Search results for "First pass"
showing 10 items of 20 documents
Automatic fuzzy classification of the washout curves from magnetic resonance first-pass perfusion imaging after myocardial infarction.
2005
International audience; Abstract: Objectives: We sought to investigate the diagnostic ability of cardiac magnetic resonance imaging (MRI) perfusion in acute reper-fused myocardial infarction. The study used fuzzy logic to automatically classify signal intensity-time curves from myocardial segments into 3 categories: normal, hypointense, and Hyperintense. Materials and Methods: Thirty-eight patients with myocardial infarction underwent short-axis cine-MRI and contrast-enhanced MRI to provide data on wall thickening and the transmural extent of infarction. Of these, 17 had a second cardiac MRI to ascertain the functional recovery in each segment. Results: The fuzzy logic based classification …
Pharmacokinetics of triamterene after i.v. administration to man: determination of bioavailability.
1983
With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. …
On reliability of systems with moving material subjected to fracture and instability
2015
Abstract The reliability of systems with moving cracked elastic and isotropic material is considered. The material is modeled as a moving plate which continually has a crack on the edge. The plate is subjected to homogeneous tension acting in the traveling direction and the tension varies temporally around a constant value, the set tension. The tension and the length of the crack are modeled by an Ornstein–Uhlenbeck process and an exponential Ornstein–Uhlenbeck process, respectively. Failure is regarded as the state at which the plate becomes unstable or fractures (or both) and a lower bound for the reliability of the system is derived. Considering reliability of the system leads to first p…
Semi-physiologic model validation and bioequivalence trials simulation to select the best analyte for acetylsalicylic acid
2015
Abstract The objective of this paper is to apply a previously developed semi-physiologic pharmacokinetic model implemented in NONMEM to simulate bioequivalence trials (BE) of acetyl salicylic acid (ASA) in order to validate the model performance against ASA human experimental data. ASA is a drug with first-pass hepatic and intestinal metabolism following Michaelis–Menten kinetics that leads to the formation of two main metabolites in two generations (first and second generation metabolites). The first aim was to adapt the semi-physiological model for ASA in NOMMEN using ASA pharmacokinetic parameters from literature, showing its sequential metabolism. The second aim was to validate this mod…
Computer simulations for bioequivalence trials: Selection of analyte in BCS class II and IV drugs with first-pass metabolism, two metabolic pathways …
2018
A semi-physiological two compartment pharmacokinetic model with two active metabolites (primary (PM) and secondary metabolites (SM)) with saturable and non-saturable pre-systemic efflux transporter, intestinal and hepatic metabolism has been developed. The aim of this work is to explore in several scenarios which analyte (parent drug or any of the metabolites) is the most sensitive to changes in drug product performance (i.e. differences in in vivo dissolution) and to make recommendations based on the simulations outcome. A total of 128 scenarios (2 Biopharmaceutics Classification System (BCS) drug types, 2 levels of KM Pgp, in 4 metabolic scenarios at 2 dose levels in 4 quality levels of t…
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…
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 …
Reliability analysis of processes with moving cracked material
2015
Abstract The reliability of processes with moving elastic and isotropic material containing initial cracks is considered in terms of fracture. The material is modelled as a moving plate which is simply supported from two of its sides and subjected to homogeneous tension acting in the travelling direction. For tension, two models are studied: (i) tension is constant with respect to time, and (ii) tension varies temporally according to an Ornstein–Uhlenbeck process. Cracks of random length are assumed to occur in the material according to a stochastic counting process. For a general counting process, a representation of the nonfracture probability of the system is obtained that exploits condi…
Quantification of Myocardial Blood Flow Using Magnetic Resonance Imaging with Different accelerated Pulse Sequences
2009
The aim of this study was to compare SRTurboFLASH, SR-TrueFISP, and SR-segEPI pulse sequences using a twofold TSENSE-acceleration with regard to their use in quantification of myocardial blood flow (MBF). Six healthy volunteers were examined at 1.5T by first pass myocardial perfusion MRI at rest using all three TSENSE-accelerated pulse sequences. For absolute quantifi-cation of MBF XSIM software with the MMID4 model has been used. MBF analyses revealed significant MBF differences between SRTurboFLASH and SR-segEPI compared to SR-TrueFISP (p<0.005 and p<0.001, respectively). Differences between SRTurboFLASH and SR-segEPI were not statistically significant. The median MBF values for SR-TurboF…
Evidence for Early Closure Attachment on First Pass Reading Times in French
1997
An eye-tracking experiment was conducted in French with sentences of the form “N V N1of-N2 who …” Example: “A journalist approached the barrister (male) of the singer (female) who seemed more confident (masculine or feminine gender) than (s)he ought to be.” The results are consistent with those of Cuetos and Mitchell (1988). French readers, like Spanish readers, prefer early closure (and are garden-pathed when the sentence turns out to be a late-closure attachment). This effect was exhibited by first-pass reading times that are usually assumed to reflect initial syntactic commitments. These results are discussed in relation to Frazier and Clifton's recent proposals concerning attachment me…