Predictors of therapeutic exposure and pharmacokinetic variability of second-line anti-TB drugs in MDR-TB patients: a retrospective study
Abstract
BACKGROUND: Therapeutic drug monitoring (TDM) is increasingly recommended for managing multidrug-resistant tuberculosis (MDR-TB) due to significant interindividual pharmacokinetic variability. However, data on plasma concentration variability and associated patient factors for second-line anti-TB drugs remain limited.
METHODS: We conducted a retrospective observational study including 74 patients with MDR-TB at West China Hospital, Sichuan University, from January 2022 to December 2024. Plasma concentrations of second-line drugs (levofloxacin, cycloserine, clofazimine, bedaquiline, and linezolid) were measured at steady-state. We analyzed therapeutic target attainment rates, evaluated correlations between drug concentrations and patient baseline characteristics, and explored predictors of drug exposure using multivariable linear regression.
RESULTS: Significant interindividual variability in drug exposure was observed across the studied second-line anti-TB drugs. Clofazimine demonstrated the highest therapeutic target attainment (72.7%), while bedaquiline had the lowest (21.1%). For levofloxacin, 29.8% of patients achieved therapeutic concentrations, whereas cycloserine reached target levels in 43.2% of cases. Age was positively correlated with cycloserine concentrations (ρ = 0.328, p = 0.030). Multivariable regression identified age and liver enzymes (ALT and AST) as independent predictors of levofloxacin exposure. Specifically, elevated ALT was associated with lower…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 74 participants or records.
Read the paper
Related studies
- Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
- Photochemical behavior of levofloxacin
- Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose/ Fluid Volume Ratio
- Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides
- Synthesis of [11C]levofloxacin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.