Search results for "Area Under Curve"
showing 10 items of 128 documents
Toward Biopredictive Dissolution for Enteric Coated Dosage Forms
2016
The aim of this work was to develop a phosphate buffer based dissolution method for enteric-coated formulations with improved biopredictivity for fasted conditions. Two commercially available enteric-coated aspirin products were used as model formulations (Aspirin Protect 300 mg, and Walgreens Aspirin 325 mg). The disintegration performance of these products in a physiological 8 mM pH 6.5 bicarbonate buffer (representing the conditions in the proximal small intestine) was used as a standard to optimize the employed phosphate buffer molarity. To account for the fact that a pH and buffer molarity gradient exists along the small intestine, the introduction of such a gradient was proposed for p…
Micronucleus frequencies and clonogenic cell survival in TK6 cells exposed to changing dose rates under controlled temperature conditions.
2014
In most exposure scenarios the dose rate of exposure is not constant. Despite this, very little information exists on the possible biological effects of exposing cells to radiation under the conditions of a changing dose rate. The current study highlights interesting effects following exposure under these conditions.We constructed a new exposure facility that allows exposing cells inside an incubator and used it to irradiate human lymphoblastoid TK6 cells both after a moderate (0.48 Gy) and a high (1.1 Gy) dose, where the change in dose rate was, respectively, ≈ 17-fold (2.2-37 mGy/min) and ≈ 39-fold (2.7-106 mGy/min). Clonogenic survival and micronuclei (MN) induction were the chosen endpo…
Compression-based classification of biological sequences and structures via the Universal Similarity Metric: experimental assessment.
2007
Abstract Background Similarity of sequences is a key mathematical notion for Classification and Phylogenetic studies in Biology. It is currently primarily handled using alignments. However, the alignment methods seem inadequate for post-genomic studies since they do not scale well with data set size and they seem to be confined only to genomic and proteomic sequences. Therefore, alignment-free similarity measures are actively pursued. Among those, USM (Universal Similarity Metric) has gained prominence. It is based on the deep theory of Kolmogorov Complexity and universality is its most novel striking feature. Since it can only be approximated via data compression, USM is a methodology rath…
Measuring the agreement between brain connectivity networks.
2016
Investigating the level of similarity between two brain networks, resulting from measures of effective connectivity in the brain, can be of interest from many respects. In this study, we propose and test the idea to borrow measures of association used in machine learning to provide a measure of similarity between the structure of (un-weighted) brain connectivity networks. The measures here explored are the accuracy, Cohen's Kappa (K) and Area Under Curve (AUC). We implemented two simulation studies, reproducing two contexts of application that can be particularly interesting for practical applications, namely: i) in methodological studies, performed on surrogate data, aiming at comparing th…
The Influence of Single-Dose and Short-Term Administration of Quercetin on the Pharmacokinetics of Midazolam in Humans.
2015
Quercetin is a plant flavonol that is available from both daily diet and nutraceuticals. To investigate the effect of acute and short-term intake of high-dose quercetin on CYP3A-mediated metabolism, 10 healthy volunteers received 7.5 mg oral midazolam without, with a single dose of 1500 mg quercetin and after 1-week supplementation with 1500 mg quercetin daily. A substudy was performed in three subjects to explore the impact of repeated quercetin intake on intravenously administered midazolam. Coadministration with a single dose of quercetin did not significantly alter the pharmacokinetics of midazolam and its 1'-hydroxymetabolite, but following short-term quercetin intake, there was a tren…
Computer simulations for bioequivalence trials: selection of analyte in BCS drugs with first-pass metabolism and two metabolic pathways.
2010
The objective of this work is to use a computer simulation approach to define the most sensitive analyte for in vivo bioequivalence studies of all types of Biopharmaceutics Classification System (BCS) drugs undergoing first-pass hepatic metabolism with two metabolic pathways. A semi-physiological model was developed in NONMEM VI to simulate bioequivalence trials. Four BCS classes (from Class I to IV) of drugs, with three possible saturation scenarios (non-saturation, saturation and saturation of only the major route of metabolism), two (high or low) dose schemes, and six types of pharmaceutical quality for the drug products were simulated. The number of investigated scenarios was 144 (4 × 3…
Computer simulations of bioequivalence trials: selection of design and analyte in BCS drugs with first-pass hepatic metabolism: linear kinetics (I).
2008
Modeling and simulation approaches are useful tools to assess the potential outcome of different scenarios in bioequivalence studies. The aim of this study is to propose a new and improved semi-physiological model for bioequivalence trial simulations and apply it for all BCS (Biopharmaceutic Classification System) drug classes with non-saturated first-pass hepatic metabolism. The semi-physiological model was developed in NONMEM VI to simulate bioequivalence trials. Parent drug and metabolite levels for both reference and test were simulated. Eight types of drugs (with high or low permeability and high or low solubility (class I to IV) and high or low intrinsic clearance) were considered in …
A multilevel object-oriented modelling methodology for physiologically-based pharmacokinetics (PBPK): Evaluation with a semi-mechanistic pharmacokine…
2019
Abstract Background and objective The aims of this study are (i) to assess the predictive reliability of the physiologically based software PhysPK versus the well-known population approach software NONMEM for the cited semi-mechanistic PK model, (ii) to determine whether these modelling approaches are interchangeable and (iii) to compare acausal with causal modelling approaches in the framework of semi-mechanistic PK models. Methods A semi-mechanistic model was proposed, which assumed oral administration of a solid dosage form with a peripheral compartment and two active metabolites. The model incorporates intestinal transit, dissolution limited by solubility, variable efflux transporter ex…
Contractile Reserve and Extent of Transmural Necrosis in the Setting of Myocardial Stunning: Comparison at Cardiac MR Imaging
2010
To perform a comparison of cardiac magnetic resonance (MR) imaging-derived ejection fraction (EF) during low-dose dobutamine infusion (EF(D)) with the extent of segments with transmural necrosis in more than 50% of their wall thickness (ETN) for the prediction of major adverse cardiac events (MACEs) and late systolic recovery soon after a first ST-segment elevation myocardial infarction (STEMI).Institutional ethics committee approval and written informed consent were obtained. One hundred nineteen consecutive patients with a first STEMI, a depressed left ventricular EF, and an open infarct-related artery underwent MR imaging at 1 week after infarction. EF(D) and ETN (by using a 17-segment m…
Late gadolinium enhancement-cardiovascular magnetic resonance identifies coronary artery disease as the aetiology of left ventricular dysfunction in …
2009
Aims We evaluated the ability of late gadolinium enhancement (LGE) using cardiovascular magnetic resonance (CMR) to identify acute new-onset heart failure (HF) with left ventricular systolic dysfunction (LVSD), whether or not in relation to underlying coronary artery disease (CAD), in patients with no clinical evidence of associated ischaemic cardiomyopathy. Methods and results Hundred consecutive patients admitted with acute new-onset decompensated HF and EF ,40%, with no clinical or electrocardiographic data suggestive of CAD. The patients were classified according to the presence or absence of significant CAD (stenosis � 70% in at least one major vessel). Twenty-one patients (21%) had si…