Dried Blood Microsampling-Based Therapeutic Drug Monitoring of Antiepileptic Drugs in Children With Nodding Syndrome and Epilepsy in Uganda and the Democratic Republic of the Congo
Abstract:
Nodding syndrome is a highly debilitating, generalized seizure disorder, affecting children in subregions of sub-Saharan Africa. Despite numerous efforts to uncover the etiology, the exact cause of this syndrome still remains obscure. Therefore, to date, patients only receive symptomatic care, including the administration of first-generation antiepileptic drugs for seizure control. As data on the efficacy of drugs within this population are completely lacking, the aim of this study was to explore how therapeutic drug monitoring could help to understand the differential response to therapy. Considering the chall...
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Simultaneous Determination of Dabigatran, Rivaroxaban, and Apixaban in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry
Background:
Pharmacokinetic studies and therapeutic drug monitoring of anticoagulants require a simple, rapid, and reliable analytical method for monitoring plasma concentrations. The aims of the current work were to develop and validate a liquid chromatography/tandem mass spectrometry method for the simultaneous determination of 3 direct oral anticoagulants (dabigatran, rivaroxaban, and apixaban) in human plasma that is suitable for pharmacokinetic studies and routine therapeutic drug monitoring in busy hospital laboratories.
Methods:
This method included a hydrolysis step to account for the active acylglucuronide me...
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Routine Therapeutic Drug Monitoring of Dabigatran: Experience at a Tertiary Center
Background:
A liquid chromatography-mass spectrometry assay to determine plasma dabigatran concentrations has been available for routine clinical use at our tertiary institutions since 2017. The aim of the study was to describe (1) the use of the assay over time; (2) the indications for testing; and (3) subsequent dabigatran prescribing decisions.
Methods:
Patients for whom dabigatran concentrations were measured were identified using the laboratory database, and clinical data were extracted from the associated electronic health records.
Results:
There were 233 samples in 24 months. The use of dabigatran increased ...
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Clinical Validation of a Dried Blood Spot Assay for 8 Antihypertensive Drugs and 4 Active Metabolites
Conclusions:
A novel DBS assay for simultaneously qualifying and quantifying 8 AHDs and their metabolites, has been successfully developed and validated. The DBS assay is therefore a suitable method to detect drug nonadherence. However, with the exception of canrenone, the interchangeable use of plasma and DBS sampling to interpret drug quantities should be avoided. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Population Pharmacokinetics of Vancomycin Under Continuous Renal Replacement Therapy Using a Polymethylmethacrylate Hemofilter
In this study, the authors aimed to describe the population pharmacokinetics of VCM in critically ill patients undergoing PMMA-CHDF and clarify its hemofilter clearance (CLhemofilter).
Methods:
This single-center, retrospective study enrolled patients who underwent intravenous VCM therapy during PMMA-CHDF at the intensive care unit of Chiba University Hospital between 2008 and 2016. A population analysis was performed, and CLhemofilter was assessed.
Results:
Twenty-five patients were enrolled. Median body weight (BW) and Sequential Organ Failure Assessment (SOFA) score were 63 kg and 15, respectively. Mean conditions...
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Development and Validation of an UHPLC-MS/MS Assay for the Therapeutic Monitoring of Brivaracetam Plasma Concentrations in Patients with Epilepsy
Background:
Brivaracetam is an antiepileptic drug used as an add-on therapy for partial-onset seizures in subjects aged 4 years and older. Owing to potential drug interactions and intersubject variability in plasma concentrations, therapeutic monitoring for brivaracetam may be useful. The aim of this study was to develop a simplified method for measuring brivaracetam plasma concentrations applicable to therapeutic drug monitoring in epilepsy.
Methods:
An ultra high-pressure liquid chromatography–tandem mass spectrometry method was developed and validated according to current guidelines for bioanalytical methods. Sam...
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Therapeutic Drug Monitoring of Asparaginase: Intra-individual Variability and Predictivity in Children With Acute Lymphoblastic Leukemia Treated With PEG-Asparaginase in the AIEOP-BFM Acute Lymphoblastic Leukemia 2009 Study
Conclusions:
To use TDM as a basis for clinical decisions, standardized clinical procedures are required and high intra-individual variability should be taken into account. Details of the treatment are available in the European Clinical Trials Database at https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-004270-43/DE. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Limited Sampling Strategies Supporting Individualized Dose Adjustment of Intravenous Busulfan in Children and Young Adults
Background:
Therapeutic drug monitoring (TDM) for busulfan supports dose adjustment during conditioning for stem cell transplantation. The authors aimed to develop and validate limited sampling strategies (LSS) of 4–5 samples for a precise estimation of the area under concentration (AUC)-time curve of busulfan, in plasma as an alternative to an intensive sampling strategy (ISS) requiring 9–10 samples.
Methods:
ISS TDM data from 297 patients (≤18 years of age) were used. AUCLSS was calculated using the trapezoidal rule and multiple linear regression (MLR). Unlike more complex modeling methods, MLR does not requir...
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Long-Term Performance of Laboratory-Developed Liquid Chromatography–Tandem Mass Spectrometry Tests and a Food and Drug Administration–Approved Immunoassay for the Therapeutic Drug Monitoring of Everolimus
Conclusions:
Initially, QMS everolimus concentrations in patient samples were comparable with those detected in LC-MS/MS laboratories. However, concentration bias of the QMS assay significantly changed within 6 years, emphasizing the need for long-term, independent performance tracking of therapeutic drug monitoring assays, including FDA-approved assays. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Dosing Requirements of Extended-Release Tacrolimus (Astagraf XL) in African American Kidney Transplant Recipients Converted from Immediate-Release Tacrolimus (AAAKTRS)
Conclusions:
This single-center, open-label conversion study demonstrated that there was a statistically and clinically significant decrease in dose-normalized trough after conversion from tacrolimus IR to tacrolimus ER in an African American kidney transplant population and that a 1:1 dose conversion is unlikely to meet therapeutic goals. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Tacrolimus Area Under the Concentration Versus Time Curve Monitoring, Using Home-Based Volumetric Absorptive Capillary Microsampling
Conclusions:
Capillary microsampling is patient-centered, making AUC-targeted TDM of Tac feasible without extended hospital stays. Samples obtained 0, 1, and 3 hours after dose, combined with popPK-BE, accurately predict venous Tac AUC. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Comparison of 4 Commercial Immunoassays Used in Measuring the Concentration of Tacrolimus in Blood and Their Cross-Reactivity to Its Metabolites
Conclusions:
Each immunoassay was useful, but had its own characteristics. ACMIA cross-reactivities to M-II and M-III were much higher than the respective 18% and 15% reported on its package insert, suggesting that cross-reactivity should be examined at clinically relevant concentrations. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Evaluation of Concentration Errors and Inappropriate Dose Tailoring of Tacrolimus Caused by Sampling-Time Deviations in Pediatric Patients With Primary Nephrotic Syndrome
Background:
Tacrolimus dosing is routinely tailored based on its trough level (C0) drawn by therapeutic drug monitoring in pediatric patients with primary nephrotic syndrome. However, this concentration is often inaccurate owing to inappropriate practice, such as deviation of sampling time (DST). The quantitative relationship between DST and C0 remains unclear.
Methods:
Tacrolimus concentration at nominal sampling times (12 hours after last dose) and 32 deviation scenarios (12 ± 4 hours every 15 minutes) was predicted using a previously validated population pharmacokinetic model based on 162 scenarios of 100 primary ...
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Exposure Variability and Target Attainment of Vancomycin: A Systematic Review Comparing Intermittent and Continuous Infusion
Conclusions:
In conclusion, CoI was associated with lower variabilities in the serum concentration and favorable target attainment rates compared with InI. These findings are important because vancomycin exposure is considered a major predictor of the patients' clinical outcomes. However, the role of lower serum concentration variability and higher target attainment rates in achieving better clinical outcomes needs to be evaluated in patients treated with vancomycin CoI compared with InI. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Review Article Source Type: research
Significance of Ethnic Factors in Immunosuppressive Therapy Management After Organ Transplantation
Abstract:
Clinical outcomes after organ transplantation have greatly improved in the past 2 decades with the discovery and development of immunosuppressive drugs such as calcineurin inhibitors, antiproliferative agents, and mammalian target of rapamycin inhibitors. However, individualized dosage regimens have not yet been fully established for these drugs except for therapeutic drug monitoring-based dosage modification because of extensive interindividual variations in immunosuppressive drug pharmacokinetics. The variations in immunosuppressive drug pharmacokinetics are attributed to interindividual variations in the fun...
Source: Therapeutic Drug Monitoring - May 20, 2020 Category: Drugs & Pharmacology Tags: Review Article Source Type: research
