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 INH, RMP and PZA were respectively 2.5, 4.0 and 43.6 μg/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 INH, 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.