Long-Term Intake of Linezolid Elevates Drug Exposure and Reduces Drug Clearance and Elimination in Adults With Drug-Resistant Pulmonary Tuberculosis.
Journal
Therapeutic drug monitoring
ISSN: 1536-3694
Titre abrégé: Ther Drug Monit
Pays: United States
ID NLM: 7909660
Informations de publication
Date de publication:
06 Jun 2023
06 Jun 2023
Historique:
received:
11
11
2022
accepted:
16
04
2023
medline:
10
6
2023
pubmed:
10
6
2023
entrez:
9
6
2023
Statut:
aheadofprint
Résumé
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. 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. The LZD median plasma Cmax 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 (AUC0-24 = 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). 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.
Identifiants
pubmed: 37296501
doi: 10.1097/FTD.0000000000001111
pii: 00007691-990000000-00128
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
World Health Organization. Global Tuberculosis Report. Published October 2022. Accessed November 10, 2022. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022
National TB Elimination Programme. Guidelines for Programmatic Management of Drug Resistant Tuberculosis in India. Published March 2021. Accessed October 10, 2022. https://tbcindia.gov.in/showfile.php?lid=3590
Dean AS, Tosas Auguet O, Glaziou P, et al. 25 years of surveillance of drug-resistant tuberculosis: achievements, challenges, and way forward. Lancet Infect Dis. 2022;22:e191–e196.
Bahuguna A, Rawat DS. An overview of new antitubercular drugs, drug candidates, and their targets. Med Res Rev. 2020;40:263–292.
Lifan Z, Sainan B, Feng S, et al. Linezolid for the treatment of extensively drug-resistant tuberculosis: a systematic review and meta-analysis. Int J Tuberc Lung Dis. 2019;23:1293–1307.
Agyeman AA, Ofori-Asenso R. Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis. Ann Clin Microbiol Antimicrob. 2016;15:41.
Galar A, Valerio M, Muñoz P, et al. Systematic therapeutic drug monitoring for linezolid: variability and clinical impact. Antimicrob Agents Chemother. 2017;61:e00687–17.
Song T, Lee M, Jeon HS, et al. Linezolid trough concentrations correlate with mitochondrial toxicity-related adverse events in the treatment of chronic extensively drug-resistant tuberculosis. EBioMedicine. 2015;2:1627–1633.
Bolhuis MS, Tiberi S, Sotgiu G, et al. Linezolid tolerability in multidrug-resistant tuberculosis: a retrospective study. Eur Respir J. 2015;46:1205–1207.
Alffenaar JW, van Altena R, Harmelink IM, et al. Comparison of the pharmacokinetics of two dosage regimens of linezolid in multidrug-resistant and extensively drug-resistant tuberculosis patients. Clin Pharmacokinet. 2010;49:559–565.
Wasserman S, Denti P, Brust JCM, et al. Linezolid pharmacokinetics in South African patients with drug-resistant tuberculosis and a high prevalence of HIV coinfection. Antimicrob Agents Chemother. 2019;63:e02164–18.
Garcia-Prats AJ, Schaaf HS, Draper HR, et al. Pharmacokinetics, optimal dosing, and safety of linezolid in children with multidrug-resistant tuberculosis: combined data from two prospective observational studies. PLoS Med. 2019;16:e1002789.
Dietze R, Hadad DJ, McGee B, et al. Early and extended early bactericidal activity of linezolid in pulmonary tuberculosis. Am J Respir Crit Care Med. 2008;178:1180–1185.
Millard J, Pertinez H, Bonnett L, et al. Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation. J Antimicrob Chemother. 2018;73:1755–1762.
Padmapriyadarsini C, Vohra V, Bhatnagar A, et al.; for BEAT India Team. Bedaquiline, delamanid, linezolid and clofazimine for treatment of pre-extensively drug-resistant tuberculosis. Clin Infect Dis. 2022:ciac528. (In press).10.1093/cid/ciac528
doi: 10.1093/cid/ciac528
Vijayakumar A, Sudha V, Alffenaar JW, et al. A simple HPLC-UV method for therapeutic drug monitoring of Linezolid in human plasma in low-resourced settings. J Appl Bioanal. 2021;7:e21008.
Lee M, Lee J, Carroll MW, et al. Linezolid for treatment of chronic extensively drug-resistant tuberculosis. N Engl J Med. 2012;367:1508–1518.
Devaleenal Daniel B, Ramachandran G, Swaminathan S. The challenges of pharmacokinetic variability of first-line anti-TB drugs. Expert Rev Clin Pharmacol. 2017;10:47–58.
Jeyakumar SM. Micronutrient deficiency in pulmonary tuberculosis - perspective on hepatic drug metabolism and pharmacokinetic variability of first-line anti- tuberculosis drugs: special reference to fat-soluble vitamins A, D, & E and nutri-epigenetics. Drug Metab Lett. 2021;14:166–176.
da Silva Leite JM, Patriota YBG, de La Roca MF, Soares-Sobrinho JL. New perspectives in drug delivery systems for the treatment of tuberculosis. Curr Med Chem. 2022;29:1936–1958.
Dou L, Meng D, Dong Y, et al. Dosage regimen and toxicity risk assessment of linezolid in sepsis patients. Int J Infect Dis. 2020;96:105–111.
Wu F, Zhang XS, Dai Y, et al. Dosage strategy of linezolid according to the trough concentration target and renal function in Chinese critically ill patients. Front Pharmacol. 2022;13:844567.
Bandín-Vilar E, García-Quintanilla L, Castro-Balado A, et al. A review of population pharmacokinetic analyses of linezolid. Clin Pharmacokinet. 2022;61:789–817.
Rao GG, Konicki R, Cattaneo D, et al.; IATDMCT Antimicrobial Scientific Committee. Therapeutic drug monitoring can improve linezolid dosing regimens in current clinical practice: a review of linezolid pharmacokinetics and pharmacodynamics. Ther Drug Monit. 2020;42:83–92.