Linezolid pharmacokinetics in South African patients with drug resistant tuberculosis and a high prevalence of HIV co-infection. Wasserman, S., Denti, P., Brust, J. C M, Tareq, M., Hlungulu, S., Wiesner, L., Norman, J., Sirgel, F. A, Warren, R. M, Esmail, A., Dheda, K., Gandhi, N. R, Meintjes, G. A, & Maartens, G. Antimicrobial Agents and Chemotherapy, 63(3):e02164–18, American Society for Microbiology Journals, jan, 2019.
Linezolid pharmacokinetics in South African patients with drug resistant tuberculosis and a high prevalence of HIV co-infection. [link]Paper  doi  abstract   bibtex   
WHO recently recommended linezolid should be prioritized in treatment regimens for drug-resistant tuberculosis (TB), but there are limited data on its pharmacokinetics (PK) in this population. We conducted an observational study to explore covariate effects on linezolid PK and to estimate the probability of PK/pharmacodynamic target attainment in South African patients with drug-resistant TB. Consecutive adults on linezolid-based regimens were recruited in Cape Town and underwent intensive PK sampling at steady-state. Non-compartmental analysis was performed. Thirty participants were included: 15 HIV-positive, 26 on the initial dose of 600 mg daily and 4 participants on 300 mg daily after dose reduction for linezolid-related toxicity. There was a negative correlation between body weight and exposure with 17.4% (95% confidence interval [lsqb]CI[rsqb], 0.1 to 31.7) decrease in area under the concentration-time curve (AUC0-24) per 10 kg weight increment after adjustment for other covariates. Age was an independent predictor of trough concentration, with an estimated 43.4% (95% CI, 5.9 to 94.2) increase per 10-year increment in age. The standard 600 mg dose achieved the efficacy target of free AUC/minimum inhibitory concentration (MIC) \textgreater 119 at wild type MIC values (≤ 0.5 mg/L), but the probability of target attainment dropped to 61.5% (95% CI, 40.6 to 79.8) at the critical concentration of 1 mg/L. When dosed at 600 mg daily, trough concentrations were above the toxicity threshold of 2 mg/L in 57.7% (95% CI, 36.9 to 76.6). This confirms the narrow therapeutic index of linezolid and alternative dosing strategies should be explored.
@article{Wasserman2019,
abstract = {WHO recently recommended linezolid should be prioritized in treatment regimens for drug-resistant tuberculosis (TB), but there are limited data on its pharmacokinetics (PK) in this population. We conducted an observational study to explore covariate effects on linezolid PK and to estimate the probability of PK/pharmacodynamic target attainment in South African patients with drug-resistant TB. Consecutive adults on linezolid-based regimens were recruited in Cape Town and underwent intensive PK sampling at steady-state. Non-compartmental analysis was performed. Thirty participants were included: 15 HIV-positive, 26 on the initial dose of 600 mg daily and 4 participants on 300 mg daily after dose reduction for linezolid-related toxicity. There was a negative correlation between body weight and exposure with 17.4{\%} (95{\%} confidence interval [lsqb]CI[rsqb], 0.1 to 31.7) decrease in area under the concentration-time curve (AUC0-24) per 10 kg weight increment after adjustment for other covariates. Age was an independent predictor of trough concentration, with an estimated 43.4{\%} (95{\%} CI, 5.9 to 94.2) increase per 10-year increment in age. The standard 600 mg dose achieved the efficacy target of free AUC/minimum inhibitory concentration (MIC) {\textgreater} 119 at wild type MIC values (≤ 0.5 mg/L), but the probability of target attainment dropped to 61.5{\%} (95{\%} CI, 40.6 to 79.8) at the critical concentration of 1 mg/L. When dosed at 600 mg daily, trough concentrations were above the toxicity threshold of 2 mg/L in 57.7{\%} (95{\%} CI, 36.9 to 76.6). This confirms the narrow therapeutic index of linezolid and alternative dosing strategies should be explored.},
author = {Wasserman, Sean and Denti, Paolo and Brust, James C M and Tareq, Mahmoud and Hlungulu, Siphokazi and Wiesner, Lubbe and Norman, Jennifer and Sirgel, Frederick A and Warren, Robin M and Esmail, Aliasgar and Dheda, Keertan and Gandhi, Neel R and Meintjes, Graeme A and Maartens, Gary},
doi = {10.1128/AAC.02164-18},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wasserman et al. - 2019 - Linezolid pharmacokinetics in South African patients with drug resistant tuberculosis and a high prevalence of.pdf:pdf;:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wasserman et al. - 2019 - Linezolid pharmacokinetics in South African patients with drug resistant tuberculosis and a high prevalence(2).pdf:pdf},
journal = {Antimicrobial Agents and Chemotherapy},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {jan},
number = {3},
pages = {e02164--18},
pmid = {30617089},
publisher = {American Society for Microbiology Journals},
title = {{Linezolid pharmacokinetics in South African patients with drug resistant tuberculosis and a high prevalence of HIV co-infection.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/30617089 https://aac.asm.org/content/early/2019/01/04/AAC.02164-18},
volume = {63},
year = {2019}
}
Downloads: 0
About
Documentation
Keywords
Search
Users
Terms and Conditions of Use
Privacy Policy
Sitemap
© BibBase.org 2021