Sodium Stibogluconate (DB05630): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Sodium stibogluconate (SSG) is a pentavalent antimonial compound that has served as a cornerstone in the treatment of the parasitic disease leishmaniasis for over half a century.[1] First introduced into medical use in the 1940s, it has been the historical mainstay for all three clinical forms of the disease: visceral, cutaneous, and mucosal leishmaniasis.[3] The drug is administered parenterally and functions as a prodrug, requiring reduction to its active trivalent antimony form within host macrophages and the parasite itself to exert its leishmanicidal effects.[4] Its mechanism of action, while not fully elucidated, is believed to be multifactorial, involving the critical disruption of the parasite's energy metabolism through the inhibition of glycolysis and the citric acid cycle, leading to the depletion of adenosine triphosphate (ATP) and guanosine triphosphate (GTP) pools, as well as the inhibition of DNA topoisomerase I.[3]

Despite its historical importance, the clinical utility of sodium stibogluconate has been significantly eroded by the global emergence of widespread drug resistance, particularly in key endemic areas for visceral leishmaniasis, such as the Indian subcontinent.[5] This has led to its replacement with alternative therapies like liposomal amphotericin B and miltefosine in many first-line treatment guidelines.[7] Furthermore, the drug is associated with a significant and challenging safety profile. Common adverse effects include musculoskeletal pain, gastrointestinal disturbances, and biochemical abnormalities, while severe, life-threatening toxicities such as pancreatitis and cardiotoxicity—manifesting as electrocardiogram changes and potentially fatal arrhythmias—require rigorous clinical monitoring.[1]