Antonenko P. An influence of polymorphism of drugs’ biotransformation on effectiveness of antituberculosis chemotherapy in human

Present work is dedicated to the research of an influence of genetic differences of the patients with pulmonary tuberculosis, which linked with biotransformation of the first-line antituberculosis drugs, and genetics of M.tuberculosis, which determine drug-resistance, on the effectiveness and safety of treatment. It was established that according to NAT2 and CYP2C9 genotypes in “slow acetylators” and “slow metabolizers” it was found higher isoniazid concentration in blood of TB-patients, better effectiveness and higher toxicity of tuberculosis treatment as well as lower risk of multidrug resistance development in M.tuberculosis strains than in “rapid acetylators” and “rapid metabolizers”. Considering CYP2C9 and CYP2Е1 genotypes in “slow metabolizers” it has been detected higher rifampicin concentration and toxicity of tuberculosis treatment than in “rapid metabolizers”. The detection of CYP2C9, CYP2Е1, and NAT2 in tuberculosis patients allows to reveal a group of patients with high risk of multiresistant strains appearing and development of hepatotoxicity that helps to increase an effectiveness and safety of tuberculosis treatment.