ABSTRACT
Interactions of different drugs commonly used in multiple drug therapy were evaluated using both in vitro culture (cell-free as well as macrophage) system and mouse footpad. No additive effects were obtained in the in vitro system when dapsone was combined with either rifampicin or clofazimine, while a strong antagonism was observed when clofazimine was combined with rifampicin but not with rifabutin. In the mouse footpad system, a strong synergism was obtained when clofazimine was combined with either rifampicin or rifabutin, but significant antagonism was observed with the combination of clofazimine and dapsone.
Subject(s)
Animals , Clofazimine/pharmacology , Culture Media , Dapsone/pharmacology , Drug Interactions , Drug Therapy, Combination , Leprostatic Agents/pharmacology , Leprosy/drug therapy , Mice , Microbial Sensitivity Tests , Mycobacterium leprae/drug effects , Rifabutin , Rifampin/pharmacology , Rifamycins/pharmacologyABSTRACT
The new in vitro screening system reported earlier was adopted to determine anti-M. leprae activity of a dihydrofolate reductase inhibitor, brodimoprim, and the results were compared with those obtained using mouse foot-pad technique. Even though the MIC of brodimoprim against M. leprae was very high compared to other commonly used anti-leprosy drugs, in combination with dapsone it showed a remarkable synergistic activity in inhibiting the growth of M. leprae at concentrations much lower than the MICs of each of the drugs used singly. Similar effects were also demonstrated in mouse foot-pad experiments.