Analysis of influencing factors on the plasma concentration of first-line anti-tuberculosis drugs-a single-center retrospective cohort study

BACKGROUND: The four most commonly used first-line anti-tuberculosis (TB) drugs in clinical practice are isoniazid (INH), rifampicin (RFP), ethambutol (EMB), and pyrazinamide (PZA). The plasma concentration of anti-TB drugs is an important factor influencing the effectiveness of TB treatment. Factors affecting blood concentration of antituberculosis drugs have not been elaborated clearly. The purpose of this study is to investigate the status of plasma concentration of anti-TB drugs, explore the factors influencing anti-TB drug plasma concentration, and guide the rational use of clinical drugs. METHODS: This is a single-center retrospective cohort study. Patients with pulmonary TB received first-line anti-TB drugs in the 309th Hospital of the PLA from June 2014 to September 2018 were investigated. The primary endpoint was factors affecting the anti-tuberculosis drug plasma concentration which were determined by high performance liquid chromatography-mass spectrometry. The factors influencing plasma concentration analyzed by the multiple linear regression model. RESULTS: A total of 205 patients were included in the study. The rates of patients with substandard 2-hour plasma concentrations of INH, RFP, EMB, and PZA were 45.8%, 54.4%, 37.7%, and 52.9%, respectively. Intravenous administration of INH (P<0.001) significantly increased plasma concentrations compared with oral administration, and its plasma concentration was negatively correlated with blood uric acid levels (P=0.001). RFP 2-hour plasma concentrations were positively correlated with serum albumin levels (P=0.04). EMB 2-hour plasma concentrations were positively correlated with age (P=0.01), dose (P<0.001), and serum creatinine levels (P<0.001). PZA 2-hour plasma concentrations were positively correlated with dose (P<0.001) and total bilirubin levels (P<0.001), and were negatively correlated with blood urea nitrogen levels (P=0.001). CONCLUSIONS: Age, gender, dose, intravenous administration, retreatment, blood uric acid level, serum albumin level, serum creatinine level, total bilirubin level, and blood urea nitrogen level were independent influencing factors of anti-TB drug plasma concentration. During anti-TB treatment, plasma concentration monitoring is essential and helpful to optimize the drug dose and carry out individualized treatment regimen.