Isoniazid, rifampicin and pyrazinamide plasma concentrations 2 and 6 h post dose in patients with pulmonary tuberculosis

BACKGROUND: Low concentrations of anti-tuberculosis drugs are related to drug resistance and treatment failure. OBJECTIVE: To determine the prevalence of low plasma concentrations of anti-tuberculosis drugs. METHODS: The study was performed among 60 pulmonary tuberculosis (TB) in-patients at a tertiary care university-affiliated hospital in Tehran, Iran. Drug samples were drawn 2 and 6 h post dose for isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA); related concentrations were determined using high-performance liquid chromatography. Plasma drug concentrations, duration of treatment, age, sex, liver enzyme levels, administered doses and smoking status were evaluated and recorded. RESULTS: Among 60 patients recruited to the study, the mean (+/- SD) age was 54.2 (+/- 20.9) years; 39 were female. The median peak plasma concentrations (C-max) of INTH, RMP and PZA were respectively 2.5, 4.0 and 43.6 mu g/ml; 81% of the patients had drug plasma concentrations lower than the target ranges for at least one administered drug. Respectively 49.1%, 92.5% and 8.7% of the patients had low concentrations of IN-H, RMP and PZA. CONCLUSION: The results indicate that RMP concentrations are below the reference range in most patients, while PZA is within the target range of the standard doses.