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

2019 ◽  
Vol 9 (1) ◽  
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.

scholarly journals N22 Nurse led therapeutic drug monitoring (TDM) of Infliximab in IBD

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S667-S668
Author(s):  
S Gleeson ◽  
K Sugrue ◽  
M Buckley ◽  
J McCarthy
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Response Assessment ◽  
Symptom Improvement ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Drug Concentrations ◽  
Biologic Response ◽  
Trough Levels

Abstract Background Therapeutic drug monitoring (TDM) is the clinical practice of measuring serum drug concentrations to guide clinical decision making. Achieving therapeutic drug concentrations has been associated with clinical, endoscopic and histological outcomes in IBD. The use of TDM offers a more personalised treatment approach and is associated with sustained clinical remission. Proactive TDM was introduced to the Mercy University Hospital in 2014 for all patients on biologics. Methods One hundred patients receiving biologic infusion (Infliximab) were evaluated post induction (week 12) for therapeutic drug trough concentration and for clinical response. Serum samples were taken from all IBD patients at week 12. Biologic response assessment forms were complete for all patients to assess symptom improvement. Results Thirty-five per cent of patients had sub therapeutic trough levels at week 12. They subsequently received 3 increased doses of 10mgs/kg and levels were rechecked. Of these 90% achieved therapeutic levels after the dose escalation. 65% of patients had therapeutic levels at week 12. There was a correlation between therapeutic trough levels and patient reported improvement of clinical symptoms in 85% of respondents. Conclusion TDM in our unit facilitates appropriate dose 100 patients receiving biologic infusion (Infliximab) were evaluated post induction (week 12) for therapeutic drug trough concentration and for clinical response. Serum samples were taken from all IBD patients at week 12. Biologic response assessment forms were complete for all patients to assess symptom improvement.

scholarly journals A combined assay for quantifying remdesivir and its metabolite, along with dexamethasone, in serum

2021 ◽  
Author(s):  
Andrew Reckers ◽  
Alan H B Wu ◽  
Chui Mei Ong ◽  
Monica Gandhi ◽  
John Metcalfe ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Human Serum ◽  
Drug Monitoring ◽  
Dose Adjustment ◽  
Therapeutic Drug ◽  
Pharmacokinetic Studies ◽  
Serum Samples ◽  
Limits Of Detection ◽  
Analytical Utility

Abstract Background As global confirmed cases and deaths from coronavirus disease 2019 (COVID-19) surpass 100 and 2.2 million, respectively, quantifying the effects of the widespread treatment of remdesivir (GS-5734, Veklury) and the steroid dexamethasone is becoming increasingly important. Limited pharmacokinetic studies indicate that remdesivir concentrations in serum decrease quickly after dosing, so its primary serum metabolite GS-441524 may have more analytical utility. Objectives We developed and validated a method to quantify remdesivir, its metabolite GS-441524 and dexamethasone in human serum. Methods We used LC-MS/MS and applied the method to 23 serum samples from seven patients with severe COVID-19. Results The method has limits of detection of 0.0375 ng/mL for remdesivir, 0.375 ng/mL for GS-441524 and 3.75 ng/mL for dexamethasone. We found low intra-patient variability, but significant inter-patient variability, in remdesivir, GS-441524 and dexamethasone levels. Conclusions The significant inter-patient variability highlights the importance of therapeutic drug monitoring of COVID-19 patients and possible dose adjustment to achieve efficacy.

scholarly journals A Rapid LC–MS-MS Method for the Quantitation of Antiepileptic Drugs in Urine

2020 ◽  
Vol 44 (7) ◽  
pp. 688-696
Author(s):  
Sheng Feng ◽  
Brandi Bridgewater ◽  
Erin C Strickland ◽  
Gregory McIntire
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
Method Development ◽  
Therapeutic Drug ◽  
Reference Ranges ◽  
Concentration Data ◽  
Drug Concentrations ◽  
Repeat Rate ◽  
Analytical Range

Abstract Epilepsy is a common neurologic disease that requires treatment with one or more medications. Due to the polypharmaceutical treatments, potential side effects, and drug-drug interactions associated with these medications, therapeutic drug monitoring is important. Therapeutic drug monitoring is typically performed in blood due to established clinical ranges. While blood provides the benefit of determining clinical ranges, urine requires a less invasive collection method, which is attractive for medication monitoring. As urine does not typically have established clinical ranges, it has not become a preferred specimen for monitoring medication adherence. Thus, large urine clinical data sets are rarely published, making method development that addresses reasonable concentration ranges difficult. An initial method developed and validated in-house utilized a universal analytical range of 50–5,000 ng/mL for all antiepileptic drugs and metabolites of interest in this work, namely carbamazepine, carbamazepine-10,11-epoxide, eslicarbazepine, lamotrigine, levetiracetam, oxcarbazepine, phenytoin, 4-hydroxyphenytoin, and topiramate. This upper limit of the analytical range was too low leading to a repeat rate of 11.59% due to concentrations >5,000 ng/mL. Therefore, a new, fast liquid chromatography–tandem mass spectrometry (LC–MS-MS) method with a run time under 4 minutes was developed and validated for the simultaneous quantification of the previously mentioned nine antiepileptic drugs and their metabolites. Urine samples were prepared by solid-phase extraction and analyzed using a Phenomenex Phenyl-Hexyl column with an Agilent 6460 LC–MS-MS instrument system. During method development and validation, the analytical range was optimized for each drug to reduce repeat analysis due to concentrations above the linear range and for carryover. This reduced the average daily repeat rate for antiepileptic testing from 11.59% to 4.82%. After validation, this method was used to test and analyze patient specimens over the course of approximately one year. The resulting concentration data were curated to eliminate specimens that could indicate an individual was noncompliant with their therapy (i.e., positive for illicit drugs) and yielded between 20 and 1,700 concentration points from the patient specimens, depending on the analyte. The resulting raw quantitative urine data set is presented as preliminary reference ranges to assist with interpreting urine drug concentrations for the nine aforementioned antiepileptic medications and metabolites.

scholarly journals Rapid point-of-care anti-infliximab antibodies detection in clinical practice: comparison with ELISA and potential for improving therapeutic drug monitoring in IBD patients

2021 ◽  
Vol 14 ◽  
pp. 175628482199990
Author(s):  
Sonia Facchin ◽  
Andrea Buda ◽  
Romilda Cardin ◽  
Nada Agbariah ◽  
Fabiana Zingone ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Point Of Care ◽  
Drug Clearance ◽  
Elisa Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Inflammatory Bowel

Anti-drug antibodies can interfere with the activity of anti-tumor necrosis factor (TNF) agents by increasing drug clearance via direct neutralization. The presence of anti-drug antibodies is clinically relevant when trough drug concentrations are undetectable or sub-therapeutic. However, traditional immunoassay is not easily and rapidly accessible, making the translation of the results into treatment adjustment difficult. The availability of a point-of-care (POC) test for therapeutic drug monitoring (TDM) might represent an important step forward for improving the management of inflammatory bowel disease (IBD) patients in clinical practice. In this pilot study, we compared the results obtained with POC tests with those obtained by enzyme-linked immunosorbent assay (ELISA) in a group of IBD patients treated with Infliximab (IFX). We showed that POC test can reliably detect presence of antibody-to-IFX with 100% of specificity and 76% sensitivity, in strong agreement with the ELISA test ( k-coefficient = 0.84).

Immunosuppressant quantification in intravenous microdialysate – towards novel quasi-continuous therapeutic drug monitoring in transplanted patients

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Susanne Weber ◽  
Sara Tombelli ◽  
Ambra Giannetti ◽  
Cosimo Trono ◽  
Mark O’Connell ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Real Time ◽  
Drug Monitoring ◽  
Time Course ◽  
Drug Dosage ◽  
Immunosuppressive Drug ◽  
Therapeutic Drug ◽  
Continuous Sampling ◽  
Real Time Analysis ◽  
Drug Concentrations

AbstractObjectivesTherapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA).MethodsWe analyzed the time course over 8 h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (µD). µDs were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence detection platform. The potential of microdialysis coupled with an optical immunosensor for the TDM of immunosuppressants was assessed.ResultsUsing LC-MS/MS, the free concentrations of CsA (fCsA) and MPA (fMPA) were detectable and the time courses of total and free CsA comparable. fCsA and fMPA and area-under-the-curves (AUCs) in µDs correlated well with those determined in UCs (r≥0.79 and r≥0.88, respectively). Moreover, fCsA in µDs measured with the immunosensor correlated clearly with those determined by LC-MS/MS (r=0.82).ConclusionsThe new microdialysis-supported immunosensor allows real-time analysis of immunosuppressants and tailor-made dosing according to the AUC concept. It readily lends itself to future applications as minimally invasive and continuous near-patient TDM.

scholarly journals A Novel, Rapid, and Low-Volume Assay for Therapeutic Drug Monitoring of Posaconazole and Other Long-Chain Azole-Class Antifungal Drugs

mSphere ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Gregory R. Wiedman ◽  
Yanan Zhao ◽  
David S. Perlin
Keyword(s):  
Liquid Chromatography ◽  
Therapeutic Drug Monitoring ◽  
Human Serum ◽  
Drug Monitoring ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Human Serum Samples ◽  
Long Chain

ABSTRACT Clinicians need a better way to accurately monitor the concentration of antimicrobials in patient samples. In this report, we describe a novel, low-sample-volume method to monitor the azole-class antifungal drug posaconazole, as well as certain other long-chain azole-class antifungal drugs in human serum samples. Posaconazole represents an important target for therapeutic drug monitoring (TDM) due to its widespread use in treating invasive fungal infections and well-recognized variability of pharmacokinetics. The current “gold standard” requires trough and peak monitoring through high-pressure liquid chromatography (HPLC) or liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Other methods include bioassays that use highly susceptible strains of fungi in culture plates or 96-well formats to monitor concentrations. Currently, no method exists that is both highly accurate in detecting free drug concentrations and is also rapid. Herein, we describe a new method using reduced graphene oxide (rGO) and a fluorescently labeled aptamer, which can accurately assess clinically relevant concentrations of posaconazole and other long-chain azole-class drugs in little more than 1 h in a total volume of 100 µl. IMPORTANCE This work describes an effective assay for TDM of long-chain azole-class antifungal drugs that can be used in diluted human serum samples. This assay will provide a quick, cost-effective method for monitoring concentrations of drugs such as posaconazole that exhibit well-documented pharmacokinetic variability. Our rGO-aptamer assay has the potential to improve health care for those struggling to treat fungal infections in rural or resource-limited setting.

Pharmacokinetic Properties of New Antiepileptic Drugs

2005 ◽  
Vol 18 (6) ◽  
pp. 444-460 ◽  
Author(s):  
Michele Y. Splinter
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Interactions ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
The United States ◽  
Therapeutic Drug ◽  
Kinetic Properties ◽  
New Antiepileptic Drugs ◽  
Drug Concentrations ◽  
Pharmacokinetic Properties

Eight new antiepileptic drugs (AEDs) have been approved for use within the United States within the past decade. They are felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, and zonisamide. These afford clinicians with more options to increase efficacy and tolerability in the treatment of patients with epilepsy. Pharmacokinetic properties and drug interactions with other AEDs and other medications taken for comorbidities are individually discussed for each of these new agents. Drug concentrations are not routinely monitored for these newer agents, and there have been few studies designed to investigate their concentration-effect relationships. For most of these medications, the concentrations observed in responders and nonresponders overlap considerably and levels associated with efficacy are often associated with adverse events, complicating the definition of target ranges. Also, epilepsy manifests itself sporadically causing difficulty in clinically monitoring efficacy of medications. Therapeutic drug monitoring provides for the individualization of treatment for these agents, which is important because they demonstrate significant variability in inter- and intraindividual pharmaco-kinetic properties. Therapeutic drug monitoring also allows for identification of noncompliance, drug interactions, and toxicity. Current knowledge of the relationships between efficacy, toxicity, and drug concentrations is discussed.

scholarly journals Therapeutic drug monitoring in special populations

1998 ◽  
Vol 44 (2) ◽  
pp. 415-419 ◽  
Author(s):  
Philip D Walson
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Diagnostic Testing ◽  
Drug Effects ◽  
Special Populations ◽  
Therapeutic Drug ◽  
Drug Reactions ◽  
Drug Concentrations ◽  
Dosing Regimens ◽  
Multiple Drugs

Abstract Therapeutic drug monitoring (TDM) is commonly used to maintain “therapeutic” drug concentrations. Even in compliant patients, with “average” drug kinetics, TDM is useful to identify the causes of unwanted or unexpected responses, prevent unnecessary diagnostic testing, improve clinical outcomes, and even save lives. TDM has greatest promise in certain special populations who are: (a) prone to under- or overrespond to usual dosing regimens, (b) least able to tolerate, recognize, or communicate drug effects, or who are (c) intentionally or accidentally misdosed. TDM is especially useful in patients at the extremes of age, in adolescents, and in patients who are either taking multiple drugs or expressing unusual pharmacokinetics as a result of physiological, environmental, or genetic causes. Less-well-appreciated uses of TDM include prevention of dangerousunderdosing of patients, investigation of adverse drug reactions, and identification of serious medication errors, even for a number of drugs that are not traditionally monitored. TDM can be useful for some drugs in any patient and for most drugs in some special populations.

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