Therapeutic drug monitoring of inhaled corticosteroids in exhaled breath for adherence assessment

Reduced or absent compliance to anti-hypertensive treatment is a major obstacle to the achievement of blood pressure target in patients with arterial hypertension. Current available methods for therapeutic adherence assessment display low accuracy, limited applicability in clinical practice and/or high costs. We designed a prospective study to evaluate the accuracy of serial measurement of ARR to assess the therapeutic compliance to RAAS inhibitors. We prospectively enrolled 80 subjects: 40 patients with arterial hypertension and 40 normotensive controls. The ARR was evaluated at baseline and 2 and 8 week after initiation of a RAAS inhibitor in patients with hypertension, and at baseline and 2 weeks for the control group. Adherence to the prescribed therapy was confirmed by therapeutic drug monitoring. We observed a significant increase of renin levels and reduction of aldosterone levels after RAAS inhibitors initiation, with consequent reduction of ARR. Delta ARR (ΔARR), defined as relative change in ARR before and after treatment initiation, provided high accuracy for determination of therapeutic compliance, with an AUC of 0.900 at 2 weeks and 0.886 at 8 weeks. A cut-off of −48% of ΔARR provided 90% sensitivity and 75% specificity, at 2 and 8 weeks. In conclusion, the measurement of ΔARR is a powerful test, cheap and widely available to accurately identify the non-adherence to RAAS inhibitors treatment. Herein we propose the implementation of ΔARR in clinical practice through a multi-step flow-chart for the management of patients with uncontrolled blood pressure, with identification of those suspected of non-adherence, reserving therapeutic drug monitoring for non-adherence confirmation.

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Analysis of deferiprone in exhaled breath condensate using silver nanoparticle-enhanced terbium fluorescence

Analytical Methods ◽

10.1039/c7ay01715d ◽

2017 ◽

Vol 9 (38) ◽

pp. 5640-5645 ◽

Cited By ~ 12

Author(s):

Esmail Mohamadian ◽

Ali Shayanfar ◽

Maryam Khoubnasabjafari ◽

Vahid Jouyban-Gharamaleki ◽

Saba Ghaffary ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Silver Nanoparticle ◽

Drug Monitoring ◽

Biological Sample ◽

Exhaled Breath Condensate ◽

Therapeutic Drug ◽

Exhaled Breath ◽

Non Invasive ◽

Breath Condensate

Exhaled breath condensate (EBC) has been proposed as an alternative non-invasive biological sample for therapeutic drug monitoring.

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O21 Progress towards Therapeutic Drug Monitoring via breath analysis

Archives of Disease in Childhood ◽

10.1136/archdischild-2019-esdppp.21 ◽

2019 ◽

Vol 104 (6) ◽

pp. e9.2-e9 ◽

Cited By ~ 1

Author(s):

KD Singh ◽

V Ziesenitz ◽

J Usemann ◽

J Van Den Anker ◽

U Frey ◽

...

Keyword(s):

Data Analysis ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Breath Test ◽

Pediatric Patients ◽

Breath Analysis ◽

Therapeutic Drug ◽

Exhaled Breath ◽

Systemic Blood ◽

Blood Concentrations

BackgroundTherapeutic Drug Monitoring (TDM) is essential aspect for the clinical management of patients. However, despite the clear advantages of TDM, it faces several challenges to being more widely used in the clinic. Specially challenging is the case of TDM in children, as they experience rapid physiologic developments, leading to great pharmacokinetic and pharmacodynamic variability. Breath analysis provides a patient-friendly approach to support TDM. To explore this possibility, we are currently running a pilot study, whereby we analyze the exhaled breath of pediatric patients receiving anti-seizure or chemotherapy drugs requiring TDM.MethodsWe analyzed by secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) exhaled breath of pediatric patients under therapy for Valproic acid (VPA; n = 27), Lamotrigine (n = 19), Levetiracetam (n = 15), Oxcarbazepine (n = 11) and Methotrexate (n = 4). Systemic blood concentrations were measured simultaneously to the breath test. In the case of VPA, we constructed a regression model to predict systemic blood concentrations based on the signal intensity of breath mass spectral features. For the rest of the drugs listed, due to its current limited size, we conducted preliminary data visualization approaches.ResultsWe found that exhaled metabolites of VPA allow to predict free VPA blood concentrations with a root-mean-square error of 1.5 mg/L for concentrations in the range 0–12 mg/L. This prediction is accomplished within 20 minutes, comprising the breath test and data analysis. For Levetiracetam, Lamotrigine and Oxcarbazepine the data analysis is still ongoing. For MTX we found breath metabolites clearly altered as a result of the drug administration. However, a great inter-individual variability was also observed.ConclusionWe conclude that breath analysis may support current TDM approaches. This will lead to new opportunities to guide the dose of drugs with a high level of accuracy, in real-time and non-invasively.Disclosure(s)PS gratefully acknowledges the financial support of the Fondation Botnar (Switzerland) and the Swiss National Science Foundation (320030_173168 and PCEGP3_181300). PS is part of the board of directors of Deep Breath Initiative AG. JU was supported by research fellowship of the University Children’s Hospital Basel. VS and JVDA were supported by the Eckenstein-Geigy Foundation. *AD and PS: shared senior authorship

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Evaluation of the dose-related concentration approach in therapeutic drug monitoring of diuretics and β-blockers – drug classes with low adherence in antihypertensive therapy

Scientific Reports ◽

10.1038/s41598-019-52164-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Sabrina Ritscher ◽

Milena Hoyer ◽

Cora Wunder ◽

Nicholas Obermüller ◽

Stefan W. Toennes

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Antihypertensive Drugs ◽

Therapeutic Drug ◽

Pharmacokinetic Studies ◽

Reference Ranges ◽

Serum Samples ◽

Drug Concentrations ◽

Adherence Assessment ◽

Β Blockers

Abstract Detection of antihypertensive drugs in biological samples is an important tool to assess the adherence of hypertensive patients. Urine and serum/plasma screenings based on qualitative results may lead to misinterpretations regarding drugs with a prolonged detectability. The aim of the present study was to develop a method that can be used for therapeutic drug monitoring (TDM) of antihypertensive drugs with focus on adherence assessment. Therefore, a method for quantification of four diuretics and four β-blockers using high-performance liquid chromatography-mass spectrometric analysis (LC-MS/MS) of combined acidic and basic serum extracts was developed and validated. The method was applied to 40 serum samples from 20 patients in a supervised medication setting (trough and peak serum samples). Literature data on therapeutic concentration ranges, as well as dose-related drug concentrations (calculated from data of pharmacokinetic studies) were used to evaluate adherence assessment criteria. Concentrations were measured for bisoprolol (n = 9 patients), metoprolol (n = 7), nebivolol (n = 1), canrenone (n = 2, metabolite of spironolactone), hydrochlorothiazide (n = 10) and torasemide (n = 8). The measured concentrations were within the therapeutic reference ranges, except for 24% of the samples (mainly β-blockers). In contrast, all measured concentrations were above the lower dose-related concentration (DRC), which appears superior in evaluating adherence. In conclusion, the quantitative analysis of antihypertensive drugs in serum samples and its evaluation on the basis of the individually calculated lower DRC is a promising tool to differentially assess adherence. This method could possibly detect a lack of adherence or other causes of insufficient therapy more reliably than qualitative methods.

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Biosensor-enabled on-site therapeutic drug monitoring of antibiotics

10.21203/rs.3.rs-429808/v1 ◽

2021 ◽

Author(s):

Can Dincer ◽

Hatice Ceren Ates ◽

Hasti Mohsenin ◽

Christin Wenzel ◽

Regina Glatz ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Point Of Care ◽

Exhaled Breath Condensate ◽

Plasma Concentrations ◽

Therapeutic Drug ◽

Optimal Dosage ◽

Large Animal ◽

Exhaled Breath ◽

Drug Concentrations

Abstract Antimicrobial resistance is increasing with an alarming rate for which the prime suspect is the “one size-fits-all” dosage strategies of antibiotics. Personalized antibiotherapy framework appears as a viable option to counteract inadequate dosage, as it offers the application of the optimal dosage regimen for each individual. Such individualized scheme, however, needs frequent sampling to tailor the blood antibiotic concentration to respond unique pharmacokinetic/pharmacodynamic (PK/PD) of the patient. Herein, there are two alternative paths for feasible therapeutic drug monitoring (TDM); transforming our understanding to utilize blood based sampling within the scope of point-of-care (POC), or focusing on non-invasive samples. Here, we present a versatile biosensor along with an antibody-free assay that can be utilized in both paths for on-site TDM. The developed platform is evaluated in a large animal study (pigs exposed with overdose, normal dose, and underdose of ß lactams), in which antibiotic concentrations are quantified in matrices including whole blood, plasma, urine, saliva, and exhaled breath condensate (EBC). Herein, the detection and the clearance of drug concentrations in EBC is demonstrated for the first time. Influence of the secretion mechanisms on measured drug concentrations is then quantified by comparing the plasma concentrations with those in EBC, saliva and urine. The potential of the developed platform for blood-based POC application is further illustrated by tracking ß lactam concentrations in untreated blood samples. Finally, multiplexing capabilities are explored successfully for multianalyte/sample analysis. Enabling a rapid, low-cost, sample-independent, and multiplexed on-site TDM, this system could pave the way for the personalized drug therapies and thus, shift the paradigm of “one size-fits-all” strategies.

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Diagnose und Monitoring bei chronisch-entzündlicher Darmerkrankung

Therapeutische Umschau ◽

10.1024/0040-5930/a001002 ◽

2018 ◽

Vol 75 (5) ◽

pp. 316-328

Author(s):

Christian Ansprenger ◽

Emanuel Burri

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Morbus Crohn ◽

Therapeutic Drug ◽

Körperliche Untersuchung

Zusammenfassung. Die Diagnose und auch die Überwachung von chronisch entzündlichen Darmerkrankungen ruht auf mehreren Säulen: Anamnese, körperliche Untersuchung, Laborwerte (im Blut und Stuhl), Endoskopie, Histologie und Bildgebung. Die Diagnose kann nicht anhand eines einzelnen Befundes gestellt werden. In den letzten Jahren hat sich das Therapieziel weg von klinischen Endpunkten hin zu endoskopischen und sogar histologischen Endpunkten entwickelt. Für einige dieser neuen Therapieziele existiert allerdings noch keine allgemein gültige Definition. Regelmässige Endoskopien werden von Patienten schlecht toleriert, weshalb Surrogat-Marker wie Calprotectin untersucht wurden und eine gute Korrelation mit der mukosalen Entzündungsaktivität nachgewiesen werden konnte. Entsprechend zeigte sich bei Morbus Crohn eine Algorithmus-basierte Therapiesteuerung – unter anderem basierend auf Calprotectin – einer konventionellen Therapiesteuerung überlegen. Die Überwachung der medikamentösen Therapie («Therapeutic Drug Monitoring» [TDM]) ist ein zweites Standbein des Monitoring von chronisch entzündlichen Darmerkrankungen. Mit zunehmendem Einsatz vor allem der Biologika-Therapien wurden sowohl reaktives TDM (in Patienten mit klinischem Rezidiv) als auch proaktives TDM (in Patienten in Remission / stabiler Erkrankung) untersucht und haben (teilweise) Eingang in aktuelle Richtlinien gefunden. Zukünftige Studien werden die vorgeschlagenen Therapieziele besser definieren und den Nutzen der medikamentösen Therapieüberwachung auf den Krankheitsverlauf weiter untersuchen müssen.

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