Abstract
Background: Pharmacokinetic data are needed for newly implemented anti-tuberculosis drugs to help optimize their use.
Objectives: To help fill existing knowledge gaps, we evaluated the pharmacokinetic parameters of novel and repurposed anti-tuberculosis drugs among patients with drug-resistant pulmonary tuberculosis.
Methods: A prospective cohort study among patients >= 16 years with confirmed pulmonary drug-resistant TB was conducted in Tbilisi, Georgia. Patients receiving bedaquiline, delamanid and/or clofazimine were included. Blood samples were collected 4-6 weeks after drug initiation, and serum concentrations were measured using validated liquid chromatography tandem mass spectrometry assays. A non-compartmental analysis was performed, and the association of exposure parameters with covariates was explored.
Results: Among 99 patients, the average age and weight were 40 years and 65 kg, respectively. The median C-min was 0.68 mg/L for bedaquiline, 0.17 mg/L for delamanid, and 0.52 mg/L for clofazimine. The median AUC(0-24 )was 30.6 mg.h/L for bedaquiline, 16.1 mg.h/L for clofazimine, and the AUC(0-12) was 2.9 mg.h/L for delamanid. Among the significant covariates associated with drug exposure parameters were weight and sex for bedaquiline, alcohol use for delamanid, and weight for clofazimine.
Conclusions: We found a strong association of weight with bedaquiline and clofazimine exposure parameters, suggesting the need for weight-based dosing for those agents.