Study On The Pharmacodynamics Of Antituberculosis New Compound ATB107 In Vivo

Objective To study the pharmacodynamics of Compound ATB107 of antituberculosis drug, assess its activity against Mycobacterium tuberculosis (standard strains and INH-RFP resistant strains) in vivo.Methods A murine model of Mycobacterium tuberculosis (MTB) infection was established by injection with standard strain H37Rv or INH-RFP resistant strains of bacteria via the tail vein. There were three treatment groups, including isoniazid (INH), Compound ATB107, Compound ATB107 and isoniazid. The remedial period was 4 weeks. The control group was set up by injection normal saline (NS). The effect of drugs was assessed by body weight, mortality, the lung and spleen tissues histopathological changes (HE staining and acid-fast stain), and Organ MTB burden.Results In the experimental infection group of Standard strains H37Rv, Although the remedial effect of Compound ATB107 is not better than isoniazid and isoniazid combination with Compound ATB107, Compound ATB107 had less the pathological changes of organs and shown significant antituberculosis effect in vivo compare with the control group. Compared with the controls, the treatment groups reduced organ bacterial count (P < 0.05). The antituberculosis activity of the joint compound ATB107 treatment group was better than the alone isoniazid treatment group (P <0.05). In the experimental infection group of resistant strains, Compound ATB107 showed significant effect of anti-drug-resistant Mycobacterium tuberculosis. Comparing with the control group, the weight decrease and the pathological changes were not obvious, the experimental mice did not die of infection, the bacterial burdens (CFU) of lung and spleen were reduced significant (P <0.01).Conclusion Results of experiments of Compound ATB107 in vivo shown effectively antituberculosis activity. The joint ATB107-INH treatment was superior to the alone INH treatment. Compound ATB107 can be used as a potential drug candidate of combination therapy and anti-drug-resistant strains of Mycobacterium tuberculosis infection.