Introduction: Noscapine is a commonly used cough suppressant, with ongoing research on its anti-inflammatory and anti-tumor properties. The drug has a pronounced pharmacokinetic variability.
Objective: This evaluation aims to describe the pharmacokinetics of noscapine using a semi-mechanistic population pharmacokinetic model and to identify covariates that could explain inter-individual pharmacokinetic variability.
Purpose: Currently, body weight-based dosing of rifampicin is recommended. But lately, fat-free mass (FFM) was reported to be superior to body weight (BW). The present evaluation aimed to assess the influence of body mass-related covariates on rifampicin's pharmacokinetics (PK) parameters in more detail using non-linear mixed effects modeling (NLMEM).
View Article and Find Full Text PDFObjectives: Midostaurin is an oral multitargeted tyrosine kinase inhibitor for the treatment of acute myeloid leukemia (AML). Therapeutic drug monitoring of midostaurin may support its safe use when suspecting toxicity or combined with strong CYP3A4 inhibitors.
Methods: A stable isotope dilution liquid chromatography-tandem mass spectrometry method was developed and validated for the determination and quantification of midostaurin in human plasma and serum.
Peripheral neuropathy is a common side effect of cancer treatment with paclitaxel. The mechanisms by which paclitaxel is transported into neurons, which are essential for preventing neuropathy, are not well understood. We studied the uptake mechanisms of paclitaxel into neurons using inhibitors for endocytosis, autophagy, organic anion-transporting polypeptide (OATP) drug transporters, and derivatives of paclitaxel.
View Article and Find Full Text PDFGlia are critical players in defining synaptic contacts and maintaining neuronal homeostasis. Both astrocytes as glia of the central nervous system (CNS), as well as satellite glial cells (SGC) as glia of the peripheral nervous system (PNS), intimately interact with microglia, especially under pathological conditions when glia regulate degenerative as well as regenerative processes. The chemotherapeutic agent paclitaxel evokes peripheral neuropathy and cognitive deficits; however, the mechanisms underlying these diverse clinical side effects are unclear.
View Article and Find Full Text PDFPeripheral neuropathy is a common side effect of paclitaxel. Clinical studies suggest that different paclitaxel formulations influence the severity and time course of paclitaxel-induced peripheral neuropathy. We compared two paclitaxel formulations, nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and Cremophor EL paclitaxel (CreEL-paclitaxel), for their toxicity, distribution, and clearance in the peripheral nervous system.
View Article and Find Full Text PDFPurpose: The purpose of this study was to gain insights on the pathogenesis of chronic progressive external ophthalmoplegia, thus we investigated the vulnerability of five extra ocular muscles (EOMs) fiber types to pathogenic mitochondrial DNA deletions in a mouse model expressing a mutated mitochondrial helicase TWINKLE.
Methods: Consecutive pairs of EOM sections were analyzed by cytochrome C oxidase (COX)/succinate dehydrogenase (SDH) assay and fiber type specific immunohistochemistry (type I, IIA, IIB, embryonic, and EOM-specific staining).
Results: The mean average of COX deficient fibers (COX-) in the recti muscles of mutant mice was 1.
Purpose: Chronic graft versus host disease is a major consequence after allogeneic stem cell transplantation (allo-SCT) and has great impact on patients' morbidity and mortality. Besides the skin, liver, and intestines, the eyes are most commonly affected, manifesting as severe ocular surface disease. Treatment protocols include topical steroids, cyclosporine, tacrolimus, and ASED.
View Article and Find Full Text PDFMinerva Pediatr (Torino)
April 2021
Introduction: Critically ill patients in neonatal intensive-care units (NICU) are exposed to a large number of drugs. Clinical trials for safety, dosing and efficacy are lacking although age-dependent alterations of pharmacokinetics (PK), drug-drug-interactions (DDIs), as well as intravenous admixture incompatibilities (IAI) may impact drug efficacy and trigger side-effects in this vulnerable population. Consequently, implementation of a routinely used DDIs checking regimen may help guide in decision making and will assist clinicians to avoid serious and preventable events.
View Article and Find Full Text PDFBackground: Under certain circumstances, clinicians treating patients with isavuconazole for invasive aspergillosis or mucormycosis may use therapeutic drug monitoring. However, the accuracy and reproducibility of the various assays used by different laboratories for the quantification of isavuconazole plasma concentrations have yet to be determined.
Methods: Human plasma samples spiked with known concentrations of isavuconazole were provided to 27 European laboratories that took part in a "round-robin" test (an interlaboratory test performed independently at least 2 times; 2 rounds performed in the current study).
Background: Mycophenolic acid (MPA), a powerful inhibitor of lymphocyte proliferation, is widely used in transplantation medicine and as a glucocorticoid-sparing agent in rheumatic and inflammatory diseases. As inosine-5'-monophosphate dehydrogenase (IMPDH), the target enzyme of MPA, shows high interindividual variability in its basal activity, the assessment of IMPDH activity in addition to pharmacokinetic monitoring has emerged as a strategy to individualize MPA pharmacotherapy.
Methods: A liquid chromatography-tandem mass spectrometry method was developed to measure IMPDH activity in peripheral blood mononuclear cells from lithium-heparinized blood.
Background: Serious bleeding events have been frequently described in patients taking direct oral anticoagulants (DOAC). In secondary analyses of phase 3 trials, DOAC plasma concentrations were shown to correlate with bleeding outcomes. This study aimed to describe rivaroxaban plasma levels in patients admitted to the emergency department (ED) for bleeding events.
View Article and Find Full Text PDFBackground: Therapy-refractory arterial hypertension is defined as a blood pressure (BP) in a subset of patients who fail to achieve BP control despite a three-drug regimen (including a diuretic). Various factors have impact on loss of therapy response. Drug-drug-interactions (DDIs) may cause altered pharmacokinetics (PK) of antihypertensive drugs.
View Article and Find Full Text PDFBackground: Analgosedation is a cornerstone therapy for mechanically ventilated patients in intensive care units (ICU). To avoid inadequate sedation and its complications, monitoring of analgosedation is of great importance. The aim of this study was to investigate whether monitoring of analgosedative drug concentrations (midazolam and sufentanil) might be beneficial to optimize analgosedation and whether drug serum concentrations correlate with the results of subjective (Richmond Agitation-Sedation Scale [RASS]/Ramsay Sedation Scale) and objective (bispectral (BIS) index) monitoring procedures.
View Article and Find Full Text PDFAntimicrob Agents Chemother
November 2018
A fast and easy-to-use liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of a novel antifungal drug, olorofim (F901318), a member of the novel class of orotomides, in human plasma and serum was developed and validated. Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation. An isotope-labeled analogue of F901318 was employed as an internal standard.
View Article and Find Full Text PDFPurpose: Patients treated with direct oral anticoagulants (DOACs) frequently undergo interventional procedures requiring temporary discontinuation of anticoagulant therapy. Little is known about remaining peri-procedural exposure to rivaroxaban in real-world patients.
Methods: Fifty-six patients with rivaroxaban treatment and scheduled cardiac catheterization were included in this prospective, observational, and single-center study.
Background: A fast and easy-to-use liquid chromatography-tandem mass spectrometry method for the determination and quantification of 6 triazoles [fluconazole (FLZ), isavuconazole (ISZ), itraconazole (ITZ), hydroxy-itraconazole (OH-ITZ), posaconazole (PSZ), and voriconazole (VRZ)] in human plasma and serum was developed and validated for therapeutic drug monitoring.
Methods: Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation. Isotope-labeled analogues for each analyte were used as internal standards.
Background: Assessment of the anticoagulant activity of direct oral anticoagulants (DOACs) is justified in special clinical situations. Here, we evaluated two independent extraction methods and developed a multi-analyte ultra-high performance liquid chromatography tandem mass (UHPLC-MS/MS) method for the quantification of apixaban, dabigatran, edoxaban and rivaroxaban in human plasma.
Methods: Routine extraction based on protein precipitation with acetonitrile and subsequent centrifugation was compared to sample clean-up using commercial paramagnetic micro-particles and subsequent magnetic depletion.
Thromboembolic disorders frequently require antithrombotic treatment during pregnancy and lactation. Vitamin K antagonists and heparins are the treatment options of choice in breastfeeding women. Factors including the route of administration, discomfort during treatment, and fetal and neonatal safety affect women's choices about anticoagulant therapy.
View Article and Find Full Text PDFBackground: The non-vitamin K antagonist oral anticoagulants (NOACs) apixaban, dabigatran, and rivaroxaban are being administered in fixed doses without routine monitoring of anticoagulant activities. Despite this key advantage over vitamin K antagonists (VKAs), assessment of anticoagulant intensities is required in various clinical circumstances. We developed a multi-analyte approach for mass spectrometric analysis of NOACs in human plasma.
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