Therapeutic drug monitoring of cycloserine and linezolid during anti-tuberculosis treatment in Beijing, China

SETTING: Plasma concentrations of cycloserine (CS) and linezolid (LZD) in tuberculosis (TB) patients are largely unknown. OBJECTIVE: To measure the plasma concentrations of CS and LZD after drug ingestion in drug-resistant TB patients. DESIGN: Patients who received CS and LZD as part of their treatment between 1 July 2012 and 1 July 2016 were studied retrospectively. CS and LZD plasma levels were determined using high-pressure liquid chromatography-tandem mass spectrometry. Plasma drug concentration, age, sex, liver disease, renal disease, administered doses and diabetes mellitus status were recorded. RESULTS: Based on 390 samples, CS plasma concentrations were below the lower limit of normal (54.87%, 214/390). There was a statistically significant difference between the low concentration group (14.0 ± 3.71 μg/ml) and the target concentration group (25.2 ± 3.73 μg/ml, P < 0.01). The mean plasma concentration of LZD was 15.6 ± 4.91 μg/ml, which was within the target concentration (12-26 μg/ml) in 65 patients. Variables that correlated with CS and LZD concentrations were not found in this retrospective study. CONCLUSION: Low plasma CS concentrations were common, while 83.1% (54/65) of plasma LZD concentrations were within the target range. Therapeutic drug monitoring is essential to maintain appropriate plasma drug concentrations in the era of precision medicine.