Comparison of Novel Immunoassay With Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) for Therapeutic Drug Monitoring of Clozapine
Background:
Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia. Although serum clozapine levels can help guide treatment, they are underutilized owing to requirements for frequent venous blood draws and lack of immediate results.
Methods:
Clozapine levels measured with a novel immunoassay technology (which enables point-of-care development) were compared with those measured by standard liquid chromatography/tandem mass spectrometry (LC-MS/MS). Frozen serum aliquots of 117 samples (N = 48 patients with schizophrenia on clozapine; N = 24 patients with schizophrenia not on clozapine; N = ...
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Association Between the Serum Carnitine Level and Ammonia and Valproic Acid Levels in Patients with Bipolar Disorder
Conclusions:
These findings suggest that carnitine deficiency is associated with the VPA dose and the serum VPA level in patients with bipolar disorder. However, it is unlikely that carnitine deficiency is associated with hyperammonemia in patients with bipolar disorder. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Impact of Age and Genotype on Serum Concentrations of Valproic Acid and Its Hepatotoxic Metabolites in Chinese Pediatric Patients With Epilepsy
Conclusions:
The present study suggests that UGT2B7 802C>T polymorphism and age are factors affecting the concentrations of dose-adjusted VPA and its metabolites. No genotype-related differences were noted in the metabolite ratios of 4-ene-VPA and 2,4-diene-VPA within age-assigned groups. Therefore, careful administration is particularly necessary for younger patients who are UGT2B7 802C>T poor metabolizers. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Therapeutic Monitoring of Lacosamide in Japanese Patients With Epilepsy: Clinical Response, Tolerability, and Optimal Therapeutic Range
Background:
Lacosamide is a novel anticonvulsant that acts by enhancing sodium channel slow inactivation. The aims of this study were to evaluate the influence of concomitant antiepileptic drugs (AEDs) on serum lacosamide concentration and explore the relationship between lacosamide serum concentration and both clinical response and adverse effects.
Methods:
The authors analyzed 649 serum samples from 426 Japanese patients with epilepsy. The concentration-to-dose (CD) ratio of lacosamide was compared among patients on various AED regimens. Clinical information about seizure frequency and adverse events was obtained fr...
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Pharmacokinetic Variability During Long-Term Therapeutic Drug Monitoring of Valproate, Clobazam, and Levetiracetam in Patients With Dravet Syndrome
This study included patients with Dravet syndrome as they often require close monitoring because of polypharmacy with various ASMs. The aim was to use long-term TDM to investigate pharmacokinetic variability of ASMs in these patients.
Methods:
Retrospective data from patients with Dravet syndrome were collected from the TDM database at the Section for Clinical Pharmacology, National Center for Epilepsy in Norway (2008–2018). Concentration/(dose/kg)ratios (C/D ratios) were calculated for the ASMs and the concentration (C/C ratio) for N-desmethylclobazam. In patients with at least 3 measurements, the CV for C/D ratios f...
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Perils of Antithrombotic Transitions: Effect of Oral Factor Xa Inhibitors on the Heparin Antifactor Xa Assay
Conclusions:
This study assessed the prevalence of supratherapeutic antiXa levels and clinical outcomes during the transition from OFXais to UFH. Health care systems should develop guidelines to assist clinicians in monitoring antiXa activity in patients undergoing a transition from an OFXai to UFH. It is also important to assess the patient's underlying thromboembolic and bleeding risks. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Cefotiam Treatment in Children: Evidence of Subtherapeutic Levels
Background:
Cefotiam, a second-generation cephalosporin, is a broad-spectrum antibiotic with good antibacterial action against both gram-negative and gram-positive bacteria. It is used widely in clinical practice, although bacterial drug resistance makes its clinical use problematic. The authors hypothesized that subtherapeutic concentrations of cefotiam leads to bacterial resistance. The present study was conducted to evaluate whether the standard cefotiam dosing regimen resulted in a subtherapeutic concentrations in children.
Method:
Data were prospectively collected from pediatric patients with suspected or confirm...
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Quantification of Serum Sulfamethoxazole and Trimethoprim by Ultra-fast Solid-Phase Extraction–Tandem Mass Spectrometry
Background:
The combination of trimethoprim (TMP) and sulfamethoxazole (SMX) is used to treat a number of bacterial infections. TMP/SMX concentrations in serum are conventionally monitored using high-performance liquid chromatography (HPLC) or liquid chromatography tandem mass spectrometry. These methods require laborious manual extraction techniques and relatively long sample analysis times, necessitating the development of a simple, high-throughput method. A simple, high-throughput method to measure TMP/SMX using ultra-fast solid-phase extraction (SPE)–tandem mass spectrometry has been developed.
Methods:
Calibrat...
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
A Simple and Robust Liquid Chromatography With Tandem Mass Spectrometry Analytical Method for Therapeutic Drug Monitoring of Plasma and Cerebrospinal Fluid Polymyxin B1 and B2
Conclusions:
A simple and robust method to measure polymyxin B1 and B2 in human CSF was first exploited and validated with good sensitivity and specificity, and successfully applied in polymyxin B pharmacokinetic analysis and therapeutic monitoring in Chinese patients. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Evaluation of Assays to Measure Aminoglycosides in Serum: Comparison of Accuracy and Precision Based on External Quality Assessment
Conclusions:
This study demonstrated high variations in results obtained from antibiotic assays conducted at different laboratories worldwide. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
No Apparent Influence of Nonadherence on Tacrolimus Intrapatient Variability in Stable Kidney Transplant Recipients
Conclusions:
There was no apparent relationship between IPV and nonadherence in this motivated kidney transplant recipient population, with one missed tacrolimus dose every 2 weeks. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Salting Out-Assisted Liquid–Liquid Extraction for Liquid Chromatography–Tandem Mass Spectrometry Measurement of Tacrolimus, Sirolimus, Everolimus, and Cyclosporine a in Whole Blood
Conclusions:
This is the first report of the use of SALLE for the measurement of tacrolimus, sirolimus, everolimus, and cyclosporine A in whole blood. The advantages of SALLE over PPT and conventional LLE would make it an attractive sample preparation method for clinical laboratories. (Source: Therapeutic Drug Monitoring)
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Establishment of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Immunosuppressant Levels in the Peripheral Blood Mononuclear Cells of Chinese Renal Transplant Recipients
Background:
Monitoring immunosuppressant levels, such as mycophenolic acid (MPA), cyclosporin A (CsA), and tacrolimus (TAC), in peripheral blood mononuclear cells (PBMCs) could be useful in organ transplant patients administered individualized therapy. The authors developed a liquid chromatography-tandem mass spectrometry assay technique to simultaneously determine immunosuppressant levels in PBMCs and assess their pharmacokinetics in Chinese renal allograft recipients.
Methods:
PBMCs were isolated from the whole blood of 27 Chinese renal transplant patients using Ficoll-Paque Plus solution, and cell number was determ...
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Chronopharmacokinetics and Food Effects of Single-Dose LCP-Tacrolimus in Healthy Volunteers
Background:
A modified-release version of tacrolimus, LCP-tacrolimus (LCPT; Envarsus XR, Veloxis Pharmaceuticals, Cary, NC), has been licensed in the United States for prophylaxis of organ rejection in de novo kidney transplant patients. As tacrolimus has a narrow therapeutic window, the impact of circadian patterns on LCPT drug exposure, including food and chronopharmacokinetic effects, needs to be elucidated to optimize dosing.
Methods:
Two randomized, crossover, phase 1 studies were conducted in healthy volunteers. The first assessed the effect of morning versus evening dosing on the pharmacokinetic profile of LCPT...
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Redefining Therapeutic Drug Monitoring of Tacrolimus in Patients Undergoing Liver Transplantation: A Target Trough Concentration of 4–7 ng/mL During the First Month After Liver Transplantation is Safe and Improves Graft and Renal Function
This study evaluated the efficacy of a target TAC Cmin of 4–7 ng/mL after LT.
Methods:
Of 1677 LTs performed between 2002 and 2017, 904 LT cases were analyzed. The cases were categorized into the following 3 groups and compared: low- (n = 247, 27.3%), intermediate- (n = 344, 37.9%), and high-exposure groups (n = 313, 34.5%) with TAC Cmin of 4–7 ng/mL, 7–10 ng/mL, and>10 ng/mL, respectively. In addition, propensity score matching was performed to reduce heterogeneity and population bias.
Results:
At months 1 and 3, when compared with the 2 other groups, the low-exposure group had similar grafts (P = 0.75) and pa...
Source: Therapeutic Drug Monitoring - September 25, 2020 Category: Drugs & Pharmacology Tags: Original Article Source Type: research
