scholarly journals Population pharmacokinetics and target attainment analysis of linezolid in multidrug‐resistant tuberculosis patients

2021 ◽  
Author(s):  
Anna K. Tietjen ◽  
Niklas Kroemer ◽  
Dario Cattaneo ◽  
Sara Baldelli ◽  
Sebastian G. Wicha
Keyword(s):  
Population Pharmacokinetics ◽  
Multidrug Resistant ◽  
Target Attainment ◽  
Tuberculosis Patients ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

The effect of isoniazid intake on ethionamide pharmacokinetics and target attainment in multidrug-resistant tuberculosis patients.

2021 ◽  
Author(s):  
Maxwell T. Chirehwa ◽  
Richard Court ◽  
Mariana de Kock ◽  
Lubbe Wiesner ◽  
Nihal de Vries ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Fat Free Mass ◽  
Hepatic Extraction ◽  
Target Attainment ◽  
Post Dose ◽  
Tuberculosis Patients ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Disposition Model

Ethionamide is recommended as part of regimens to treat multidrug-resistant and rifampicin-resistant tuberculosis. The study was conducted to (i) describe the distribution of ethionamide minimum inhibitory concentrations (MICs), (ii) describe the pharmacokinetics of ethionamide, and (iii) determine the probability of attaining target AUC 0-24 /MIC values associated with suppression of resistant subpopulation and microbial kill. Participants received 15–20 mg/kg of ethionamide daily (in 500 or 750 mg doses), as part of a multidrug regimen. Pretreatment MICs of ethionamide for M. tuberculosis sputum isolates were determined using Sensititre MYCOTB MIC plates. Plasma concentrations of ethionamide (measured pre-dose and at 2, 4, 6, 8 and 10 hours post-dose) were available for 84 patients. A one-compartment disposition model including a liver compartment capturing hepatic extraction, best described ethionamide pharmacokinetics. Clearance and volume were allometrically scaled using fat-free mass. Isoniazid co-administration reduced ethionamide clearance by 31% resulting in a 44% increase in AUC 0-24 . The median (range) MIC (n=111) was 2.5 mg/L (<0.3 to >40 mg/L). Simulations showed increased daily doses of ethionamide (1 250 mg, 1 500 mg, and 1 750 mg for patients weighing ≤45 kg, 46-70 kg, and >70 kg, respectively) resulted in the probability of attaining a f AUC 0-24 /MIC ratio ≥ 42 in more than 90% of patients, only at the lowest MIC of 0.3 mg/L. The WHO recommended doses of ethionamide do not achieve target concentrations even for the lowest MIC measured in the cohort.

scholarly journals Population Pharmacokinetics and Pharmacodynamics of Ofloxacin in South African Patients with Multidrug-Resistant Tuberculosis

2012 ◽  
Vol 56 (7) ◽  
pp. 3857-3863 ◽  
Author(s):  
Emmanuel Chigutsa ◽  
Sandra Meredith ◽  
Lubbe Wiesner ◽  
Nesri Padayatchi ◽  
Joe Harding ◽  
...  
Keyword(s):  
South Africa ◽  
Population Pharmacokinetics ◽  
South African ◽  
Multidrug Resistant ◽  
Pharmacokinetic Data ◽  
Target Attainment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Study Population ◽  
African Patients

ABSTRACTDespite the important role of fluoroquinolones and the predominant use of ofloxacin for treating multidrug-resistant tuberculosis in South Africa, there are limited data on ofloxacin pharmacokinetics in patients with multidrug-resistant tuberculosis, no ofloxacin pharmacokinetic data from South African patients, and no direct assessment of the relationship between ofloxacin pharmacokinetics and the MIC of ofloxacin of patient isolates. Our objectives are to describe ofloxacin pharmacokinetics in South African patients being treated for multidrug-resistant tuberculosis and assess the adequacy of ofloxacin drug exposure with respect to the probability of pharmacodynamic target attainment (area under the time curve/MIC ratio of at least 100). Sixty-five patients with multidrug-resistant tuberculosis were recruited from 2 hospitals in South Africa. We determined the ofloxacin MICs for theMycobacterium tuberculosisisolates from baseline sputum specimens. Patients received daily doses of 800 mg ofloxacin, in addition to other antitubercular drugs. Patients underwent pharmacokinetic sampling at steady state. NONMEM was used for data analysis. The population pharmacokinetics of ofloxacin in this study has been adequately described. The probability of target attainment expectation in the study population was 0.45. Doubling the dose to 1,600 mg could increase this to only 0.77. The currently recommended ofloxacin dose appeared inadequate for the majority of this study population. Studies to assess the tolerability of higher doses are warranted. Alternatively, ofloxacin should be replaced with more potent fluoroquinolones.

Biobank for multidrug-resistant tuberculosis research: Importance of sequential samples

2021 ◽  
Author(s):  
Yoohyun Hwang ◽  
Jiyeon Kim ◽  
Seungkyu Park ◽  
Sungweon Ryoo
Keyword(s):  
International Research ◽  
Multidrug Resistant ◽  
Tuberculosis Patients ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
National Tuberculosis ◽  
Sequential Samples ◽  
Resistant Strains

Abstract Since 2013, Masan National Tuberculosis Hospital has collected standardized specimens from its tuberculosis patients, which include a large number of multidrug-resistant strains. The repository collects matched participants and their bacilli samples, compiling sequential samples from the beginning of treatment. The repository aims to provide resources for in-depth international research.

scholarly journals Aminoglycoside-induced hearing loss in HIV-positive and HIV-negative multidrug-resistant tuberculosis patients

2012 ◽  
Vol 102 (6) ◽  
pp. 363 ◽  
Author(s):  
Tashneem Harris ◽  
Soraya Bardien ◽  
H Simon Schaaf ◽  
Lucretia Petersen ◽  
Greetje De Jong ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Multidrug Resistant ◽  
Hiv Positive ◽  
Tuberculosis Patients ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Hiv Negative
Sign in / Sign up

Export Citation Format

Share Document