In:
Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 76, No. 4 ( 2021-03-12), p. 1019-1024
Abstract:
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 Cmin was 0.68 mg/L for bedaquiline, 0.17 mg/L for delamanid, and 0.52 mg/L for clofazimine. The median AUC0–24 was 30.6 mg·h/L for bedaquiline, 16.1 mg·h/L for clofazimine, and the AUC0–12 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.
Type of Medium:
Online Resource
ISSN:
0305-7453
,
1460-2091
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2021
detail.hit.zdb_id:
1467478-6
SSG:
15,3
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