Long-Term Intake of Linezolid Elevates Drug Exposure and Reduces Drug Clearance and Elimination in Adults With Drug-Resistant Pulmonary Tuberculosis.
| Autor: | Jeyakumar SM; ICMR-National Institute for Research in Tuberculosis (NIRT), Chennai, India., Bhui NK; Groups of TB Hospitals (GTBH), Mumbai, India., Singla N; National Institute for Tuberculosis and Respiratory Diseases (NITRD), New Delhi, India., Vilvamani S; ICMR-National Institute for Research in Tuberculosis (NIRT), Chennai, India., Mariappan MV; ICMR-National Institute for Research in Tuberculosis (NIRT), Chennai, India., Padmapriyadarsini C; ICMR-National Institute for Research in Tuberculosis (NIRT), Chennai, India., Bhatnagar AK; Rajan Babu Institute of Pulmonary Medicine and Tuberculosis (RBIPMT), Delhi, India., Solanki R; B. J. Medical College and Hospital (BJMCH), Ahmedabad, India; and., Sridhar R; Government Hospital of Thoracic Medicine (GHTM), Chennai, India. |
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| Jazyk: | angličtina |
| Zdroj: | Therapeutic drug monitoring [Ther Drug Monit] 2023 Dec 01; Vol. 45 (6), pp. 754-759. Date of Electronic Publication: 2023 Jun 05. |
| DOI: | 10.1097/FTD.0000000000001111 |
| Abstrakt: | 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, IQR:7.36-11.35) 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. Competing Interests: The authors declare no conflict of interest. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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