New Strategies for Control Forum : Chemotherapy

Abstract

In 1937 sodium antimonyl gluconate (‘Solustibosan’) was first used in the treatment of leishmaniasis in India and China 1,2 . It is a remarkable condemnation of our progress that fifty years later improved dosing regimens for the pentavalent antimonial derivatives of ‘Solubstibosan’, sodium stibogluconate (‘Pentostam’,Wellcome) and meglumine antimoniate (‘Glucantime’,Rhone-Poulenc), can still create such interest and be considered an advance. Despite the long courses, parenteral administration, difficulties in chemical synthesis and low activities against cutaneous disease, these pentavalent antimonials remain the first line treatment for leishmaniasis 3. Attempts to identify alternatives have produced a number of new drugs for the disease currently or about to undergo clinical trial. These include the pyrazolopyrimidines allopurinol and allopurinol riboside, the antifungal imidazole ketoconazole and the 4-methyl-8-aminoquinoline WR6026. Clinical evaluation of the compounds is not complete and whether they will replace the antimonials or be added to the ‘second line’ list along with pentamidine and amphotericin B is uncertain. Allopurinol may have a future in combination with ‘Pentostam’ 4, but along with it’s riboside derivative this drug has the pharmacokinetic problems of rapid excretion and metabolism by host xanthine oxidase.