups on proteins and may form thio antimonides. Some evidence suggests that the pentavalent form may be reduced in vivo to the trivalent antimonial before binding. Trivalent antimoni-als inhibit phosphofructokinase, a rate-limiting enzyme in glycolysis, and organisms whose growth is dependent on the anaerobic metabolism of glucose cannot survive without the active enzyme. Whether this is the mecha-nism by which pentavalent antimonials inhibit protozoa is unclear.
Antimonials are irritating to the intestinal mucosa and therefore are administered by intramuscular or slow intravenous injection. Peak blood concentrations occur in 2 hours. These drugs bind to cells, including erythrocytes, and are found in high concentrations in the liver and spleen. As compared with the trivalent an-timonials, which are no longer used, the pentavalent an-timonials bind to tissue less strongly. This results in higher blood levels, more rapid excretion, and lowered toxicity. Pentavalent antimonials are rapidly excreted in the urine, with up to one-half of the administered dose excreted in 24 hours.
No pentavalent antimonial is licensed for use, but sodium stibogluconate is available from the Parasitic Disease Drug Service of the Centers for Disease Control (CDC) for treatment of leishmaniasis. While the pentavalent antimony compounds can be given in-travenously or intramuscularly, local infiltration of the lesion in cutaneous leishmaniasis is highly effective. Because of the lower toxicity of liposomal amphotericin B, this drug is considered a first-line choice for vis-cerotropic leishmaniasis rather than the antimonials.
Adverse reactions particularly associated with the trivalent antimonials are coughing, occasional vomiting, myalgia, arthralgia, and changes in the electrocardio-gram. Sodium stibogluconate occasionally causes rashes, pruritus, abdominal pain, diarrhea, and anaphy-lactoid collapse. Liver damage with jaundice is a rare side effect. Toxic reactions are more common with re-peated courses of treatment. Biochemical evidence of pancreatitis is usual (97%), but severe or fatal pancre-atitis is extremely infrequent.