Long-Term Intake of Linezolid Elevates Drug Exposure and Reduces Drug Clearance and Elimination in Adults With Drug-Resistant Pulmonary Tuberculosis.
Ther Drug Monit
; 45(6): 754-759, 2023 12 01.
Article
en En
| MEDLINE
| ID: mdl-37296501
ABSTRACT
PURPOSE:
Pharmacokinetic (PK) studies are critical for dose optimization, and there is a paucity of linezolid (LZD) PK data for prolonged use in drug-resistant tuberculosis (DR-TB). Therefore, the authors evaluated the pharmacokinetics of LZD at two-time intervals in DR-TB during long-term use.METHODS:
PK evaluation of LZD was performed at the end of the 8th and 16th weeks of treatment in a randomly selected subset of adult pre-extensively drug-resistant pulmonary tuberculosis patients (n = 18) from a multicentric interventional study (Building Evidence to Advance Treatment of TB/BEAT study; CTRI/2019/01/017310), wherein a daily dose of 600 mg LZD was used for 24 weeks. Plasma LZD levels were measured using a validated high-pressure liquid chromatography (HPLC) method.RESULTS:
The LZD median plasma C max was comparable between the 8th and 16th weeks [18.3 mg/L, interquartile range (IQR 15.5-20.8 and 18.8 mg/L, IQR 16.0-22.7, respectively)]. However, the trough concentration increased significantly in the 16th week (3.16 mg/L, IQR 2.30-4.76), compared with the 8th week (1.98 mg/L, IQR 0.93-2.75). Furthermore, compared with the 8th week, in the 16th week, there was a significant increase in drug exposure (AUC 0-24 = 184.2 mg*h/L, IQR 156.4-215.8 versus 233.2 mg*h/L, IQR 187.9-277.2), which corroborated with a longer elimination half-life (6.94 hours, IQR 5.55-7.99 versus 8.47 hours, IQR7.36-11.35) and decreased clearance (2.91 L/h, IQR 2.45-3.33 versus 2.19 L/h, IQR 1.49-2.78).CONCLUSIONS:
Long-term daily intake of 600 mg LZD resulted in a significant elevation in trough concentration (>2.0 mg/L) in 83% of the study participants. Furthermore, increased LZD drug exposure may be partly because of decreased clearance and elimination. Overall, the PK data underscore the need for dose adjustment when LZDs are intended for long-term treatment.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tuberculosis Pulmonar
/
Tuberculosis Resistente a Múltiples Medicamentos
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Humans
Idioma:
En
Revista:
Ther Drug Monit
Año:
2023
Tipo del documento:
Article
País de afiliación:
India