scholarly journals Prospective investigations of concentration–clinical response for immunosuppressive drugs provide the scientific basis for therapeutic drug monitoring

1998 ◽  
Vol 44 (2) ◽  
pp. 381-387 ◽  
Author(s):  
Leslie M Shaw ◽  
Bruce Kaplan ◽  
Kenneth L Brayman
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Clinical Response ◽  
Drug Monitoring ◽  
Immunosuppressive Drugs ◽  
Scientific Basis ◽  
Therapeutic Drug ◽  
Controlled Clinical Trial ◽  
Target Drug ◽  
Drug Concentrations ◽  
The Individual

Abstract The performance of prospective concentration–clinical response investigations during the early stages of the development of new therapeutic agents can provide a more rigorous basis for therapeutic drug monitoring than the traditional retrospective review of drug concentrations vs clinical outcome. Here we discuss the application of the multicenter randomized concentration-controlled clinical trial study design, and related study designs, as applied to older commonly used and monitored drugs and to two new immunosuppressant drugs, mycophenolate mofetil and tacrolimus. Such studies can provide a more rigorous basis for assessing the risk/benefit associated with a target drug concentration in the individual patient and for designing future prospective pharmacokinetic and therapeutic drug monitoring investigations.

scholarly journals Pharmacokinetic considerations in geriatric cancer patients

2020 ◽  
Author(s):  
Martin Hohenegger
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Cancer Patients ◽  
Targeted Therapies ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Organ Function ◽  
Age Related ◽  
Drug Concentrations ◽  
The Individual ◽  
Age Related Changes

SummaryPharmacological anticancer therapy in elderly people has to account for pharmacokinetic aspects in view of age-related changes in organ function and disease-related alterations. Age-related changes in organ function might still be physiological and have to be discriminated from concomitant diseases and their pharmacotherapy. Although efficacy is retained with pharmacological anticancer therapies in elderly patients, plasma drug concentrations and the incidence of adverse reactions often increase. Thus, altered organ function in elderly will be reviewed with respect to clinically relevant outcomes. Furthermore, possible consequences of therapeutic drug monitoring will be discussed focusing on novel targeted therapies with small molecules. Examples of therapeutic drug monitoring during targeted therapies may represent an easy tool to overcome the individual pharmacokinetic situation of elderly cancer patients and may contribute to enhanced safety, when implemented in clinical routine.

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 Evaluation of electrochemiluminescence immunoassays for immunosuppressive drugs on the Roche cobas e411 analyzer

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1832
Author(s):  
Angela W.S. Fung ◽  
Michael J. Knauer ◽  
Ivan M. Blasutig ◽  
David A. Colantonio ◽  
Vathany Kulasingam
Keyword(s):  
Regression Analysis ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Transplant Rejection ◽  
Organ Transplant ◽  
Drug Efficacy ◽  
Immunosuppressive Drugs ◽  
Therapeutic Drug ◽  
Deming Regression ◽  
Roche Cobas

Background:  Therapeutic drug monitoring of immunosuppressant drugs are used to monitor drug efficacy and toxicity and to prevent organ transplant rejection. This study evaluates the analytical performance of semi-automated electrochemiluminescence immunoassays (ECLIA) for cyclosporine (CSA), tacrolimus (TAC) and sirolimus (SRL) on the Roche cobas e 411 analyzer at a major transplant hospital to assess method suitability and limitations. Methods: Residual whole blood samples from patients undergoing immunosuppressant therapy were used for evaluation. Imprecision, linearity, functional sensitivity, method comparisons and lot-to-lot comparisons were assessed. Results: Total imprecision ranged from 3.3 to 7.1% for CSA, 3.9 to 9.4% for TAC, and 4.6 to 8.2% for SRL. Linearity was verified from 30.0 to 960.9 μg/L for CSA, from 1.1 to 27.1 μg/L for TAC, and from 0.5 to 32.3 µg/L for SRL. The functional sensitivity met the manufacturer’s claims and was determined to be <6.5 μg/L for CSA, 1.1 μg/L for TAC, and <0.1 µg/L for SRL (CV≤20%). Deming regression analysis of method comparisons with the ARCHITECT immunoassay yielded slopes of 0.917 (95%CI: 0.885-0.949) and r of 0.985 for CSA, 0.938 (95%CI: 0.895-0.981) and r of 0.974 for TAC, and 0.842 (0.810-1.110) and r of 0.982 for SRL. Deming regression analysis of comparisons with the LC–MS/MS method yielded slopes of 1.331 (95%CI: 1.167-1.496) and r of 0.969 for CSA, 0.924 (95%CI: 0.843-1.005) and r of 0.984 for TAC, and 0.971 (95%CI: 0.913-1.030) and r of 0.993 for SRL. Conclusions: The cobas e 411 ECLIA for CSA, TAC, and SRL have acceptable precision, linearity, and functional sensitivity. The method comparisons correlated well with the ARCHITECT immunoassay and LC–MS/MS and is fit for therapeutic drug monitoring

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 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 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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