scholarly journals Clinical Use and Monitoring of Antiepileptic Drugs

2018 ◽  
Vol 3 (1) ◽  
pp. 115-127 ◽  
Author(s):  
Claire E Knezevic ◽  
Mark A Marzinke
Keyword(s):  
Drug Interactions ◽  
Antiepileptic Drugs ◽  
Neurological Disorders ◽  
Genetic Factors ◽  
Patient Specific ◽  
Therapeutic Drug ◽  
Clinical Tests ◽  
Blood Concentrations ◽  
Specific Factors

Abstract Background Antiepileptic drugs (AEDs) have been used for the treatment of epilepsy and other neurological disorders since the late 19th century. There are currently several classes of AEDs available for epilepsy management, many of which are also used to treat migraines, bipolar disorder, schizophrenia, depression, and neuropathic pain. Because of their molecular and mechanistic diversity, as well as the potential for drug–drug interactions, AEDs are prescribed and monitored in a highly personalized manner. Content This review provides a general overview of the use of AEDs with a focus on the role of therapeutic drug monitoring. Discussed topics include mechanisms of action, guidelines on the clinical applications of AEDs, clinical tests available for AED monitoring, and genetic factors known to affect AED efficacy. Summary Implementation of AED therapies is highly individualized, with many patient-specific factors considered for drug and dosage selection. Both therapeutic efficacy and target blood concentrations must be established for each patient to achieve seizure mitigation or cessation. The use of an AED with any additional drug, including other AEDs, requires an evaluation of potential drug–drug interactions. Furthermore, AEDs are commonly used for nonepilepsy indications, often in off-label administration to treat neurological or psychiatric disorders.

scholarly journals A Proof of Concept of the Role of TDM-Based Clinical Pharmacological Advices in Optimizing Antimicrobial Therapy on Real-Time in Different Paediatric Settings

2021 ◽  
Vol 12 ◽  
Author(s):  
Milo Gatti ◽  
Pier Giorgio Cojutti ◽  
Caterina Campoli ◽  
Fabio Caramelli ◽  
Luigi Tommaso Corvaglia ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Real Time ◽  
Antimicrobial Therapy ◽  
Turnaround Time ◽  
Antimicrobial Treatment ◽  
Therapeutic Drug ◽  
Proof Of Concept ◽  
Paediatric Patients ◽  
Dosing Regimens

Introduction: Antimicrobial treatment is quite common among hospitalized children. The dynamic age-associated physiological variations coupled with the pathophysiological alterations caused by underlying illness and potential drug-drug interactions makes the implementation of appropriate antimicrobial dosing extremely challenging among paediatrics. Therapeutic drug monitoring (TDM) may represent a valuable tool for assisting clinicians in optimizing antimicrobial exposure. Clinical pharmacological advice (CPA) is an approach based on the correct interpretation of the TDM result by the MD Clinical Pharmacologist in relation to specific underlying conditions, namely the antimicrobial susceptibility of the clinical isolate, the site of infection, the pathophysiological characteristics of the patient and/or the drug-drug interactions of cotreatments. The aim of this study was to assess the role of TDM-based CPAs in providing useful recommendations for the real-time personalization of antimicrobial dosing regimens in various paediatric settings.Materials and methods: Paediatric patients who were admitted to different settings of the IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy (paediatric intensive care unit [ICU], paediatric onco-haematology, neonatology, and emergency paediatric ward), between January 2021 and June 2021 and who received TDM-based CPAs on real-time for personalization of antimicrobial therapy were retrospectively assessed. Demographic and clinical features, CPAs delivered in relation to different settings and antimicrobials, and type of dosing adjustments were extracted. Two indicators of performance were identified. The number of dosing adjustments provided over the total number of delivered CPAs. The turnaround time (TAT) of CPAs according to a predefined scale (optimal, <12 h; quasi-optimal, between 12–24 h; acceptable, between 24–48 h; suboptimal, >48 h).Results: Overall, 247 CPAs were delivered to 53 paediatric patients (mean 4.7 ± 3.7 CPAs/patient). Most were delivered to onco-haematological patients (39.6%) and to ICU patients (35.8%), and concerned mainly isavuconazole (19.0%) and voriconazole (17.8%). Overall, CPAs suggested dosing adjustments in 37.7% of cases (24.3% increases and 13.4% decreases). Median TAT was 7.5 h (IQR 6.1–8.8 h). Overall, CPAs TAT was optimal in 91.5% of cases, and suboptimal in only 0.8% of cases.Discussion: Our study provides a proof of concept of the helpful role that TDM-based real-time CPAs may have in optimizing antimicrobial exposure in different challenging paediatric scenarios.

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.

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 2112. Voriconazole for Primary Prophylaxis: A Decade of Trends and Outcomes

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S715-S715
Author(s):  
Ahmad Mourad ◽  
Melissa D Johnson ◽  
John R Perfect
Keyword(s):  
Drug Interactions ◽  
Fungal Infections ◽  
Primary Prophylaxis ◽  
Antifungal Prophylaxis ◽  
University Hospital ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Blood Concentrations ◽  
The Mean ◽  
Microbiological Data

Abstract Background Invasive fungal infections (IFI) continue to affect the immunocompromised patient population. Many of these patients require antifungal prophylaxis. Voriconazole is an azole antifungal that has been utilized for preventing IFIs but does not have an approved indication for prophylaxis. Methods Adult patients admitted to Duke University Hospital from January 1, 2005 to December 31, 2015 who had received at least 2 days of systemic voriconazole as primary prophylaxis were included in this retrospective medical records review. Demographics, underlying comorbidities, adverse events, drug interactions, voriconazole blood concentrations, and microbiological data were assessed. Results Our review identified 403 patients receiving voriconazole for primary prophylaxis. 220 (55.6%) were male, 303 (75.2%) were Caucasian, and the mean age was 46.0 ± 15.7 years. 233 (57.8%) had leukemia, and 63 (15.6%) had lymphoma. 301 (74.7%) underwent hematopoietic transplant (BMT), and 45 (11.2%) had a solid-organ transplant. 176 (43.7%) patients received chemotherapy and 261 (64.8%) received immunosuppressive drugs. The mean voriconazole total daily maintenance dose was 416.1 ± 65.9 mg (5.5 ± 1.6 mg/kg/day). Patients received inpatient voriconazole for a mean of 19.5 ± 16.5 days. 371 (92.1%) patients received a concomitant interacting drug. Only 140 (43.7%) patients had therapeutic drug monitoring. The mean first voriconazole serum concentration was 1.8 ± 1.7 mg/L. 87 (21.6%) patients discontinued voriconazole prematurely; 41 (10.2% overall) of these patients had an adverse event requiring discontinuation. 5 had breakthrough fungal infections with microbiological data identifying a fungal species, which included Rhizopus spp. among others. Conclusion Voriconazole is frequently used for primary prophylaxis of IFIs and most commonly in BMT. It appears to be relatively well tolerated with some adverse side-effects (~10%) despite many potential drug–drug interactions and provides appropriate fungal coverage for many immunosuppressed patients. However, few patients had breakthrough fungal infections while receiving voriconazole. In a real-world setting, voriconazole can provide antifungal prevention in certain high-risk patients. Disclosures All authors: No reported disclosures.

scholarly journals P91 Real-time breath analysis of antiepileptic drugs

2019 ◽  
Vol 104 (6) ◽  
pp. e55.1-e55
Author(s):  
KD Singh ◽  
V Ziesenitz ◽  
J Usemann ◽  
U Frey ◽  
J van den Anker ◽  
...  
Keyword(s):  
Antiepileptic Drugs ◽  
Mass Spectra ◽  
High Resolution Mass Spectrometry ◽  
Exhaled Breath Condensate ◽  
Personalised Medicine ◽  
Therapeutic Window ◽  
Therapeutic Drug ◽  
Exhaled Breath ◽  
Blood Concentrations ◽  
Data Analyses

BackgroundIn the field of medicine, serum concentrations of drugs with a narrow therapeutic window, used to treat seizures, are measured to assure the most efficacious and safe way of treating every individual patient. This form of personalised medicine is called therapeutic drug monitoring (TDM). We have explored the possibility to measure and monitor drugs in exhaled breath (EB), to perform completely painless and non-invasive TDM for a future clinical application especially in pediatric patients.MethodsWe employed secondary electrospray ionisation in combination with high resolution mass spectrometry to obtain highly resolved EB mass spectra. We then statistically compared these EB mass spectra between patients taking antiepileptic drugs against controls (no drugs), to find potential EB-based bio-markers for drugs. Suspected drug metabolites detected in breath will be compared with systemic blood concentrations. We will screen a total of 15 drugs requiring TDM.ResultsSo far we have successfully measured EB mass spectra of patients undergoing treatment with Valproic acid (VPA, n = 27), Lamotrigine (n = 19), Levetiracetam (n = 15) and Oxcarbazepine (n = 11). Exploratory data analyses are still ongoing for these drugs. However, for VPA we have identified few candidate ions which enables us to predict free VPA blood concentrations (RMSE 1.5 mg/L). Additionally, we have positively identify two molecules involved in free VPA prediction, based on LC-MS/MS of the exhaled breath condensate. In the near future we will continue to perform data analyses and LC-MS/MS on ions of interest to confirm their identity.ConclusionsThis work is a part of an ongoing study and it is too early to come up with a definite conclusion. However, we observed several differentially abundant ions between controls and epileptic patients for various drugs, but the identity and clinical significance of these ions is yet to be determined.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. VZ and JV are supported by the Eckenstein-Geigy Foundation. *AD and PS: shared senior authorship.

scholarly journals Modeling Neurodevelopmental and Neuropsychiatric Diseases with Astrocytes Derived from Human-Induced Pluripotent Stem Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1692
Author(s):  
Baiyan Ren ◽  
Anna Dunaevsky
Keyword(s):  
Stem Cell ◽  
Neurological Disorders ◽  
Stem Cell Differentiation ◽  
Patient Specific ◽  
Human Astrocytes ◽  
Structural And Functional Properties ◽  
Neuropsychiatric Diseases ◽  
The Central Nervous System ◽  
Induced Pluripotent

Accumulating studies demonstrate the morphological and functional diversity of astrocytes, a subtype of glial cells in the central nervous system. Animal models are instrumental in advancing our understanding of the role of astrocytes in brain development and their contribution to neurological disease; however, substantial interspecies differences exist between rodent and human astrocytes, underscoring the importance of studying human astrocytes. Human pluripotent stem cell differentiation approaches allow the study of patient-specific astrocytes in the etiology of neurological disorders. In this review, we summarize the structural and functional properties of astrocytes, including the unique features of human astrocytes; demonstrate the necessity of the stem cell platform; and discuss how this platform has been applied to the research of neurodevelopmental and neuropsychiatric diseases.

Therapeutic, Toxic and Fatal Blood Concentration Ranges of Antiepileptic Drugs as an Aid to the Interpretation of Analytical Data

1983 ◽  
Vol 2 (1) ◽  
pp. 135-147 ◽  
Author(s):  
A.H. Stead ◽  
W. Hook ◽  
A.C. Moffat ◽  
D. Berry
Keyword(s):  
Antiepileptic Drugs ◽  
Analytical Data ◽  
Forensic Toxicology ◽  
Therapeutic Drug ◽  
Response Curves ◽  
Blood Concentrations ◽  
Reference Information ◽  
Drug Concentrations ◽  
Available Information ◽  
Numerical Representations

1 Problems associated with the interpretation of analytical results are often related to the ineffective presentation of reference information. Concentration-response curves overcome many of the problems by presenting all available information concisely and by allowing clear comparisons between drug concentrations associated with different pharmacological responses. Although visual comparison of such curves is possible, it can be advantageous to represent them numerically. 2 Numerical representations are used in the present work to compare sub-therapeutic, optimally therapeutic, toxic (side-effects and severe effects), and fatal blood concentrations of the commonly prescribed antiepileptic drugs. 3 Blood drug concentrations accounting for 50% of the population (EC50) are expressed in relation to the concentrations accounting for 10% (EC10) and 90% (EC 90) of the population in each clinical category. 4 Such EC10 -EC50-EC90 ranges are shown to represent adequately the concentration-response curves. They demonstrate the overlap between drug blood concentrations associated with the various responses and give a good indication of the expected response at any concentration. The concentration ranges are therefore a very useful interpretative aid in therapeutic drug monitoring, emergency toxicology, and forensic toxicology.

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