A Clinical Trial of Ethionamide and Prothionamide for Treatment of Lepromatous Leprosy

Abstract

In 1982-1984 we conducted a six-month clinical trial in 50 previously untreated lepromatous leprosy patients randomly assigned to directly observed monotherapy with one of two thioamides, ethionamide or prothionamide, each given six times a week at doses of either 250 mg or 500 mg. The findings of this study have only recently been analyzed, and the potential for the use of these thioamides in leprosy patients placed in perspective. However, because of the small number of patients included in this study, the results must be interpreted with some caution. Clinical improvement was noted in 74% of the patients treated with ethionamide and in 83% of those treated with prothionamide. Therapy was well tolerated and drug-related hepatotoxicity did not require discontinuation of therapy. The 500-mg dose of both ethionamide and prothionamide resulted in loss in Mycobacterium leprae viability more rapidly than did the 250-mg dose, and prothionamide at both dose levels was superior to the equivalent dose of ethionamide. Overall killing of M. leprae in this study was found to be similar to that obtained previously with dapsone and clofazimine, but less than was obtained with rifampin, minocycline, clarithromycin, pefloxacin, and ofloxacin.

The Thioamides Methimazole and Thiourea Inhibit Growth of M. avium Subspecies paratuberculosis in Culture

“…It is of considerable interest that the thioamides ethionamide and prothionamide are used in the therapy of leprosy, tuberculosis and M. avium complex infections diseases[14], [15], and thiourea isoxyl is active against M. tb . [16] Additionally both of the antithyrotoxic medications Methimazole and Propothiouricil inhibit M. leprae in the mouse footpad model [17]–[19]…”

Mechanism of thioamide drug action against tuberculosis and leprosy

“…Thioamide drugs, ethionamide (ETH) and prothionamide (PTH), have been widely used for many years in the treatment of mycobacterial infections caused by Mycobacterium tuberculosis , M. leprae , and M. avium complex infections ( 1 , 2 ). ETH and PTH are both bacteriocidal and are essentially interchangeable in a chemotherapy regimen.…”

Synthesis of 3-chloro-4-fluorophenyl-3,4-dichlorophenyl substituted thiocarbamide derivatives as potential antitubercular agents

“…Thioamide-containing drugs, Ethionamide (ETH) and Prothionamide (PTH), have been broadly used to control mycobacterial infections caused by Mycobacterium tuberculosis, M. leprae, and M. avium complex infections (Fajardo et al, 2006 andYajko et al, 1987). ETH and PTH are both bactericidal, and they are the most frequently used drugs for the treatment of drug-resistant TB and, therefore, are becoming increasingly relevant as the number of multidrug-resistant and extensively drug-resistant cases worldwide (CDC, 2006 andCrofton et al, 1997).…”