Pharmacokinetic considerations in geriatric cancer patients

memo - Magazine of European Medical Oncology ◽

10.1007/s12254-020-00668-z ◽

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.

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

Clinical Chemistry ◽

10.1093/clinchem/44.2.381 ◽

1998 ◽

Vol 44 (2) ◽

pp. 381-387 ◽

Cited By ~ 1

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.

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

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284821999902 ◽

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).

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

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-1542 ◽

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.

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Pharmacokinetic Properties of New Antiepileptic Drugs

Journal of Pharmacy Practice ◽

10.1177/0897190005282733 ◽

2005 ◽

Vol 18 (6) ◽

pp. 444-460 ◽

Cited By ~ 8

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.

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

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.1005 ◽

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.

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Therapeutic drug monitoring in special populations

Clinical Chemistry ◽

10.1093/clinchem/44.2.415 ◽

1998 ◽

Vol 44 (2) ◽

pp. 415-419 ◽

Cited By ~ 20

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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Population Pharmacokinetics of Gentamicin and Dosing Optimization for Infants

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03464-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 482-489 ◽

Cited By ~ 13

Author(s):

Susanna E. Medellín-Garibay ◽

Aída Rueda-Naharro ◽

Silvia Peña-Cabia ◽

Benito García ◽

Silvia Romano-Moreno ◽

...

Keyword(s):

Body Weight ◽

Therapeutic Drug Monitoring ◽

Population Pharmacokinetics ◽

Drug Monitoring ◽

Pediatric Population ◽

External Validation ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Time Data ◽

Age Related

ABSTRACTThe aim of this study was to characterize and validate the population pharmacokinetics of gentamicin in infants and to determine the influences of clinically relevant covariates to explain the inter- and intraindividual variabilities associated with this drug. Infants receiving intravenous gentamicin and with routine therapeutic drug monitoring were consecutively enrolled in the study. Plasma concentration and time data were retrospectively collected from 208 infants (1 to 24 months old) of the Hospital Universitario Severo Ochoa (Spain), of whom 44% were males (mean age [± standard deviation], 5.8 ± 4.8 months; mean body weight, 6.4 ± 2.2 kg). Data analysis was performed with NONMEM 7.2. One- and two-compartment open models were analyzed to estimate the gentamicin population parameters and the influences of several covariates. External validation was carried out in another population of 55 infants. The behavior of gentamicin in infants exhibits two-compartment pharmacokinetics, with total body weight being the covariate that mainly influences central volume (Vc) and clearance (CL); this parameter was also related to creatinine clearance. Both parameters are age related and different from those reported for neonatal populations. On the basis of clinical presentation and diagnosis, a once-daily dosage regimen of 7 mg/kg of body weight every 24 h is proposed for intravenous gentamicin, followed by therapeutic drug monitoring in order to avoid toxicity and ensure efficacy with minimal blood sampling. Gentamicin pharmacokinetics and disposition were accurately characterized in this pediatric population (infants), with the parameters obtained being different from those reported for neonates and children. These differences should be considered in the dosing and therapeutic monitoring of this antibiotic.

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