scholarly journals Therapeutic Drug Monitoring of Linezolid: a Retrospective Monocentric Analysis

2010 ◽  
Vol 54 (11) ◽  
pp. 4605-4610 ◽  
Author(s):  
Federico Pea ◽  
Mario Furlanut ◽  
Piergiorgio Cojutti ◽  
Francesco Cristini ◽  
Eleonora Zamparini ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
High Performance ◽  
Drug Exposure ◽  
Plasma Concentrations ◽  
Hplc Method ◽  
Therapeutic Drug ◽  
Time Curve ◽  
Standard Dosage ◽  
Wide Variability

ABSTRACT The objective of the present retrospective observational study carried out in patients receiving a standard dosage of linezolid and undergoing routine therapeutic drug monitoring (TDM) was to assess the interindividual variability in plasma exposure, to identify the prevalence of attainment of optimal pharmacodynamics, and to define if an intensive program of TDM may be warranted in some categories of patients. Linezolid plasma concentrations (trough [C min] and peak [C max] levels) were analyzed by means of a high-performance liquid chromatography (HPLC) method, and daily drug exposure was estimated (daily area under the plasma concentration-time curve [AUC24]). The final database included 280 C min and 223 C max measurements performed in 92 patients who were treated with the fixed 600-mg dose every 12 h (q12h) intravenously (n = 58) or orally (n = 34). A wide variability was observed (median values [interquartile range]: 3.80 mg/liter [1.75 to 7.53 mg/liter] for C min, 14.70 mg/liter [10.57 to 19.64] for C max, and 196.08 mg·h/liter [144.02 to 312.10 mg·h/liter] for estimated AUC24). Linezolid C min was linearly correlated with estimated AUC24 (r 2 = 0.85). Optimal pharmacodynamic target attainment (defined as C min of ≥2 mg/liter and/or AUC24/MIC90 ratio of >80) was obtained in about 60 to 70% of cases, but potential overexposure (defined as C min of ≥10 mg/liter and/or AUC24 of ≥400 mg·h/liter) was documented in about 12% of cases. A significantly higher proportion of cases with potential overexposure received cotreatment with omeprazole, amiodarone, or amlodipine. Our study suggests that the application of TDM might be especially worthwhile in about 30% of cases with the intent of avoiding either the risk of dose-dependent toxicity or that of treatment failure.

scholarly journals Therapeutic Drug Monitoring of Antiepileptic Drugs in Real Clinical Practice in Russia

2018 ◽  
Vol 3 (5) ◽  
Keyword(s):  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
High Performance ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Average Dose ◽  
Observation Study ◽  
Daily Dose ◽  
Real Clinical Practice

Introduction: Anticonvulsants refer to drugs with interindividual variability of plasma concentrations and clinical efficacy. Therapeutic drug monitoring (TDM) is an important tool for optimizing pharmacotherapy with anticonvulsants in real clinical practice. The aim of the study was to analyze the results of TDM of valproates (VPA) and carbamazepine (CBZ) in epilepsy adults in clinical practice in Russia. Methods: observation study in 800 epilepsy adults (mean age 35.5±0.5) the rate of achievement the therapeutic concentrations (TC) of VPA and CBZ in different drug forms using high performance liquid chromatography; range of TC for VPA 50-150 mg/l, for CBZ 4-12 mg/l. Results: The frequency of achievement TC on VPA was 66.4% in average dose – 1325.1±29.6 mg/day with no difference between sustain-released and immediate-released drug forms. Gender differences of VPA concentrations were identified: women mean Cmin and Cmax were higher than in men with significantly lower daily dose. The frequency of sub-TC VPA was 16.3% and over-TC – 1% (Cmax 164.2±2.4mg/l); the toxic concentration for CNS (175 mg/l) was not achieved. In VPA doses<500mg/day there was no patients with TC; in 1001–1500 mg/day TC have 75%, in doses 1501–2000mg/day – 97%; in >2000 mg/day – 86% and there was high risk of over-TC (4%). The frequency of achievement TC range VPA monotherapy was 2 times more than in combination VPA+CBZ (67% versus 34%). The frequency of achievement TC range on CBZ was 78.6%, the average daily dose was 922.2±23.0 mg/day with significantly higher rate of TC range achievement when using sustain-release forms of CBZ. The frequency of sub-TC CBZ was 6.3%, over-TC – 1.25%. In patients with over-TC mean dose was 1250 mg/day, Cmin 13.5±0.2mg/l, Cmax 15.1±0.7mg/l. At initial doses<600 mg/day 64.3% patients have TC; in doses>600 mg/day – 87%. In daily doses 600-1200 mg and >1200 mg 1.3% and 4.1% patients have over-TC by both Cmin and Cmax, only by Cmax – 8.8% and 18.4%, respectively. Conclusion: the frequency of TC on VPA and CBZ is high with rare cases of over-TC, but there was problem of paradox low concentrations in single cases. CBZ have less predictable concentrations in therapeutic doses range than VPA.

scholarly journals Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6281
Author(s):  
Anna Mc Laughlin ◽  
Eduard Schmulenson ◽  
Olga Teplytska ◽  
Sebastian Zimmermann ◽  
Patrick Opitz ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Anticancer Drugs ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Plasma Concentrations ◽  
Blood Sampling ◽  
Therapeutic Drug ◽  
Study Phase ◽  
Blood Samples ◽  
Drug Concentrations

Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.

scholarly journals Development and validation of a new HPLC method for valproic acid determination in human plasma and its application to a therapeutic drug monitoring study

2020 ◽  
Vol 66 (1) ◽  
Author(s):  
Emrah Dural ◽  
Seniha Çelebi ◽  
Aslı Bolayır ◽  
Burhanettin Çiğdem
Keyword(s):  
Valproic Acid ◽  
Therapeutic Drug Monitoring ◽  
Human Plasma ◽  
Drug Monitoring ◽  
High Performance ◽  
High Standard ◽  
Hplc Method ◽  
Therapeutic Drug ◽  
Recommended Treatment ◽  
Monitoring Study

The aim of this study was to develop a new, simple and reliable high performance liquid chromatography (HPLC) method for analysis of valproic acid (VPA) in human plasma and apply to it to a therapeutic drug monitoring study. Also, the relationship between plasma-VPA concentrations and the amount of VPA used by patients was aimed to be evaluated. Plasma samples (0.25 mL) were precipitated with the same volume of acetonitrile and after centrifugation, aliquots were applied to a C18 column (250 mm x 4.6 mm). Mobile phase was prepared with phosphate buffer and acetonitrile (47.5:52.5, v/v). The flow-rate was 1.2 mL/min. Accuracy was between -2.9 and 3.2% and precision was ≤6.6%. Method was specific and sensitive with a detection limit of 2.2 µg/mL and the average recovery was 94.3%. Calibration curve was linear (r2>0.9968) from 10 to 150 µg/mL. Plasma-VPA levels of the epileptic patient population (n=33) treated with VPA between 0.5 and 1.5 g/day were also determined. Patient plasma-VPA concentrations ranged from 2.9 to 166.4 µg/g/mL (56.3±38.8). High RSD% (68.8%) was observed in dose-rated plasma-VPA results. Moreover, VPA plasma levels were found to be outside the recommended treatment range in 30.3% of the patients examined. The procedure described was found to be relatively simple, precise, and applicable for routine therapeutic drug monitoring (TDM) especially in neurology clinics or in toxicology reference laboratories. The high standard deviation (SD) observed in the dose depended plasma-VPA values of the volunteers proved the importance of TDM during the use of this drug. The results showed that for rational drug use, it is important to identify individual polymorphisms in the CYP2C9, CYP2A6 and CYP2B6 subtypes responsible for VPA metabolism, and to rearrange drug doses taking these enzyme activities into account.

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.

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