scholarly journals Ion-Channel Antiepileptic Drugs: An Analytical Perspective on the Therapeutic Drug Monitoring (TDM) of Ezogabine, Lacosamide, and Zonisamide

Analytica ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 171-194
Author(s):  
Roberto Mandrioli ◽  
Michele Protti ◽  
Lorenzo Marincich ◽  
Laura Mercolini
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Ion Channel ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Concentration Data ◽  
Analytical Perspective ◽  
Neurological Illnesses ◽  
Different Levels

The term seizures includes a wide array of different disorders with variable etiology, which currently represent one of the most important classes of neurological illnesses. As a consequence, many different antiepileptic drugs (AEDs) are currently available, exploiting different activity mechanisms and providing different levels of performance in terms of selectivity, safety, and efficacy. AEDs are currently among the psychoactive drugs most frequently involved in therapeutic drug monitoring (TDM) practices. Thus, the plasma levels of AEDs and their metabolites are monitored and correlated to administered doses, therapeutic efficacy, side effects, and toxic effects. As for any analytical endeavour, the quality of plasma concentration data is only as good as the analytical method allows. In this review, the main techniques and methods are described, suitable for the TDM of three AEDs belonging to the class of ion channel agents: ezogabine (or retigabine), lacosamide, and zonisamide. In addition to this analytical overview, data are provided, pertaining to two of the most important use cases for the TDM of antiepileptics: drug–drug interactions and neuroprotection activity studies. This review contains 146 references.

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.

Therapeutic Drug Monitoring of Antiepileptic Drugs in a Tertiary Care Hospital in India

2015 ◽  
Vol 38 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Natarajan Harivenkatesh ◽  
Natarajan Haribalaji ◽  
Darling Chellathai David ◽  
C. M. Prabu Kumar
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Therapeutic Drug ◽  
Care Hospital

scholarly journals Therapeutic Drug Monitoring of Second- and Third-Generation Antiepileptic Drugs: Insights From a College of American Pathologists Proficiency Testing Survey

2021 ◽  
Author(s):  
Matthew D. Krasowski ◽  
Thomas A. Long ◽  
Christine L. H. Snozek ◽  
Annabel Dizon ◽  
Barbarajean Magnani ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Antiepileptic Drugs ◽  
Proficiency Testing ◽  
Drug Monitoring ◽  
First Generation ◽  
Therapeutic Drug ◽  
Third Generation ◽  
Enzyme Immunoassays ◽  
Steady Growth ◽  
Survey Results

Context.— Therapeutic drug monitoring has traditionally been widely used for first-generation antiepileptic drugs (AEDs) such as carbamazepine and phenytoin. The last 2 decades have seen the introduction of second- and third-generation AEDs (eg, lamotrigine, levetiracetam, and topiramate) into clinical practice. Objective.— To use data from the College of American Pathologists Therapeutic Drug Monitoring, Extended proficiency testing survey to determine the performance of assays used for therapeutic drug monitoring of newer AEDs, including comparison of enzyme immunoassay and chromatographic techniques. Design.— Six years of proficiency testing surveys were reviewed (2013–2018). Results.— Steady growth was seen in participant volumes for newer AEDs. The analytical performance of automated enzyme immunoassays for lamotrigine, levetiracetam, and topiramate was similar to that of chromatographic methods, consistent with published literature using patient samples for comparisons. The majority of participating laboratories now use enzyme immunoassays to measure levetiracetam. Conclusions.— Survey results reflect steadily growing interest in therapeutic drug monitoring of newer AEDs. The increasing availability of robust immunoassays for new AEDs should facilitate their clinical utility, especially for clinical laboratories that do not perform chromatographic assays for therapeutic drug monitoring.

Neural and Kernal Methods for Therapeutic Drug Monitoring

2011 ◽  
pp. 238-261 ◽  
Author(s):  
G. Camps-Valls ◽  
J. D. Martin-Guerrero
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Substantial Improvement ◽  
Physical Models ◽  
Therapeutic Drug ◽  
Optimal Dosage ◽  
Blood Concentrations ◽  
Clinical Problems

Recently, important advances in dosage formulations, therapeutic drug monitoring (TDM), and the emerging role of combined therapies have resulted in a substantial improvement in patients’ quality of life. Nevertheless, the increasing amounts of collected data and the non-linear nature of the underlying pharmacokinetic processes justify the development of mathematical models capable of predicting concentrations of a given administered drug and then adjusting the optimal dosage. Physical models of drug absorption and distribution and Bayesian forecasting have been used to predict blood concentrations, but their performance is not optimal and has given rise to the appearance of neural and kernel methods that could improve it. In this chapter, we present a complete review of neural and kernel models for TDM. All presented methods are theoretically motivated, and illustrative examples in real clinical problems are included.

scholarly journals Therapeutic Drug Monitoring of Newer Antiepileptic Drugs: A Randomized Trial for Dosage Adjustment

2019 ◽  
Vol 87 (1) ◽  
pp. 22-29 ◽  
Author(s):  
Irene Aícua‐Rapún ◽  
Pascal André ◽  
Andrea O. Rossetti ◽  
Philippe Ryvlin ◽  
Andreas F. Hottinger ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Randomized Trial ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
Dosage Adjustment ◽  
Therapeutic Drug

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.

Is Therapeutic Drug Monitoring for Anti-tumour Necrosis Factor Agents in Adults With Inflammatory Bowel Disease Ready for Standard of Care? A Systematic Review and Meta-analysis

2020 ◽  
Vol 14 (8) ◽  
pp. 1057-1065 ◽  
Author(s):  
Raj Shah ◽  
Gila R Hoffman ◽  
Mohammed El-Dallal ◽  
Alexander M Goldowsky ◽  
Ye Chen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Meta Analysis ◽  
Therapeutic Drug ◽  
Quality Of Evidence ◽  
Inflammatory Bowel

Abstract Introduction Using therapeutic drug monitoring [TDM] in adult patients with inflammatory bowel disease [IBD] remains controversial. We conducted a systematic review and meta-analysis to answer four clinical PICO [Population, Intervention, Comparator, Outcome] questions. Methods We searched MEDLINE, Embase, Web of Science, and Cochrane Central from inception to June 30, 2019. Remission was defined by the manuscripts’ definitions of clinical remission. Data were analysed using RevMan 5.3. Quality of evidence was assessed with GRADE methodology. Results We identified and screened 3365 abstracts and 11 articles. PICO 1 Reactive vs No TDM: six studies pooled showed 57.1% [257/450] failed to achieve remission following reactive TDM vs 44.7% [268/600] in the no TDM group (risk ratio [RR]: 1.14; 95% confidence interval [CI] 0.88–1.47). PICO 2 Proactive vs no TDM: five studies pooled showed 19.5% [75/384] failed to maintain remission in the proactive TDM group vs 33.4% [248/742] in the no TDM group [RR: 0.60; 95% CI 0.35–1.04]. PICO 3 Proactive vs Reactive TDM: two retrospective studies pooled showed 14.2% [26/183] failure to maintain remission in the proactive TDM group and 64.7% [119/184] in the reactive TDM group [RR: 0.22; 95% CI 0.15–0.32]. PICO 4 TDM [proactive/reactive] vs No TDM: we pooled 10 studies showing 39.7% [332/837] failed to achieve remission in the TDM [proactive/reactive] cohort vs 40.3% [428/1063] in the no TDM cohort [RR: 0.94; 95% CI 0.77–1.14]. Overall, the quality of evidence in each PICO was very low when using GRADE. Conclusions This meta-analysis shows that data supporting use of TDM in adults are limited and of very low quality. Further well-designed randomized controlled trials are needed to determine the place of TDM in clinical practice.

Sign in / Sign up

Export Citation Format

Share Document