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

Abstract

Plasma concentrations of cycloserine (CS) and linezolid (LZD) in tuberculosis (TB) patients are largely unknown. To measure the plasma concentrations of CS and LZD after drug ingestion in drug-resistant TB patients. 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. 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. 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.