scholarly journals Treatment of multidrug-resistant tuberculosis using therapeutic drug monitoring: first experiences with sub-300 mg linezolid dosages using in-house made capsules

2019 ◽  
Vol 54 (6) ◽  
pp. 1900580 ◽  
Author(s):  
Mathieu S. Bolhuis ◽  
Tjip S. van der Werf ◽  
Huib A.M. Kerstjens ◽  
Wiel C.M. de Lange ◽  
Jan-Willem C. Alffenaar ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Multidrug Resistant ◽  
Therapeutic Drug ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

scholarly journals Individualized treatment of multidrug-resistant tuberculosis using therapeutic drug monitoring

2016 ◽  
Vol 5 ◽  
pp. S44-S45 ◽  
Author(s):  
Mathieu S. Bolhuis ◽  
Onno W. Akkerman ◽  
Marieke G.G. Sturkenboom ◽  
Wiel C.M. de Lange ◽  
Tjip S. van der Werf ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Multidrug Resistant ◽  
Individualized Treatment ◽  
Therapeutic Drug ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

scholarly journals Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Linezolid in Patients with Multidrug-Resistant Tuberculosis

2012 ◽  
Vol 56 (11) ◽  
pp. 5758-5763 ◽  
Author(s):  
D. H. Vu ◽  
M. S. Bolhuis ◽  
R. A. Koster ◽  
B. Greijdanus ◽  
W. C. M. de Lange ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Multidrug Resistant ◽  
Dried Blood Spot ◽  
Therapeutic Drug ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Blood Spot

ABSTRACTLinezolid is a promising antimicrobial agent for the treatment of multidrug-resistant tuberculosis (MDR-TB), but its use is limited by toxicity. Therapeutic drug monitoring (TDM) may help to minimize toxicity while adequate drug exposure is maintained. Conventional plasma sampling and monitoring might be hindered in many parts of the world by logistical problems that may be solved by dried blood spot (DBS) sampling. The aim of this study was to develop and validate a novel method for TDM of linezolid in MDR-TB patients using DBS sampling. Plasma, venous DBS, and capillary DBS specimens were obtained simultaneously from eight patients receiving linezolid. A DBS sampling method was developed and clinically validated by comparing DBS with plasma results using Passing-Bablok regression and Bland-Altman analysis. This study showed that DBS analysis was reproducible and robust. Accuracy and between- and within-day precision values from three validations presented as bias and coefficient of variation (CV) were less than 17.2% for the lower limit of quantification and less than 7.8% for other levels. The method showed a high recovery of approximately 95% and a low matrix effect of less than 8.7%. DBS specimens were stable at 37°C for 2 months and at 50°C for 1 week. The ratio of the concentration of linezolid in DBS samples to that in plasma was 1.2 (95% confidence interval [CI], 1.12 to 1.27). Linezolid exposure calculated from concentrations DBS samples and plasma showed good agreement. In conclusion, DBS analysis of linezolid is a promising tool to optimize linezolid treatment in MDR-TB patients. An easy sampling procedure and high sample stability may facilitate TDM, even in underdeveloped countries with limited resources and where conventional plasma sampling is not feasible.

scholarly journals Clinical Validation of the Analysis of Linezolid and Clarithromycin in Oral Fluid of Patients with Multidrug-Resistant Tuberculosis

2013 ◽  
Vol 57 (8) ◽  
pp. 3676-3680 ◽  
Author(s):  
M. S. Bolhuis ◽  
R. van Altena ◽  
K. van Hateren ◽  
W. C. M. de Lange ◽  
B. Greijdanus ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Correction Factor ◽  
Drug Monitoring ◽  
Oral Fluid ◽  
Multidrug Resistant ◽  
Therapeutic Drug ◽  
Specific Patient ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

ABSTRACTLinezolid plays an increasingly important role in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, patients should be carefully monitored due to time- and dose-dependent toxicity. Clarithromycin plays a more modest role. Therapeutic drug monitoring may contribute to assessment of treatment regimens, helping to reduce toxicity while maintaining adequate drug exposure. Oral fluid sampling could provide a welcome alternative in cases where conventional plasma sampling is not possible or desirable. The aim of this study was to clinically validate the analysis of linezolid and clarithromycin and its metabolite hydroxyclarithromycin in oral fluid of patients with multidrug-resistant tuberculosis. Serum and oral fluid samples were simultaneously obtained and analyzed by using validated methods, after extensive cross-validation between the two matrices. Passing-Bablok regressions and Bland-Altman analysis showed that oral fluid analysis of linezolid and clarithromycin appeared to be suitable for therapeutic drug monitoring in MDR-TB patients. No correction factor is needed for the interpretation of linezolid oral fluid concentrations with a ratio of the linezolid concentration in serum to that in oral fluid of 0.97 (95% confidence interval [CI], 0.92 to 1.02). However, the clarithromycin concentration serum/clarithromycin concentration in oral fluid ratio is 3.07 (95% CI, 2.45 to 3.69). Analysis of hydroxyclarithromycin in oral fluid was not possible in this study due to a nonlinear relationship between the concentration in serum and that in oral fluid. In conclusion, the analysis of linezolid (no correction factor) and clarithromycin (correction factor of 3) in oral fluid is applicable for therapeutic drug monitoring in cases of multidrug-resistant tuberculosis as an alternative to conventional serum sampling. Easy sampling using a noninvasive technique may facilitate therapeutic drug monitoring for specific patient categories.

Limited Sampling Strategies for Therapeutic Drug Monitoring of Linezolid in Patients With Multidrug-Resistant Tuberculosis

2010 ◽  
Vol 32 (1) ◽  
pp. 97-101 ◽  
Author(s):  
Jan-Willem C Alffenaar ◽  
Jos G W Kosterink ◽  
Richard van Altena ◽  
Tjip S van der Werf ◽  
Donald R A Uges ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Multidrug Resistant ◽  
Therapeutic Drug ◽  
Sampling Strategies ◽  
Resistant Tuberculosis ◽  
Limited Sampling ◽  
Multidrug Resistant Tuberculosis

scholarly journals Evaluation of Saliva as a Potential Alternative Sampling Matrix for Therapeutic Drug Monitoring of Levofloxacin in Patients with Multidrug-Resistant Tuberculosis

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Samiksha Ghimire ◽  
Bhagwan Maharjan ◽  
Erwin M. Jongedijk ◽  
Jos G. W. Kosterink ◽  
Gokarna R. Ghimire ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Multidrug Resistant ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Time Curve ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Liquid Chromatography Tandem Mass ◽  
Mdr Tb

ABSTRACT Saliva may be a useful alternative matrix for monitoring levofloxacin concentrations in multidrug-resistant tuberculosis (MDR-TB) patients. The objectives of this study were (i) to evaluate the correlation between plasma and salivary levofloxacin (Lfx) concentrations in MDR-TB patients and (ii) to gauge the possibility of using saliva as an alternative sampling matrix for therapeutic drug monitoring of Lfx in areas where TB is endemic. This was a prospective pharmacokinetic study that enrolled MDR-TB patients receiving levofloxacin (750- to 1,000-mg once-daily dosing) under standardized treatment regimen in Nepal. Paired blood and saliva samples were collected at steady state. Lfx concentrations were quantified using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated using noncompartmental kinetics. Lfx drug exposures were evaluated in 23 MDR-TB patients. During the first month, the median (interquartile range [IQR]) areas under the concentration-time curve from 0 to 24 h (AUC0–24) were 67.09 (53.93 to 98.37) mg ⋅ h/liter in saliva and 99.91 (76.80 to 129.70) mg ⋅ h/liter in plasma, and the saliva plasma (S/P) ratio was 0.69 (0.53 to 0.99). Similarly, during the second month, the median (IQR) AUC0–24 were 75.63 (61.45 to 125.5) mg ⋅ h/liter in saliva and 102.7 (84.46 to 131.9) mg ⋅ h/liter in plasma, with an S/P ratio of 0.73 (0.66 to 1.18). Furthermore, large inter- and intraindividual variabilities in Lfx concentrations were observed. This study could not demonstrate a strong correlation between plasma and saliva Lfx levels. Despite a good Lfx penetration in saliva, the variability in individual saliva-to-plasma ratios limits the use of saliva as a valid substitute for plasma. Nevertheless, saliva could be useful in semiquantitatively predicting Lfx plasma levels. (This study has been registered at ClinicalTrials.gov under identifier NCT03000517.)

Use of Therapeutic Drug Monitoring for Multidrug-Resistant Tuberculosis Patients

CHEST Journal ◽  
2004 ◽  
Vol 126 (6) ◽  
pp. 1770-1776 ◽  
Author(s):  
Jiehui Li ◽  
Joseph N. Burzynski ◽  
Yi-An Lee ◽  
Debra Berg ◽  
Cynthia R. Driver ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Multidrug Resistant ◽  
Therapeutic Drug ◽  
Tuberculosis Patients ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis
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