scholarly journals Suivi Thérapeutique Pharmacologique Des Antituberculeux : Quinze Ans d’Expérience

2016 ◽  
Vol 12 (21) ◽  
pp. 35
Author(s):  
Omaima El Bouazzi ◽  
Soufiane Belabbes ◽  
Latifa Ait Moussa ◽  
Rachida Soulaymani-Bencheikh ◽  
Narjis Badrane ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Therapeutic Range ◽  
Drug Monitoring ◽  
Liver Toxicity ◽  
Plasma Concentrations ◽  
Public Health Problem ◽  
Severe Side Effect ◽  
Therapeutic Drug ◽  
Poison Center ◽  
Inadequate Response

Tuberculosis is a world public health problem. Its treatment is based on a set of drugs that can cause many side effects. Liver toxicity remains one of the most common and severe side effect causing treatment failure. The objective of this study is to demonstrate the interest of therapeutic drug monitoring in the treatment of tuberculosis through the experience of the Laboratory of Toxicology and Pharmacology of the Anti Poison Center. This retrospective study involved 1152 patients who had benefited from a determination of plasma levels of first line antitubureculosis drugs (isoniasid, pyrazinamid, rifampicin) during 15 years. 135 patients had developed hepatotoxicity. The study showed that at therapeutic dose, 71.2% of TB patients had plasma concentrations lower than the therapeutic range, and 57.8% of patients had isoniazid plasma concentrations above the therapeutic range. This interindividual variability justifies the need for therapeutic drug monitoring to assess an inadequate response to tuberculosis treatment and prevent the development of hepatotoxicity.

Effect of Therapeutic Drug Monitoring and Cytochrome P450 2C19 Genotyping on Clinical Outcomes of Voriconazole: A Systematic Review

2020 ◽  
pp. 106002802094817
Author(s):  
Joseph Lee ◽  
Patrick Ng ◽  
Bassem Hamandi ◽  
Shahid Husain ◽  
Melissa J. Lefebvre ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Therapeutic Range ◽  
Drug Monitoring ◽  
Plasma Concentrations ◽  
Case Series ◽  
Therapeutic Drug ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
The Impact ◽  
Cyp2c19 Polymorphisms

Objectives To examine current knowledge on the clinical utility of therapeutic drug monitoring (TDM) in voriconazole therapy, the impact of CYP2C19 genotype on voriconazole plasma concentrations, and the role of CYP2C19 genotyping in voriconazole therapy. Data Sources Three literature searches were conducted for original reports on (1) TDM and voriconazole outcomes and (2) voriconazole and CYP2C19 polymorphisms. Searches were conducted through EMBASE, MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception to June 2020. Study Selection and Data Extraction Randomized controlled trials, cohort studies, and case series with ≥10 patients were included. Only full-text references in English were eligible. Data Synthesis A total of 63 studies were reviewed. TDM was recommended because of established concentration and efficacy/toxicity relationships. Voriconazole trough concentrations ≥1.0 mg/L were associated with treatment success; supratherapeutic concentrations were associated with increased neurotoxicity; and hepatotoxicity associations were more prevalent in Asian populations. CYP2C19 polymorphisms significantly affect voriconazole metabolism, but no relationship with efficacy/safety were found. Genotype-guided dosing with TDM was reported to increase chances of achieving therapeutic range. Relevance to Patient Care and Clinical Practice Genotype-guided dosing with TDM is a potential solution to optimizing voriconazole efficacy while avoiding treatment failures and common toxicities. Conclusions Voriconazole plasma concentrations and TDM are treatment outcome predictors, but research is needed to form a consensus target therapeutic range and dosage adjustment guidelines based on plasma concentrations. CYP2C19 polymorphisms are a predictor of voriconazole concentrations and metabolism, but clinical implications are not established. Large-scale, high-methodological-quality trials are required to investigate the role for prospective genotyping and establish CYP2C19-guided voriconazole dosing recommendations.

scholarly journals Impact on Antibiotic Resistance, Therapeutic Success, and Control of Side Effects in Therapeutic Drug Monitoring (TDM) of Daptomycin: A Scoping Review

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 263
Author(s):  
Carolina Osorio ◽  
Laura Garzón ◽  
Diego Jaimes ◽  
Edwin Silva ◽  
Rosa-Helena Bustos
Keyword(s):  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Bacterial Resistance ◽  
Plasma Concentrations ◽  
Resistant Bacteria ◽  
Therapeutic Drug ◽  
Therapeutic Success ◽  
Favorable Clinical Outcome ◽  
And Control

Antimicrobial resistance (AR) is a problem that threatens the search for adequate safe and effective antibiotic therapy against multi-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE) and Clostridium difficile, among others. Daptomycin is the treatment of choice for some infections caused by Gram-positive bacteria, indicated most of the time in patients with special clinical conditions where its high pharmacokinetic variability (PK) does not allow adequate plasma concentrations to be reached. The objective of this review is to describe the data available about the type of therapeutic drug monitoring (TDM) method used and described so far in hospitalized patients with daptomycin and to describe its impact on therapeutic success, suppression of bacterial resistance, and control of side effects. The need to create worldwide strategies for the appropriate use of antibiotics is clear, and one of these is the performance of therapeutic drug monitoring (TDM). TDM helps to achieve a dose adjustment and obtain a favorable clinical outcome for patients by measuring plasma concentrations of an administered drug, making a rational interpretation guided by a predefined concentration range, and, thus, adjusting dosages individually.

scholarly journals Software for Dosage Individualization of Voriconazole for Immunocompromised Patients

2013 ◽  
Vol 57 (4) ◽  
pp. 1888-1894 ◽  
Author(s):  
William W. Hope ◽  
Michael VanGuilder ◽  
J. Peter Donnelly ◽  
Nicole M. A. Blijlevens ◽  
Roger J. M. Brüggemann ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Fungal Infections ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Cell Transplant ◽  
Multiple Model ◽  
Pharmacokinetic Variability ◽  
Hematopoietic Stem ◽  
Wide Range

ABSTRACTThe efficacy of voriconazole is potentially compromised by considerable pharmacokinetic variability. There are increasing insights into voriconazole concentrations that are safe and effective for treatment of invasive fungal infections. Therapeutic drug monitoring is increasingly advocated. Software to aid in the individualization of dosing would be an extremely useful clinical tool. We developed software to enable the individualization of voriconazole dosing to attain predefined serum concentration targets. The process of individualized voriconazole therapy was based on concepts of Bayesian stochastic adaptive control. Multiple-model dosage design with feedback control was used to calculate dosages that achieved desired concentration targets with maximum precision. The performance of the software program was assessed using the data from 10 recipients of an allogeneic hematopoietic stem cell transplant (HSCT) receiving intravenous (i.v.) voriconazole. The program was able to model the plasma concentrations with a high level of precision, despite the wide range of concentration trajectories and interindividual pharmacokinetic variability. The voriconazole concentrations predicted after the last dosages were largely concordant with those actually measured. Simulations provided an illustration of the way in which the software can be used to adjust dosages of patients falling outside desired concentration targets. This software appears to be an extremely useful tool to further optimize voriconazole therapy and aid in therapeutic drug monitoring. Further prospective studies are now required to define the utility of the controller in daily clinical practice.

scholarly journals Quantification of 15 Antibiotics Widely Used in the Critical Care Unit with a LC-MS/MS System: An Easy Method to Perform a Daily Therapeutic Drug Monitoring

2021 ◽  
Vol 14 (12) ◽  
pp. 1214
Author(s):  
Catherine Feliu ◽  
Celine Konecki ◽  
Tristan Candau ◽  
Damien Vautier ◽  
Cyril Haudecoeur ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Plasma Concentrations ◽  
Ultra Performance Liquid Chromatography ◽  
Therapeutic Drug ◽  
Beta Lactams ◽  
Quadrupole Mass ◽  
Triple Quadrupole Mass Spectrometer ◽  
Easy Method ◽  
Routine Therapeutic Drug Monitoring

Potential under- or overdose of antibiotics may occur in intensive care units due to high variability in plasma concentrations. The risk is either treatment failure or toxicity. Thus, therapeutic drug monitoring of antibiotics may guide dosing adjustment, maximising antibacterial efficacy and minimising toxicity. The aim of this study was to develop and validate a method for the analysis of 15 antibiotics including beta-lactams, linezolid, fluoroquinolones, daptomycin, and clindamycin to have a complete panel in the management of infections. We proposed to develop a fast, sensitive, and quantitative method for the analysis of 15 antibiotics using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometer (UPLC-MS/MS) technology. this method required only 100 µL of plasma and consisted of a rapid liquid–liquid deproteinisation using methanol. Calibration curves ranged from 0.078 to 500 mg/L depending on the molecules, and were defined according to a therapeutic range. Inter- and intra-assay precisions values were less than 15%. This work described the development and the full validation of a precise, sensitive and accurate assay using UPLC-MS/MS technology. After validation, this new assay was successfully applied to routine therapeutic drug monitoring.

scholarly journals Is It Time for Systematic Voriconazole Pharmacogenomic Investigation for Central Nervous System Aspergillosis?

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
François Danion ◽  
Vincent Jullien ◽  
Claire Rouzaud ◽  
Manal Abdel Fattah ◽  
Simona Lapusan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Drug Monitoring ◽  
Invasive Aspergillosis ◽  
Drug Monitoring ◽  
Standard Treatment ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Life Threatening ◽  
Trough Plasma

ABSTRACT Voriconazole is the standard treatment for invasive aspergillosis but requires therapeutic drug monitoring to optimize therapy. We report two cases of central nervous system aspergillosis treated with voriconazole. Because of low trough plasma concentrations, we identified gain-of-function mutations in CYP2C19 that were partially responsible for the therapeutic failure of voriconazole. We suggest that systematic voriconazole pharmacogenomic investigation of cerebral aspergillosis be performed to avoid effective therapy delay in this life-threatening disease.

SPCCTDM, a Catalogue for Analysis of Therapeutic Drug Monitoring Related Contents

2013 ◽  
pp. 319-328
Author(s):  
Sven Ulrich ◽  
Pierre Baumann ◽  
Andreas Conca ◽  
Hans-Joachim Kuss ◽  
Viktoria Stieffenhofer ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Therapeutic Drug Monitoring ◽  
Text Mining ◽  
Drug Monitoring ◽  
Text Analysis ◽  
Scientific Evidence ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Drug Reactions ◽  
First Time

Therapeutic drug monitoring (TDM) has consistently been shown to be useful for optimization of drug therapy. For the first time, a method has been developed for the text analysis of TDM in SPCs in that a catalogue SPC-ContentTDM (SPCCTDM) provides a codification of the content of TDM in SPCs. It consists of six structure-related items (dose, adverse drug reactions, drug interactions, overdose, pregnancy/breast feeding, and pharmacokinetics) according to implicit or explicit references to TDM in paragraphs of the SPC, and four theory-guided items according to the information about ranges of plasma concentrations and a recommendation of TDM in the SPC. The catalogue is regarded as valid for the text analysis of SPCs with respect to TDM. It can be used in the comparison of SPCs, in the comparison with medico-scientific evidence and for the estimation of the perception of TDM in SPCs by the reader. Regarding the approach as a model of text mining, it may be extended for evaluation of other aspects reported in SPCs.

SPCCTDM, a Catalogue for Analysis of Therapeutic Drug Monitoring Related Contents in the Drug Prescription Information

2010 ◽  
Vol 1 (2) ◽  
pp. 1-11
Author(s):  
Sven Ulrich ◽  
Pierre Baumann ◽  
Andreas Conca ◽  
Hans-Joachim Kuss ◽  
Viktoria Stieffenhofer ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Text Analysis ◽  
Scientific Evidence ◽  
Drug Prescription ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Drug Reactions ◽  
First Time

Therapeutic drug monitoring (TDM) has consistently been shown to be useful for optimization of drug therapy. For the first time, a method has been developed for the text analysis of TDM in SPCs in that a catalogue SPC-ContentTDM (SPCCTDM) provides a codification of the content of TDM in SPCs. It consists of six structure-related items (dose, adverse drug reactions, drug interactions, overdose, pregnancy/breast feeding, and pharmacokinetics) according to implicit or explicit references to TDM in paragraphs of the SPC, and four theory-guided items according to the information about ranges of plasma concentrations and a recommendation of TDM in the SPC. The catalogue is regarded as valid for the text analysis of SPCs with respect to TDM. It can be used in the comparison of SPCs, in the comparison with medico-scientific evidence and for the estimation of the perception of TDM in SPCs by the reader. Regarding the approach as a model of text mining, it may be extended for evaluation of other aspects reported in SPCs.

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