Search results for "First pass"
showing 10 items of 20 documents
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…
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. …
First-passage problem for nonlinear systems under Lévy white noise through path integral method
2016
In this paper, the first-passage problem for nonlinear systems driven by $$\alpha $$ -stable Levy white noises is considered. The path integral solution (PIS) is adopted for determining the reliability function and first-passage time probability density function of nonlinear oscillators. Specifically, based on the properties of $$\alpha $$ -stable random variables and processes, PIS is extended to deal with Levy white noises with any value of the stability index $$\alpha $$ . Application to linear and nonlinear systems considering different values of $$\alpha $$ is reported. Comparisons with pertinent Monte Carlo simulation data demonstrate the accuracy of the results.
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 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…
Low bioavailability of amoxicillin in rats as a consequence of presystemic degradation in the intestine.
1994
Several studies have been carried out to elucidate the causes of the low oral bioavailability of amoxicillin in rats. The hepatic first-pass effect of the antibiotic was estimated by comparing the area under the plasma drug concentration-versus-time curve from time zero to infinity (AUC0-infinity) obtained after injecting the drug into a mesenteric vein with the AUC0-infinity value obtained after injecting the drug into the jugular vein of conscious rats. No hepatic first-pass effect was detected. The bioavailability of amoxicillin after intraduodenal administration was only 51%, and the fraction of the dose remaining in the intestine at the end of the experiment was 4.5%. This was far less…
Diffusive behavior and the modeling of characteristic times in limit order executions
2007
We present an empirical study of the first passage time (FPT) of order book prices needed to observe a prescribed price change Delta, the time to fill (TTF) for executed limit orders and the time to cancel (TTC) for canceled ones in a double auction market. We find that the distribution of all three quantities decays asymptotically as a power law, but that of FPT has significantly fatter tails than that of TTF. Thus a simple first passage time model cannot account for the observed TTF of limit orders. We propose that the origin of this difference is the presence of cancellations. We outline a simple model, which assumes that prices are characterized by the empirically observed distribution …
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…
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…
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…