PRECLINICAL STUDIES OF THE SPECIFIC ACTIVITY OF THE NEW ANTITUBERCULOSIS DRUG THIOZONIDE

Abstract

In vitro and in vivo preclinical studies of the antituberculosis activity of thiozonide designed at the ZAO “Farn-Sintez” (Moscow) were conducted at the Central Research of Tuberculosis, Russian Academy of Medical Sciences. The in vitro study indicated that thiozonide exerted an antimycobacterial effect that was comparable with the inhibitory activity of isoniazid (INH) and rifampicin (RIF) suppressed the growth of a cultured virulent laboratory M. tuberculosis H37Rv strain that was susceptible to all antituberculosis drugs, a cultured M. tuberculosis CN-40 strain that was monoresistant to INH, and a cultured M. tuberculosis MS-115 strain that was multidrug resistant The in vivo study established that the survival of the experimental animals receiving thiozonide monotherapy did not differ from that of the animals given INH and RIF. Combined therapy with thiozonide and ethionamide (ETH) and that with thiozonide and pyrazinamide (PZA) versus PZA or ETH monotherapy caused a significant increase in the survival of the experimental animals in these groups. M. tuberculosis colonyforming units in the lung of the experimental mice taking thiozonide suggested that the drug administered in vivo in a dose of 25 mg/kg produced an effective antituberculous effect that was comparable with those in the lung of the animals receiving RIF in the same dose