Therapeutic monitoring of isoniazid, rifampicin, ethambutol and pyrazinamide serum levels in the treatment of active pulmonary tuberculosis and determinants of their serum concentrations

Inadequate serum levels of antimycobacterial drugs have been associated with treatment failure, relapse and acquired drug resistance as well as high concentrations of these drugs may cause intolerance and toxic effects. We objected in this study to determine serum concentrations of anti-tuberculosis drugs and to know the determinants of their concentrations. Venous blood samples was obtained 2 and 6 h after drug ingestion, and serum levels of drugs were analysed using high performance liquid chromatography. Among 49 enrolled active pulmonary tuberculosis patients, the prevalances of a low concentration of isoniazid, rifampicin, ethambutol and pyrazinamide were 28.6, 75.5, 18.4 and 20.4%, respectively. 2 h ısoniazid (INH) concentration was found to be associated with sex (p = 0.005), correlated with body mass index (r = -0.390) and associated with drug dose (mg/kg) (p = 0.000). By Independent samples t-test analysis, low 2 h rifampicin concentration was found to be associated with sex (p = 0.000) and smoking cigarette (p = 0.004). In conclusion, the results of this study have shown that, low 2 h serum INH and rifampicin (RIF) concentration are common and It may be  necessary to optimise drug doses by therapeutic drug monitoring.   Key words: Therapeutic drug monitoring, tuberculosis, isoniazid, rifampicin, ethambutol, pyrazinamide.