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.