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Time Profiles (time + profile)
Selected AbstractsEvidence for the Microwave Effect During the Annealing of Zinc OxideJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 9 2007J. Binner A microwave/conventional hybrid furnace has been used to anneal virtually fully dense zinc oxide ceramics under pure conventional and a microwave/conventional hybrid heating regime with a view to obtaining evidence for the "microwave effect" during the resulting grain growth. In each case it was ensured that each sample within a series had an identical thermal history in terms of its temperature/time profile. The results showed that grain growth was enhanced during hybrid heating compared with pure conventional heating; the greatest enhancement, a factor of ,3 increase in average grain size, was observed in the range 1100°,1150°C. The grain growth exponent decreased from 3 during conventional heating to 1.4 during hybrid heating in this temperature range, suggesting an acceleration of the diffusional processes involved. Temperature gradients within the samples were found to be too small to explain the results. This suggests that clear evidence has been found to support the existence of a genuine "microwave effect." [source] Estimating the Effects of a Time-Limited Earnings Subsidy for Welfare-LeaversECONOMETRICA, Issue 6 2005David Card In the Self Sufficiency Project (SSP) welfare demonstration, members of a randomly assigned treatment group could receive a subsidy for full-time work. The subsidy was available for 3 years, but only to people who began working full time within 12 months of random assignment. A simple optimizing model suggests that the eligibility rules created an "establishment" incentive to find a job and leave welfare within a year of random assignment, and an "entitlement" incentive to choose work over welfare once eligibility was established. Building on this insight, we develop an econometric model of welfare participation that allows us to separate the two effects and estimate the impact of the earnings subsidy on welfare entry and exit rates among those who achieved eligibility. The combination of the two incentives explains the time profile of the experimental impacts, which peaked 15 months after random assignment and faded relatively quickly. Our findings suggest that about half of the peak impact of SSP was attributable to the establishment incentive. Despite the extra work effort generated by SSP, the program had no lasting impact on wages and little or no long-run effect on welfare participation. [source] Capital Allocation and Risk Performance Measurement In a Financial InstitutionFINANCIAL MARKETS, INSTITUTIONS & INSTRUMENTS, Issue 5 2000Stuart M. Turnbull This paper provides an analytical and practical framework, consistent with maximizing the wealth of existing shareholders, to address the following questions: What are the costs associated with economic capital? What is the tradeoff between the probability of default and the costs of economic capital? How do we take into account the time profile of economic capital when assessing the performance of a business? What is the appropriate measure of profitability, keeping the probability of default constant? It is shown that the capital budgeting decision depends not only on the covariance of the return of a project with the market portfolio, but also on the covariance with the bank's existing assets. This dependency arises from the simple fact that the economic capital is not additive. [source] Design and Fabrication of Magnetically Functionalized Core/Shell Microspheres for Smart Drug DeliveryADVANCED FUNCTIONAL MATERIALS, Issue 2 2009Xiuqing Gong Abstract The fabrication of magnetically functionalized core/shell microspheres by using the microfluidic flow-focusing (MFF) approach is reported. The shell of each microsphere is embedded with magnetic nanoparticles, thereby enabling the microspheres to deform under an applied magnetic field. By encapsulating a drug, for example, aspirin, inside the microspheres, the drug release of the microspheres is enhanced under the compression,extension oscillations that are induced by an AC magnetic field. This active pumping mode of drug release can be controlled by varying the frequency and magnitude of the applied magnetic field as well as the time profile of the magnetic field. UV absorption measurements of cumulative aspirin release are carried out to determine the influence of these factors. The drug release behavior is found to be significantly different depending on whether the applied field varies sinusoidally or in a step-function manner with time. [source] Retention of 125I-labeled recombinant human bone morphogenetic protein-2 by biphasic calcium phosphate or a composite sponge in a rabbit posterolateral spine arthrodesis modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2002John Louis-Ugbo The purpose of this study was to characterize the retention kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) applied to two calcium-based delivery matrices. Biphasic calcium phosphate (BCP) and a composite containing BCP in an absorbable collagen sponge (BCP/ACS) were evaluated using a spinal fusion model in rabbits. rhBMP-2 labeled with radioactive iodine (125I) was used as a tracer to assess in vivo retention of rhBMP-2 in the presence of these materials (nine animals per material studied). Over a 36 day study period, animals were assessed for the following: percent administered dose retained at the implant site as measured by scintigraphic imaging (counting) with a gamma camera (all animals), radiography of the implant site (all animals), radioactivity in blood and plasma (all animals), and radioactivity in the urine and feces (three animals for each material). Radioactivity data were corrected for the decay of 125I and the attenuation between the implant in vivo and the gamma camera. Differences observed between the two materials for the area under the retention vs. time profile (AUC; 988%day for BCP vs. 1070%day for BCP/ACS, p = 0.57) and the mean residence time (MRT; 10.2 days for BCP vs. 7.6 days for BCP/ACS, p = 0.06) were not statistically significant. Initial retention/incorporation of rhBMP-2 was slightly higher for rhBMP-2/BCP/ACS than for rhBMP-2/BCP (96.8% vs. 86.0%, p lt; 0.05). Animals receiving rhBMP-2/BCP showed a longer terminal retention half-life (t1/2) than did those receiving rhBMP-2/BCP/ACS (7.5 vs. 4.5 days, p < 0.05). The urinary radioactivity recovery data supported the data obtained by scintigraphy. Over the 36 day collection period, essentially complete recovery of radioactivity (dose) in urine was observed for rhBMP-2/BCP and rhBMP-2/BCP/ACS and the majority of the radioactivity (approximately 95%) was soluble in trichloroacetic acid, suggesting extensive catabolism of rhBMP-2 before renal excretion. Fecal recovery of radioactivity was low, approximately 2,3%. In conclusion, rhBMP-2 was retained at the implant site when delivered with either BCP or BCP/ACS based on mean residence time and area under the retention curve vs. time profile. Use of these matrices resulted in detectable rhBMP-2 levels at the surgical site for over a week in contrast to data reported with several other matrices that lasted less time. Systemic catabolism and elimination of the rhBMP-2 was extensive and systemic presence of the protein was negligible. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Extrapolating in vitro metabolic interactions to isolated perfused liver: Predictions of metabolic interactions between R -bufuralol, bunitrolol, and debrisoquineJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2010Sami Haddad Abstract Drug,drug interactions (DDIs) are a great concern to the selection of new drug candidates. While in vitro screening assays for DDI are a routine procedure in preclinical research, their interpretation and relevance for the in vivo situation still represent a major challenge. The objective of the present study was to develop a novel mechanistic modeling approach to quantitatively predict DDI solely based upon in vitro data. The overall strategy consisted of developing a model of the liver with physiological details on three subcompartments: the sinusoidal space, the space of Disse, and the cellular matrix. The substrate and inhibitor concentrations available to the metabolizing enzyme were modeled with respect to time and were used to relate the in vitro inhibition constant (Ki) to the in vivo situation. The development of the liver model was supported by experimental studies in a stepwise fashion: (i) characterizing the interactions between the three selected drugs (R -bufuralol (BUF), bunitrolol (BUN), and debrisoquine (DBQ)) in microsomal incubations, (ii) modeling DDI based on binary mixtures model for all the possible pairs of interactions (BUF,BUN, BUF,DBQ, BUN,DBQ) describing a mutual competitive inhibition between the compounds, (iii) incorporating in the binary mixtures model the related constants determined in vitro for the inhibition, metabolism, transport, and partition coefficients of each compound, and (iv) validating the overall liver model for the prediction of the perfusate kinetics of each drug determined in isolated perfused rat liver (IPRL) for the single and paired compounds. Results from microsomal coincubations showed that competitive inhibition was the mechanism of interactions between all three compounds, as expected since those compounds are all substrates of rat CYP2D2. For each drug, the Ki values estimated were similar to their Km values for CYP2D2 indicative of a competition for the same substrate-binding site. Comparison of the performance between the novel liver physiologically based pharmacokinetic (PBPK) model and published empirical models in simulating the perfusate concentration,time profile was based on the area under the curve (AUC) and the shape of the curve of the perfusate time course. The present liver PBPK model was able to quantitatively predict the metabolic interactions determined during the perfusions of mixtures of BUF,DBQ and BUN,DBQ. However, a lower degree of accuracy was obtained for the mixtures of BUF,BUN, potentially due to some interindividual variability in the relative proportion of CYP2D1 and CYP2D2 isoenzymes, both involved in BUF metabolism. Overall, in this metabolic interaction prediction exercise, the PBPK model clearly showed to be the best predictor of perfusate kinetics compared to more empirical models. The present study demonstrated the potential of the mechanistic liver model to enable predictions of metabolic DDI under in vivo condition solely from in vitro information. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4406,4426, 2010 [source] Pharmacokinetics of liquiritigenin in mice, rats, rabbits, and dogs, and animal scale-upJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2009Hee E. Kang Abstract Pharmacokinetics of liquiritigenin (LQ) and its two glucuronide metabolites, M1 and M2, in mice, rats, rabbits, and dogs and animal scale-up of the pharmacokinetic parameters of LQ were evaluated. After intravenous administration of LQ, the AUC (AUC0,t) values of LQ, M1, and M2 were proportional to LQ doses in all animals studied. Animal scale-up of some pharmacokinetic parameters of LQ was performed based on the parameters after its intravenous administration (20 mg/kg; in the linear pharmacokinetic range) to the four species. Linear relationships were obtained (r,>,0.968) between log CL (or CL/fu) (L/h) and log species body weight (W) (kg) [CL (or CL/fu),=,3.29 (34.0) W0.723 (0.789)] and log,Vss (or Vss/fu) (L) and log,W (kg) [Vss (or Vss/fu),=,0.340 (3.52) W0.882 (0.948)]. Interspecies scale-up of plasma concentration,time data of LQ using apolysichron (complex Dedrick plots) resulted in similar profiles, and plasma concentration,time profile of humans were predicted using the well-fitted four animal data. Our results indicate that the LQ data obtained from laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters of LQ in humans. These parameters can serve as guidelines for better planning of clinical studies. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4327,4342, 2009 [source] Thiomers in noninvasive polypeptide delivery: In vitro and in vivo characterization of a polycarbophil-cysteine/glutathione gel formulation for human growth hormoneJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2004Verena M. Leitner Abstract This study was aimed at investigating the potential of a new polycarbophil-cysteine (PCP-Cys)/glutathione (GSH) gel formulation to enhance the permeation of the model drug human growth hormone (hGH) across nasal mucosa in vitro and in vivo. The aqueous nasal gel contained PCP-Cys, GSH, and hGH in a final concentration of 0.3%, 0.5%, and 0.6% (m/v), respectively. In vitro permeation studies were performed in Ussing chambers on freshly excised bovine nasal mucosa using fluorescence-labeled dextran (molecular mass: 4.3 kDa; FD-4) and hGH (FITC-hGH). The release profile of FITC-hGH from the gel formulation and an unmodified PCP control formulation was determined. Furthermore, in vivo studies in rats were performed comparing the PCP-Cys/GSH/hGH gel with PCP/hGH control gel and physiological saline. The permeation of FD-4 and FITC-hGH across the nasal mucosa was improved two-fold and three-fold, respectively, in the presence of PCP-Cys/GSH. The PCP-Cys/GSH/hGH gel and the PCP/hGH control gel showed the same biphasic and matrix-controlled drug release. The nasal administration of the PCP-Cys/GSH/hGH gel formulation to rats resulted in a significantly increased and prolonged hGH plasma concentration,time profile versus unmodified PCP gel and physiological saline. According to these results, PCP-Cys gels might represent a promising new strategy for systemic nasal polypeptide delivery. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1682,1691, 2004 [source] Applications of non-steady-state kinetics in physical organic chemistry: guidelines for the resolution of the kinetics of complex reaction mechanismsJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 9 2001Vernon D. Parker Abstract The resolution of the kinetics of the reversible consecutive second-order reaction mechanism involving the formation of a kinetically significant intermediate, which does not reach steady state before late in the first half-life, followed by an irreversible product-forming reaction is discussed. It is shown that an apparent second-order rate constant kapp and an extent of reaction,time profile are the only experimental data necessary for the evaluation of kf and kb (the forward and reverse rate constants) as well as kp (the microscopic rate constant for the product forming reaction). When the product-forming step involves the cleavage of a CH bond, for which there is a deuterium kinetic isotope effect on kp, the resolution of the kinetics is enhanced. In this case, the experimental data include two apparent rate constants ( and ) and two extent of reaction,time profiles, one for normal reactants and the other for isotopically substituted reactants. Under these circumstances, a unique highly resolved experimental to theoretical data fit is found that results in the evaluation of all four microscopic rate constants: and . An alternative, when a kinetic isotope effect is not involved, is to fit the extent of reaction,time profiles for two or more concentrations of reactants concurrently. This procedure results in the resolution of the three microscopic rate constants for the reaction. Copyright © 2001 John Wiley & Sons, Ltd. [source] Investigation of Japanese quail (Coturnix japonica) as a pharmacokinetic model for cockatiels (Nymphicus hollandicus) and Poicephalus parrots via comparison of the pharmacokinetics of a single intravenous injection of oxytetracycline hydrochlorideJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2005A. OSOFSKY The purpose of this study was to determine whether Japanese quail (Coturnix japonica) would serve as a pharmacokinetic animal model for two small companion parrots: cockatiels (Nymphicus hollandicus) and Poicephalus parrots. Oxytetracycline (OTC) was the pharmacologic agent chosen for this study as it is eliminated primarily by renal glomerular filtration and undergoes minimal metabolism. A single intravenous injection of 20 mg/kg oxytetracycline hydrochloride was administered to the three study groups and blood samples were obtained at 5, 10, 15, and 30 min post-OTC injection as well as 1, 2, 4, 8, 12 and 24 h post-OTC injection. Quantification of plasma OTC was accomplished using a standardized microbial inhibition assay. Naïve-pooled data (NPD) analysis of the plasma concentration,time profile of OTC best fit a two-compartment open model for all three avian species. Noncompartmental analysis of the mean data yielded the following parameters for quail, cockatiels and Poicephalus parrots respectively: ,z = 3.14, 4.57, 3.71 h; AUC = 38.9, 42.7, 49.6 ,g·h/mL; and Cl = 514, 468, 403 mL/h/kg. Based on the similarity of these pharmacokinetic parameters, it appears that quail could be used as a model species to predict the appropriate OTC dosing regimen for small psittacine birds. A bootstrap procedure was also applied to these sparse data sets for both compartmental and noncompartmental analysis. The bootstrap procedure allowed for the calculation of variability of parameters; however, the estimates of the parameters were very similar to those calculated using the NPD and the data mean values. [source] In vivo release of oxytetracycline from a biodegradable controlled-release gel injected subcutaneously in Japanese quail (Coturnix coturnix japonica)JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2003L. A. Tell A long-acting, biodegradable, controlled-release formulation of oxytetracycline (CR-OTC) was evaluated in 18 adult Japanese quail (Coturnix coturnix japonica) following a single subcutaneous (s.c.) injection. Prior to characterizing the release of oxytetracycline (OTC) from the CR-OTC, the pharmacokinetic parameters of intravenously (i.v.) administered OTC were determined. Concentrations of free OTC were measured using a bioassay. The plasma concentration,time profile of OTC after a single i.v. injection at 20 mg/kg was best fit to an open two-compartmental model, with the following pharmacokinetic parameters: area under the curve (AUC) = 36.72 mg · h/L, terminal elimination half-life = 2.34 h, clearance (Cl) = 0.545 L/kg/h. Plasma [OTC] was >1.0 ,g/mL for at least 4 h following i.v. injection. The CR-OTC gel was well tolerated at a dosage of 1500 mg/kg s.c. Plasma [OTC] rose to >1.0 ,g/mL within 24 h; it remained >1.0 ,g/mL for at least 10 days in all birds sampled at that time point (n = 9) and for at least 18 days in two of nine birds. Using a deconvolution technique, it was determined that approximately 54.8% of the administered OTC was released from the CR-OTC over the 45-day observation period. This long-acting, biodegradable controlled-release OTC formulation may have potential for the treatment of chlamydophila infections and other OTC-sensitive bacteria in Japanese quail, however further studies are necessary to determine its safety and clinical application. [source] Effects of altered plasma ,-1-acid glycoprotein levels on pharmacokinetics of some basic antibiotics in pigs: simulation analysisJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2001M. Kuroha Effects of altered plasma , -1-acid glycoprotein (AGP) levels on pharmacokinetic parameters of basic antimicrobials, erythromycin (EM), lincomycin (LM) and clindamycin (CM) were evaluated in pigs by simulation analysis. Intravenous (i.v.) injections of EM, LM and CM were performed to obtain pharmacokinetic parameters in healthy conditions. Binding parameters were obtained from an in vitro study using ultrafiltration. Simulation studies indicated that an increase of plasma AGP levels resulted in a decrease of both volume of distribution at steady state (Vdss) and total body clearance (Cltot) for all the drugs. Elimination rate constant for LM was almost unchanged by an increase of plasma AGP levels, whereas those for EM and CM were increased. Plasma concentration,time profiles at a high AGP level (often observed in pathophysiological conditions) were also simulated. All of the total plasma concentration,time profiles were different from those at normal AGP level. The differences were characterized by a higher initial concentration with faster or similar elimination. Unbound plasma concentration,time profile of LM was unaffected by AGP levels, whereas EM and CM were eliminated from plasma more rapidly at high AGP level. These results suggested that adjustment of dosage regimen of EM and CM is required in pathophysiological conditions, but that of LM is not required. [source] Increased blood,brain barrier permeability of morphine in a patient with severe brain lesions as determined by microdialysisACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2001R. Bouw Intracerebral microdialysis was utilised to obtain information regarding how morphine is transported across the blood,brain barrier (BBB). In a patient with a severe brain injury, we measured simultaneously unbound extracellular fluid (ECF) concentrations of morphine in human brain and in subcutaneous fat tissue, which were compared to morphine levels in arterial blood. This report shows an increase in morphine levels near the trauma site in the brain compared to uninjured brain tissue. The half-life of morphine in uninjured and injured brain tissue of 178 min and 169 min, respectively, were comparable but were longer than in blood (64 min) and adipose tissue (63 min). This indicates that morphine is retained in brain tissue for a longer time than what could be expected from the blood concentration,time profile. These results show the potential of the microdialysis technique in providing new information regarding the pharmacokinetics of drug in the human brain close to the trauma site and in macroscopically intact tissue. [source] Expectations Formation and Business Cycle Fluctuations: An Empirical Analysis of Actual and Expected Output in UK Manufacturing, 1975,1996OXFORD BULLETIN OF ECONOMICS & STATISTICS, Issue 4 2000Kevin Lee Direct measures of expectations, derived from survey data, are used in a Vector Autoregressive (VAR) model of actual and expected output in eight industries in the UK manufacturing sector. No evidence is found with which to reject rationality in the derived expectations series when measurement error is appropriately taken into account. The VAR analysis illustrates the importance of intersectoral interactions and business confidence in explaining the time profile of industrial outputs, examines the mechanisms by which shocks are propagated across sectors and over time and investigates the relative importance of sectoral and aggregate shocks of different types. [source] Carbon Taxation, Fuel Substitution and Welfare in AustraliaTHE AUSTRALIAN ECONOMIC REVIEW, Issue 1 2000John Creedy This paper examines the potential role for fuel substitution in electricity production in reducing carbon dioxide emissions over a ten-year time horizon. This is achieved by adding fuel substitution to output changes resulting from demand responses arising from a tax on carbon dioxide emissions. A time profile of adjustments is developed. The tax required for Australia to meet a 20 per cent reduction in emissions from 1993 levels is calculated and effects on inequality and social welfare are examined. The paper also examines the potential effect of a subsidy towards the use of low-emission fuels, financed from the carbon tax. A subsidy produces an improvement in emissions abatement and a lower tax required to reach the emissions target. [source] Reconstruction of an atmospheric tracer source using the principle of maximum entropy.THE QUARTERLY JOURNAL OF THE ROYAL METEOROLOGICAL SOCIETY, Issue 610 2005II: Applications Abstract A new method of performing the source inversion of a passive tracer at continental scale was proposed in Part I of this two-part paper. The method made use of prior information, general or specific (depending on the situation), to perform a better reconstruction using only the prior information and the field measurements of the tracer. In this paper the method is tested on its first applications. It is used on several test examples, using the meteorological conditions of the European Joint Research Centre ETEX-I campaign. The retrieval of a temporal profile of emission from a source whose location is known is studied before testing the method on a full reconstruction of the space,time profile of the source. Synthetic, but also real-measurement, inversions are tested, thanks to the extension of the formalism to noisy data. Copyright © 2005 Royal Meteorological Society [source] MEGX disposition in critically-ill trauma patients: subsequent assessments during the first week following traumaFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2002Federico Pea ABSTRACT The objective of this study was to evaluate MEGX disposition as a surrogate marker in assessing the influence that injury may exert on liver function during the first week after the traumatic event in young vs. elderly patients. The MEGX exposure over time was assessed at 0.25, 0.5, 1, 2, 4 and 6 h after the intravenous administration of a 1 mg/kg lidocaine test dose in 12 young and 7 elderly trauma patients on days1, 4 and 7 after a severe injury (Apache II score > 10). MEGX plasma concentration,time profiles were consistently different on day 1 in the elderly vs. young, consistent with a statistically significant lower rate of both lidocaine clearance and MEGX formation, and with a considerably longer MEGX elimination in the elderly than in the young. This suggests an impairment of liver blood flow as a result of splanchnic vasoconstriction occurring mainly in elderly trauma patients. A significant improvement in MEGX disposition occurred on days 4 and 7 vs. the day of trauma in most elderly, whereas minor changes were observed in the young. Multiple factors may account for these major changes in the elderly: the more severe status, the major sensitivity to the pathophysiologic changes induced by trauma, and also at least partially the ageing processes. Although referring to a limited number of observations, our findings on MEGX disposition suggest that liver function may be affected by the severity of injury, even if the influence of age should not be underestimated in these patients. [source] Validation of a thermal decomposition mechanism of formaldehyde by detection of CH2O and HCO behind shock wavesINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 3 2004Gernot Friedrichs The thermal decomposition of formaldehyde was investigated behind shock waves at temperatures between 1675 and 2080 K. Quantitative concentration time profiles of formaldehyde and formyl radicals were measured by means of sensitive 174 nm VUV absorption (CH2O) and 614 nm FM spectroscopy (HCO), respectively. The rate constant of the radical forming channel (1a), CH2O + M , HCO + H + M, of the unimolecular decomposition of formaldehyde in argon was measured at temperatures from 1675 to 2080 K at an average total pressure of 1.2 bar, k1a = 5.0 × 1015 exp(-308 kJ mol,1/RT) cm3 mol,1 s,1. The pressure dependence, the rate of the competing molecular channel (1b), CH2O + M , H2 + CO + M, and the branching fraction , = k1a/(kA1a + k1b) was characterized by a two-channel RRKM/master equation analysis. With channel (1b) being the main channel at low pressures, the branching fraction was found to switch from channel (1b) to channel (1a) at moderate pressures of 1,50 bar. Taking advantage of the results of two preceding publications, a decomposition mechanism with six reactions is recommended, which was validated by measured formyl radical profiles and numerous literature experimental observations. The mechanism is capable of a reliable prediction of almost all formaldehyde pyrolysis literature data, including CH2O, CO, and H atom measurements at temperatures of 1200,3200 K, with mixtures of 7 ppm to 5% formaldehyde, and pressures up to 15 bar. Some evidence was found for a self-reaction of two CH2O molecules. At high initial CH2O mole fractions the reverse of reaction (6), CH2OH + HCO , CH2O + CH2O becomes noticeable. The rate of the forward reaction was roughly measured to be k6 = 1.5 × 1013 cm3 mol,1 s,1. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 157,169 2004 [source] Modelling of air drying of fresh and blanched sweet potato slicesINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 2 2010Kolawole O. Falade Summary Effects of blanching, drying temperatures (50,80 °C) and thickness (5, 10 and 15 mm) on drying characteristics of sweet potato slices were investigated. Lewis, Henderson and Pabis, Modified Page and Page models were tested with the drying patterns. Page and Modified Page models best described the drying curves. Moisture ratio vs. drying time profiles of the models showed high correlation coefficient (R2 = 0.9864,0.9967), and low root mean squared error (RMSE = 0.0018,0.0130) and chi-squared (,2 = 3.446 × 10,6,1.03 × 10,2). Drying of sweet potato was predominantly in the falling rate period. The temperature dependence of the diffusion coefficient (Deff) was described by Arrhenius relationship. Deff increased with increasing thickness and air temperature. Deff of fresh and blanched sweet potato slices varied between 6.36 × 10,11,1.78 × 10,9 and 1.25 × 10,10,9.75 × 10,9 m2 s,1, respectively. Activation energy for moisture diffusion of the slices ranged between 11.1 and 30.4 kJ mol,1. [source] Kinetic analysis of oxytetracycline residues in Chinese mitten crab, Eriocheir sinensis, muscle following intramuscular administrationJOURNAL OF FISH DISEASES, Issue 8 2010Q Feng Abstract Crab culture is a very important economic industry in China. An epidemic of tremor disease of Chinese mitten crabs, Eriocheir sinensis, has become a serious problem in recent years. A spiroplasm has been proved to be the causative agent of this disease. Oxytetracycline (OTC) is used widely in aquaculture and was confirmed to be very effective against this pathogen. In this study, the distribution and depletion patterns of OTC in crab muscle were evaluated following single intramuscular doses of 2, 8 and 40 mg kg,1 body weight. OTC was detected with a validated HPLC method. Concentration,time profiles were well described by a three-compartment model with first-order absorption after a single dose of 8 and 40 mg kg,1. For comparison, a non-compartment model was employed. A withdrawal time of 48.29 and 55.92 days was suggested prior to consumption after receiving 8 and 40 mg kg,1. A recommended therapeutic dose of OTC in theory was calculated to be 36.37 mg kg,1. OTC was distributed well throughout the body. The elimination of OTC in muscle was slower compared with fish and other crustaceans. A dose of 40 mg kg,1 is suggested for practical use. [source] Peak capacity of ion mobility mass spectrometry: the utility of varying drift gas polarizability for the separation of tryptic peptidesJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 4 2004Brandon T. Ruotolo Abstract Ion mobility mass spectrometry (IM-MS) peptide mass mapping experiments were performed using a variety of drift gases (He, N2, Ar and CH4). The drift gases studied cover a range of polarizabilities ((0.2,2.6) × 10,24 cm3) and the peak capacities obtained for tryptic peptides in each gas are compared. Although the different gases exhibit similar peak capacities (5430 (Ar) to 7580 (N2)) in some cases separation selectivity presumably based on peptide conformers (or conformer populations), is observed. For example the drift time profiles observed for some tryptic peptide ions from aldolase (rabbit muscle) show a dependence on drift gas. The transmission of high-mass ions (m/z > 2000) is also influenced by increased scattering cross-section of the more massive drift gases. Consequently the practical peak capacity for IM-MS separation cannot be assumed to be solely a function of resolution and the ability of a gas to distribute signals in two-dimensional space; rather, peak capacity estimates must account for the transmission losses experienced for peptide ions as the drift gas mass increases. Copyright © 2004 John Wiley & Sons, Ltd. [source] Physiologically based predictions of the impact of inhibition of intestinal and hepatic metabolism on human pharmacokinetics of CYP3A substratesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2010Frederique Fenneteau Abstract The first objective of the present study was to predict the pharmacokinetics of selected CYP3A substrates administered at a single oral dose to human. The second objective was to predict pharmacokinetics of the selected drugs in presence of inhibitors of the intestinal and/or hepatic CYP3A activity. We developed a whole-body physiologically based pharmacokinetics (WB-PBPK) model accounting for presystemic elimination of midazolam (MDZ), alprazolam (APZ), triazolam (TRZ), and simvastatin (SMV). The model also accounted for concomitant administration of the above-mentioned drugs with CYP3A inhibitors, namely ketoconazole (KTZ), itraconazole (ITZ), diltiazem (DTZ), saquinavir (SQV), and a furanocoumarin contained in grape-fruit juice (GFJ), namely 6,,7,-dihydroxybergamottin (DHB). Model predictions were compared to published clinical data. An uncertainty analysis was performed to account for the variability and uncertainty of model parameters when predicting the model outcomes. We also briefly report on the results of our efforts to develop a global sensitivity analysis and its application to the current WB-PBPK model. Considering the current criterion for a successful prediction, judged satisfied once the clinical data are captured within the 5th and 95th percentiles of the predicted concentration,time profiles, a successful prediction has been obtained for a single oral administration of MDZ and SMV. For APZ and TRZ, however, a slight deviation toward the 95th percentile was observed especially for Cmax but, overall, the in vivo profiles were well captured by the PBPK model. Moreover, the impact of DHB-mediated inhibition on the extent of intestinal pre-systemic elimination of MDZ and SMV has been accurately predicted by the proposed PBPK model. For concomitant administrations of MDZ and ITZ, APZ and KTZ, as well as SMV and DTZ, the in vivo concentration,time profiles were accurately captured by the model. A slight deviation was observed for SMV when coadministered with ITZ, whereas more important deviations have been obtained between the model predictions and in vivo concentration,time profiles of MDZ coadministered with SQV. The same observation was made for TRZ when administered with KTZ. Most of the pharmacokinetic parameters predicted by the PBPK model were successfully predicted within a two-fold error range either in the absence or presence of metabolism-based inhibition. Overall, the present study demonstrated the ability of the PBPK model to predict DDI of CYP3A substrates with promising accuracy. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:486,514, 2010 [source] Pharmacokinetic prediction for intravenous ,-lactam antibiotics in pediatric patientsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2007Kenji Shimamura Abstract A method for predicting pharmacokinetics in pediatric patients for intravenous ,-lactam antibiotics is proposed. We focused on the allometric relationships of pharmacokinetic parameters with individual body weights (BW) in human including healthy adults and pediatric patients. Drug concentration data for 15 intravenous ,-lactam antibiotics were collected retrospectively from the published articles and the individual pharmacokinetic parameters were re-calculated. A mixed effect modeling (MEM) was applied for the allometric relationship for those ,-lactam antibiotics, and mean and variances of inter-drug variability for the allometric parameters and also variance for intra-drug (residual) variability were estimated. Then drug-specific allometric parameters were estimated by an empirical Bayesian method using the pharmacokinetic parameters for a drug only in healthy adults as observations, and finally the individual pharmacokinetic parameters in pediatric patients were predicted. The predictability of the method was evaluated by the leave-one-out method. We also demonstrated a method for simulating plasma concentration,time profiles in pediatric patients, and the predicted time,course curves generally coincided well with the actual plasma concentration data for the tested drugs. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3125,3139, 2007 [source] Stereoselective disposition of talinolol in manJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2002Michael Zschiesche Abstract The disposition of the ,-blocking drug talinolol is controlled by P-glycoprotein in man. Because talinolol is marketed as a racemate, we reevaluated the serum-concentration time profiles of talinolol of a previously published study with single intravenous (30 mg) and repeated oral talinolol (100 mg for 14 days) before and after comedication of rifampicin (600 mg per day for 9 days) in eight male healthy volunteers (age 22,26 years, body weight 67,84 kg) with respect to differences in the kinetic profiles of the two enantiomers S(,) talinolol and R(+) talinolol. Additionally, the metabolism of talinolol in human liver microsomes was examined. After oral administration, S(,) talinolol was slightly less absorbed and faster eliminated than R(+) talinolol. The absolute bioavailabilty of the R(+) enantiomer of talinolol was slightly but significantly higher than of its S(,) enantiomer. Coadministration of rifampicin further intensified this difference in the disposition of R(+) and S(,) talinolol (p,<,0.05). Formation of 4-trans hydroxytalinolol was the major metabolic pathway in human liver microsomes. All Clint values of S(,) were higher than of R(+) talinolol; 0.1 ,M ketoconazole inhibited the formation of all metabolites. In conclusion, the stereoselectivity of talinolol disposition is of minor importance, and most likely caused by presystemic biotransformation via CYP3A4. The less active R(+) talinolol might be suitable for phenotyping P-glycoprotein expression in man. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:303,311, 2002 [source] Applications of non-steady-state kinetics in physical organic chemistry: guidelines for the resolution of the kinetics of complex reaction mechanismsJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 9 2001Vernon D. Parker Abstract The resolution of the kinetics of the reversible consecutive second-order reaction mechanism involving the formation of a kinetically significant intermediate, which does not reach steady state before late in the first half-life, followed by an irreversible product-forming reaction is discussed. It is shown that an apparent second-order rate constant kapp and an extent of reaction,time profile are the only experimental data necessary for the evaluation of kf and kb (the forward and reverse rate constants) as well as kp (the microscopic rate constant for the product forming reaction). When the product-forming step involves the cleavage of a CH bond, for which there is a deuterium kinetic isotope effect on kp, the resolution of the kinetics is enhanced. In this case, the experimental data include two apparent rate constants ( and ) and two extent of reaction,time profiles, one for normal reactants and the other for isotopically substituted reactants. Under these circumstances, a unique highly resolved experimental to theoretical data fit is found that results in the evaluation of all four microscopic rate constants: and . An alternative, when a kinetic isotope effect is not involved, is to fit the extent of reaction,time profiles for two or more concentrations of reactants concurrently. This procedure results in the resolution of the three microscopic rate constants for the reaction. Copyright © 2001 John Wiley & Sons, Ltd. [source] Estimation of absolute oral bioavailability of moxidectin in dogs using a semi-simultaneous method: influence of lipid co-administrationJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2007E. LALLEMAND Moxidectin is a long-acting anthelmintic drug for which little is known about its kinetic behaviour in dogs and its oral absolute bioavailability has never been reported. We studied the pharmacokinetics of moxidectin in dogs, with a special emphasis on oral bioavailability and the influence of lipid co-administration, by using a semi-simultaneous method of administration. Ten Beagle dogs were dosed orally and then intravenously (i.v.) with 0.2 mg/kg moxidectin. The oral application was conducted with or without corn oil co-administration. Moxidectin concentration,time profiles in plasma were analysed using a compartmental modelling approach, designed to fit the oral and i.v. kinetic disposition curves simultaneously. In contrast to what happens in other species, our study indicates that the bioavailability of orally given moxidectin in dogs is nearly total (90.2 ± 7.4%), and is not enhanced by lipid co-administration. The clearance, the volume of distribution, the mean residence time and the terminal half-life were similar to what was already described for other species. Finally our trial suggests that the body condition (degree of obesity) is likely to be a major determinant of moxidectin kinetics in dogs because of its modulation of the volume of distribution that indirectly controls the terminal half-life of the drug. [source] Simulation of concentration,time profiles of benzyl-penicillin, enrofloxacin and dihydrostreptomycin in tissue cages in calvesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2002B. Bengtsson First page of article [source] Effects of altered plasma ,-1-acid glycoprotein levels on pharmacokinetics of some basic antibiotics in pigs: simulation analysisJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2001M. Kuroha Effects of altered plasma , -1-acid glycoprotein (AGP) levels on pharmacokinetic parameters of basic antimicrobials, erythromycin (EM), lincomycin (LM) and clindamycin (CM) were evaluated in pigs by simulation analysis. Intravenous (i.v.) injections of EM, LM and CM were performed to obtain pharmacokinetic parameters in healthy conditions. Binding parameters were obtained from an in vitro study using ultrafiltration. Simulation studies indicated that an increase of plasma AGP levels resulted in a decrease of both volume of distribution at steady state (Vdss) and total body clearance (Cltot) for all the drugs. Elimination rate constant for LM was almost unchanged by an increase of plasma AGP levels, whereas those for EM and CM were increased. Plasma concentration,time profiles at a high AGP level (often observed in pathophysiological conditions) were also simulated. All of the total plasma concentration,time profiles were different from those at normal AGP level. The differences were characterized by a higher initial concentration with faster or similar elimination. Unbound plasma concentration,time profile of LM was unaffected by AGP levels, whereas EM and CM were eliminated from plasma more rapidly at high AGP level. These results suggested that adjustment of dosage regimen of EM and CM is required in pathophysiological conditions, but that of LM is not required. [source] Pharmacokinetics of amoxycillin in normal horses and horses with experimental arthritisJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2001J. O. Errecalde The serum and synovial pharmacokinetics of amoxycillin (AMX) were studied after i.v. administration at a dosage of 40 mg/kg to normal horses and horses with induced aseptic carpal arthritis. The best estimates of serum and synovial pharmacokinetic parameters were calculated by mono or bivariable non-linear regression analysis. A biexponential equation was used to describe the concentration vs. time profiles in both normal and arthritic horses. There were no serum kinetic differences between normal and arthritic horses. There were, however, major synovial kinetic changes between these groups. The rate of penetration from serum to synovial fluid was larger in arthritic animals, indicating better penetration in this case. On the other hand, the rate of disappearance from synovial fluid was larger in normal horses, indicating more persistence of the drug in the diseased joint. Synovial AMX availability increased from 21% in normal horses to 79% in arthritic horses. These findings support the use of AMX for the treatment of infectious synovial joint disease produced by susceptible organisms in horses. [source] Study of Laser-Induced Photopolymerizations by Optical PyrometryMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 15 2004Patrick Lin Abstract Summary: Studies of the 355 nm laser induced free radical and cationic photopolymerization reactions of mono- and multifunctional monomers were conducted. These investigations were carried out with the aid of a specially constructed optical pyrometry instrument that provides rapid, reproducible temperature versus time profiles for these fast photopolymerization reactions. Using this technique, the effects of various reaction parameters and monomer structures on the rate and extent of the photopolymerization reactions were examined. Optical pyrometry instrument for the monitoring of laser-induced photopolymerizations. [source] | |||||||||||||||||||||||||