One of the reasons for tuberculosis treatment failure is a low concentration of antituberculosis agents, including rifampicin in the patient’s organism. However, the researches dedicated to rifampicin concentration in TB-patients, are almost absent in Ukraine. That’s why the aim of the present work was an investigation of rifampicin concentration in TB-patients with consideration of genotype of cytochrome (CYP) 2C19 that can participate in rifampicin metabolism.
Materials and Methods. The CYP450 2C19 genotype was detected with the help of polymerase chain reaction (PCR) and endonuclease analysis. Rifampicin and isoniazid concentration were detected in venous blood 2, 4, 6 and 24 hrs after ingestion of standard doses with spectrophotometer. It has been calculated T1/2 (half-life) for isoniazid according to which the patients were divided into two groups — with rapid/intermediate biotransformation of isoniazid (R/IA) and with slow biotransformation (SA). The blood samples were obtained from patients with new cases of pulmonary TB from Odesa regional antituberculous dispensary in 2012.
Results. Among 80 TB-patients according to CYP2C19 genotype 77.5% individuals belong to rapid metabolizers (*1/*1), others — 22.5% — to intermediate metabolizers (*1/*2). One day after rifampicin intake the intermediate metabolizers exhibited under-effective rifampicin concentration 1.5 times as much frequently than rapid metabolizers (58.1% versus 88.9%; p=0.033). Also in TB-patients with CYP2C19*1/*1 genotype one can see 1.5 times as much often rapid/intermediate type of isoniazid biotransformation than among individuals with CYP2C19*1/*2 genotype. In carriers of CYP2C19*1/*1 genotype the rapid/intermediate type of isoniazid has been associated with more numbers of under-effective rifampicin concentration than in slow biotransformation.