Home About us Contact
|
Home About us Contact | ||
|
|
||
Concentration Data (concentration + data)
Selected AbstractsTHE IMPORTANCE OF THE ,BEST RELATIVE FIT FACTOR' WHEN EVALUATING ELEMENTAL CONCENTRATION DATA OF POTTERY DEMONSTRATED WITH MYCENAEAN SHERDS FROM SINDA, CYPRUSARCHAEOMETRY, Issue 2 2007H. MOMMSEN Neutron activation analysis of pottery was established at Bonn in 1983 and has since become one of the primary archaeometry-based analytical techniques at the facility. A brief history of the laboratory and a discussion of the best relative fit procedure for pottery is provided. When comparing concentration data for pottery, a best relative fit should always be considered. This mathematical procedure generally results in ,sharper' concentration patterns and improves the separability of chemically not very different compositional groups. This is demonstrated for a set of 30 Late Cypriot (Myc. IIIC1) pottery samples from Sinda, Cyprus, which allow formation of a good reference pattern for this site. Applying factors in the range of 0.82,1.43, a number of samples from Egypt and Palestine can be assigned with high probability to a Cypriot origin. [source] Technical basis for narcotic chemicals and polycyclic aromatic hydrocarbon criteria.ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2000Abstract A method is presented for developing water quality criteria (WQC) for type I narcotic chemicals in general and PAHs in particular. The criteria can be applied to any individual or mixture of narcotic chemicals using only the chemical's octanol-water partition coefficient KOW. It is derived from a database of LC50s comprising 156 chemicals and 33 species, including fish, amphibians, arthropods, mollusks, polychaetes, coelenterates, and protozoans. A target lipid model is proposed that accounts for variations in toxicity due to differing species sensitivities and chemical differences. The model is based on the idea that a target lipid is the site of action in the organism. Further, it is assumed that target lipid has the same lipid-octanol linear free energy relationship for all species. This implies that the slope of the log(LC50),log(KOW) relationship is the same for all species. However, individual species may have varying target lipid body burdens that cause toxicity. The target lipid LC50 body burdens derived from concentration data in the water only are compared to measured total lipid LC50 body burdens for five species. They are essentially equal, indicating that the target lipid concentration is equal to the total extracted lipid concentration. The precise relationship between partitioning in target lipid and octanol is established. The species-specific body burdens are used to determine the WQC final acute value, i.e., the 95-percentile level of protection. An acute-to-chronic ratio is used to compute the body burden corresponding to the WQC final chronic value, which is the procedure used to derive the U.S. Environmental Protection Agency water quality criteria. The criteria are expressed either as dissolved concentrations in the water column or as tissue concentrations. [source] Predicting intra-urban variation in air pollution concentrations with complex spatio-temporal dependencies,ENVIRONMETRICS, Issue 6 2010Adam A. Szpiro Abstract We describe a methodology for assigning individual estimates of long-term average air pollution concentrations that accounts for a complex spatio-temporal correlation structure and can accommodate spatio-temporally misaligned observations. This methodology has been developed as part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), a prospective cohort study funded by the US EPA to investigate the relationship between chronic exposure to air pollution and cardiovascular disease. Our hierarchical model decomposes the space--time field into a "mean" that includes dependence on covariates and spatially varying seasonal and long-term trends and a "residual" that accounts for spatially correlated deviations from the mean model. The model accommodates complex spatio-temporal patterns by characterizing the temporal trend at each location as a linear combination of empirically derived temporal basis functions, and embedding the spatial fields of coefficients for the basis functions in separate linear regression models with spatially correlated residuals (universal kriging). This approach allows us to implement a scalable single-stage estimation procedure that easily accommodates a significant number of missing observations at some monitoring locations. We apply the model to predict long-term average concentrations of oxides of nitrogen (NOx) from 2005 to 2007 in the Los Angeles area, based on data from 18 EPA Air Quality System regulatory monitors. The cross-validated IR2 is 0.67. The MESA Air study is also collecting additional concentration data as part of a supplementary monitoring campaign. We describe the sampling plan and demonstrate in a simulation study that the additional data will contribute to improved predictions of long-term average concentrations. Copyright © 2009 John Wiley & Sons, Ltd. [source] Generalized Birnbaum-Saunders distributions applied to air pollutant concentrationENVIRONMETRICS, Issue 3 2008Víctor Leiva Abstract The generalized Birnbaum-Saunders (GBS) distribution is a new class of positively skewed models with lighter and heavier tails than the traditional Birnbaum-Saunders (BS) distribution, which is largely applied to study lifetimes. However, the theoretical argument and the interesting properties of the GBS model have made its application possible beyond the lifetime analysis. The aim of this paper is to present the GBS distribution as a useful model for describing pollution data and deriving its positive and negative moments. Based on these moments, we develop estimation and goodness-of-fit methods. Also, some properties of the proposed estimators useful for developing asymptotic inference are presented. Finally, an application with real data from Environmental Sciences is given to illustrate the methodology developed. This example shows that the empirical fit of the GBS distribution to the data is very good. Thus, the GBS model is appropriate for describing air pollutant concentration data, which produces better results than the lognormal model when the administrative target is determined for abating air pollution. Copyright © 2007 John Wiley & Sons, Ltd. [source] Distribution of larval fishes among water masses in Onslow Bay, North Carolina: implications for cross-shelf exchangeFISHERIES OCEANOGRAPHY, Issue 6 2005A. M. QUATTRINI Abstract The Gulf Stream (GS) is a major oceanographic feature with potential to influence the recruitment of larval fishes to continental shelf habitats in the southeastern United States. To test the hypothesis that the GS is a source of certain larval fishes to Onslow Bay, North Carolina, we (i) classified water masses as shelf, GS, GS front (GSF), or GS/shelf mixture (GS/S); (ii) compared larval fish assemblages and concentrations among these water masses; and (iii) compared length,frequency distributions and length,concentration relationships of indicator and commercially important taxa among water masses. A total of 21,222 larvae were collected with bongo and neuston nets from April 2000 to December 2001. Non-metric multidimensional scaling analyses revealed distinct larval assemblages associated with different water masses. For bongo catches, bothids were abundant in all water masses, gobiids, callionymids, and labrids were abundant in shelf waters, and myctophids and scombrids were abundant in the GS. For neuston catches, carangids dominated in GS/S, GSF, and GS waters, whereas triglids were abundant in shelf water. Larval concentrations in neuston catches were lower in shelf waters and higher in GS and GSF waters. Concentrations of most taxa in bongo catches were low in the GS and higher in shelf waters. We used trends in myctophid (offshore/GS) and gobiid (shelf) length,concentration data as indicators of the sources of commercially important serranids. Length distributions and concentrations of larval indicator taxa suggested local, shelf spawning, and transport of larvae from offshore. [source] Neutron Activation Analysis Applied to the Determination of Heavy Metals and Other Trace Elements in Sediments from Sepetiba Bay (RJ), BrazilGEOSTANDARDS & GEOANALYTICAL RESEARCH, Issue 2-3 2001Fŕbio Pellegatti analyse par activation neutronique; métaux lourds; éléments en traces; sédiments marins In this work, instrumental neutron activation analysis (INAA) was applied to the determination of the elements As, Ba, Br, Ce, Co, Cr, Cs, Eu, Fe, Hf, La, Lu, Nd, Rb, Sc, Sm, Ta, Tb, Th, U, Yb, Zn in twenty eight bottom sediment samples from Sepetiba Bay, Rio de Janeiro, Brazil. With the concentration data obtained, contour maps were prepared, by using Kriging method, to show the spatial distribution of the studied elements in the Bay. The elements Co, Cr, Cs, Fe, Sc, Ta and Zn showed similar behaviour in the sediments, with higher concentrations along the northern coast of the bay, where the fluvial water inputs are concentrated. The distribution of U, rare earth elements and Ba in the Bay indicates that these elements are not deposited as contaminants. Dans ce travail, les éléments suivants, As, Ba, Br, Ce, Co, Cr, Cs, Eu, Fe, Hf, La Lu, Nd, Rb, Sc, Sm, Ta, Tb, Th, U, Yb et Zn ont été analysés par activation neutronique instrumentale dans vingt huit sédiments de fond de la baie de Sepetiba, Rio de Janeiro, Brésil. Par krigeage et ŕ partir des concentrations obtenues, nous avons établi des cartes de la répartition spatiale des éléments étudiés dans la baie. Co, Cr, Cs, Fe, Sc, Ta et Zn ont des comportements similaires dans les sédiments, avec des concentrations plus importantes le long de la côte nord de la baie, oú les apports en eau fluviale sont concentrés. La distribution en U, Terres Rares et Ba indique que ces éléments ne sont pas déposés comme polluants dans la baie. [source] Use of Observations below Detection Limit for Model CalibrationGROUND WATER, Issue 2 2009Michael LeFrancois Censored (nondetect) values occur when chemical concentrations in water samples are near or below the level that can be measured by an analysis method. It is common to either delete or substitute values for nondetect observations for use in model calibration, but this practice can bias the estimated parameter values and the model predictions. A more realistic representation of the system is obtained from the calibration if we include such observations in a manner reflecting that we know only the value is below the detection limit. Consequently, we propose use of the censored-residual approach to including nondetect values as observations for calibration. In this approach, residuals are calculated as the detection limit minus the simulated value when the simulated value exceeds the detection limit, and the residual is assigned a value of zero when the simulated value is below the detection limit. The new censored-residual approach is particularly advantageous when calibrating transport models to low concentration data. [source] Stochastic Cost Optimization of Multistrategy DNAPL Site RemediationGROUND WATER MONITORING & REMEDIATION, Issue 3 2010Jack Parker This paper investigates numerical optimization of dense nonaqueous phase liquid (DNAPL) site remediation design considering effects of prediction and measurement uncertainty. Results are presented for a hypothetical problem involving remediation using thermal source reduction (TSR) and bioremediation with electron donor (ED) injection. Pump-and-treat is utilized as a backup measure if compliance criteria are not met. Remediation system design variables are optimized to minimize expected net present value (ENPV) cost. Adaptive criteria are assumed for real-time control of TSR and ED duration. Source zone dissolved concentration data enabled more reliable and lower cost operation of TSR than soil concentration data, but using both soil and dissolved data improved results sufficiently to more than offset the additional cost. Decisions to terminate remediation and monitoring or to initiate pump-and-treat are complicated by measurement noise. Simultaneous optimization of monitoring frequency, averaging period, and lookback periods to confirm decisions, in addition to remediation design variables, reduced ENPV cost. Results indicate that remediation design under conditions of uncertainty is affected by subtle interactions and tradeoffs between design variables, compliance rules, site characteristics, and uncertainty in model predictions and monitoring data. Optimized designs yielded cost savings of up to approximately 50% compared with a nonoptimized design based on common engineering practices. Significant improvements in accuracy and reductions in cost were achieved by recalibrating the model to data collected during remediation and re-optimizing design variables. Repeating this process periodically is advisable to minimize total costs and maximize reliability. [source] Permanganate Treatment of an Emplaced DNAPL SourceGROUND WATER MONITORING & REMEDIATION, Issue 4 2007Neil R. Thomson In situ chemical oxidation (ISCO) using permanganate is one of the few promising technologies that have recently appeared with the capability of aggressively removing mass from nonaqueous phase liquid (NAPL) source zones. While NAPL mass in regions of the treatment zone where delivery is dominated by advection can be removed rather quickly, the rate of mass removal from stagnant zones is diffusion controlled. This gives rise to partial mass removal and a concomitant reduction in the NAPL mass, downgradient ground water concentrations, and the dissolution rate associated with the source zone. Therefore, monitoring the performance of a permanganate ISCO treatment system is important to maintain the desired efficiency and to establish a treatment end point. In this paper, we illustrate the use of various monitoring approaches to assess the performance of a pilot-scale investigation that involved treatment of a multicomponent NAPL residual source zone with permanganate using a ground water recirculation system for 485 d. Ongoing treatment performance was assessed using permanganate and chloride concentration data obtained from extraction wells, 98 piezometers located approximately 1 m downgradient from the source, and ground water profiling. At the completion of treatment, 23 intact soil cores were extracted from the source zone and used to determine the remaining NAPL mass and manganese deposition. Based on the data collected, more than 99% of the initial NAPL mass was removed during treatment; however, remnant NAPL was sufficient to generate a small but measurable dissolved phase trichloroethene (TCE) and perchloroethene (PCE) plume. As a result of treatment, the ambient-gradient discharge rates were reduced by 99% for TCE and 89% for PCE relative to baseline conditions. The lack of complete source zone oxidation was presumed to be the result of dissolution fingers, which channeled the permanganate solution through the source zone preventing direct contact with the NAPL and giving rise to diffusion-limited mass removal. [source] A review of the suspended sediment budget at the confluence of the Paraná and Paraguay RiversHYDROLOGICAL PROCESSES, Issue 22 2009Mario L. Amsler Abstract In this paper, the sediment budget at the confluence of the Paraná,Paraguay Rivers is updated on the basis of new suspended sediment concentration data, obtained during the 1990s at carefully located cross-sections, after the construction of several large reservoirs. With these data, it was possible to estimate that the suspended sediment load transported by the Upper Paraná River had decreased by 60% due to the influence of the dams. This decrease occurred in spite of the influence of climate change across the Upper Paraná and Paraguay basin, which increased the precipitation and surface runoff. As a consequence of these anthropogenic and natural processes, the Bermejo River (the main source of wash load to the system) accounts for an increasing proportion of the sediment transport along the middle and lower reaches of the Paraná River. The Paraná River currently transports about 120 × 106 t year,1 of wash load, with nearly 90% of this being supplied by the Bermejo. The contribution from the Bermejo is now about 35% larger than its contribution during the 1970s, when it accounted for approximately 60% of the sediment load of the Paraná River. These changes that have occurred over the last 30 years have enhanced the natural asymmetrical distribution of solid and water discharges in the Paraná River basin. Copyright © 2009 John Wiley & Sons, Ltd. [source] Baseflow and peakflow chemical responses to experimental applications of ammonium sulphate to forested watersheds in north-central West Virginia, USA,HYDROLOGICAL PROCESSES, Issue 12 2002Pamela J. Edwards Abstract Stream water was analysed to determine how induced watershed acidification changed the chemistry of peakflow and baseflow and to compare the relative timing of these changes. Two watersheds in north-central West Virginia, WS3 and WS9, were subjected to three applications of ammonium sulphate fertilizer per year to induce acidification. A third watershed, WS4, was the control. Samples were collected for 8 years from WS9 and for 9 years from WS3. Prior to analyses, concentration data were flow adjusted, and the influence of natural background changes was removed by accounting for the chemical responses measured from WS4. This yielded residual values that were evaluated using robust locally weighted regression and Mann,Kendall tests. On WS3, analyte responses during baseflow and peakflow were similar, although peakflow responses occurred soon after the first treatment whereas baseflow responses lagged 1,2 years. This lag in baseflow responses corresponded well with the mean transit time of baseflow on WS3. Anion adsorption on WS3 apparently delayed increases in SO4 leaching, but resulted in enhanced early leaching losses of Cl and NO3. Leaching of Ca and Mg was strongly tied, both by timing and stoichiometrically, to NO3 and SO4 leaching. F -factors for WS3 baseflow and peakflow indicated that the catchment was insensitive to acid neutralizing capacity reductions both before and during treatment, although NO3 played a large role in reducing the treatment period F -factor. By contrast, the addition of fertilizer to WS9 created an acid sensitive system in both baseflow and peakflow. On WS9, baseflow and peakflow responses also were similar to each other, but there was no time lag after treatment for baseflow. Changes in concentrations generally were not as great on WS9 as on WS3, and several ions showed no significant changes, particularly for peakflow. The lesser response to treatment on WS9 is attributed to the past abusive farming and site preparation before larch planting that resulted in poor soil fertility, erosion, and consequently, physical and chemical similarities between upper and lower soil layers. Even with fertilizer-induced NO3 and SO4 leaching increases, base cations were in low supplies and, therefore, unavailable to leach via charge pairing. The absence of a time lag in treatment responses for WS9 baseflow indicates that it has substantially different flow paths than WS3. The different hydrologies on these nearby watersheds illustrates the importance of understanding watershed hydrology when establishing a monitoring programme to detect ecosystem change. Published in 2002 by John Wiley & Sons, Ltd. [source] MULTIVARIATE ANALYSIS FOR CLASSIFICATION OF COMMERCIAL GRAPEFRUIT JUICE PRODUCTS BY VOLATILE CONSTITUTESJOURNAL OF FOOD QUALITY, Issue 3 2000JORGE A. PINO ABSTRACT Isolation of volatile constituents from fresh and processed grapefruit juice by a simple technique afforded up to 20 components in each juice type. Many of these constituents are known to contribute to grapefruit juice flavor. Multivariate analysis utilizing the concentration data of twelve constituents allowed classification of the juice samples according to processing conditions. The classification corresponded to expected flavor quality. [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] Single-dose study to compare the pharmacokinetics of HFA flunisolide and CFC flunisolideJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2002Arno Nolting Abstract The hydrofluoroalkane (HFA) formulation of the inhaled corticosteroid flunisolide is a modification of the original chlorofluorocarbon (CFC) formulation. HFA flunisolide replaces CFC with an HFA propellant and uses a built-in spacer in its pressurized metered-dose inhaler. The average HFA flunisolide particle size is 1.2 ,m compared with 3.8 ,m for the CFC formulation. The smaller particle size improves lung targeting, allowing a reduction in the HFA flunisolide dose relative to CFC flunisolide while maintaining comparable efficacy. In a study of 12 healthy men, pharmacokinetic parameters were determined after single doses of 1000 ,g CFC flunisolide delivered without a spacer, 340 ,g HFA flunisolide delivered through a spacer, and 516 ,g HFA flunisolide delivered without a spacer. A standard noncompartmental analysis of the concentration data was performed and mean (±,S.D.) pharmacokinetic values were reported. Peak plasma concentrations (observed Cmax) were similar for the three treatments. Area under the curve up to the time corresponding to the last measurable concentration (AUC0,tlast) was similar for the CFC and HFA flunisolide, plus spacer groups (4.4,±,1.6 ng·h/mL and 5.0,±,4.2 ng·h/mL, respectively); however, AUC0,tlast for the HFA flunisolide without spacer group was comparatively lower than for the CFC group (3.5,±,1.6 ng·h/mL). Observed Cmax and AUC0,tlast for 6,-OH flunisolide, the first-pass metabolite of flunisolide and an indicator of oropharyngeal deposition, were significantly higher in the CFC flunisolide group than in either HFA flunisolide group. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:424,432, 2002 [source] Thermodynamic Modeling of Polymer Solution InterfaceMACROMOLECULAR THEORY AND SIMULATIONS, Issue 2 2009Majid Ghiass Abstract A new method is presented to characterize the interfacial concentration field and interfacial tension between equilibrium polymer solution phases, using readily accessible equilibrium concentration data. The new method is tested and validated using experimental data from different polystyrene solutions and it consists of i) calculation of a universal expression for the concentration gradient coefficient based on the Cahn-Hilliard model and the Wolf interfacial tension master equation, and ii) development of a highly accurate algebraic function (Kappa distribution) that, for a given equilibrium polymer concentration set, yields the essentially exact interfacial profile predicted by the classical gradient theory for polymer solutions. [source] Comparison of atmospheric transport calculations over complex terrain using a mobile profiling system and rawinsondesMETEOROLOGICAL APPLICATIONS, Issue 4 2000Robert M Cox A comparison of atmospheric transport and dispersion calculations over complex terrain was investigated using a mobile profiling system (MPS) versus standard meteorological balloons. Meteorological and sulfur hexafluoride (SF6) concentration data were collected and used to evaluate the performance of a transport and diffusion model coupled with a mass consistency wind field model. Meteorological data were collected throughout April 1995, and parts of August 1995. Both meteorological and concentration data were measured in December 1995. Once the models were validated, the comparison of performance with different upper-air data were accomplished. The models used included the SCIPUFF (Second-order Closure Integrated Puff) transport and diffusion model and the MINERVE mass consistency wind model. Evaluation of the models was focused primarily on their effectiveness as a short-term (one to four hours) predictive tool. These studies showed how the combination of weather and transport models could be used to help direct emergency response following a hazardous material release. The models were used in tandem to direct the deployment of mobile sensors intended to intercept and measure tracer clouds. The MINERVE model was validated for the specific terrain of interest using April 1995 data. The capability of SCIPUFF driven by realistic three-dimensional wind fields generated by MINERVE is demonstrated using data collected in December 1995. Copyright © 2000 Royal Meteorological Society [source] Triad case study: Marine Corps Base Camp PendletonREMEDIATION, Issue 1 2004Adrianne V. Saboya The U.S. Navy Public Works Center (PWC) Environmental Department, San Diego, California, is home to the Navy West Coast Site Characterization and Analysis Penetrometer System (SCAPS). SCAPS has been extensively used at several Navy sites since 1995 to provide real-time, high-density data sets. The U.S. Environmental Protection Agency's Triad approach provided an ideal framework for optimizing the use of the Navy SCAPS during a volatile organic compound (VOC) source investigation at Installation Restoration Site 1114 at Marine Corps Base Camp Pendleton. All three elements of Triad,systematic planning, dynamic work strategy, and use of real-time measurement tools,were implemented to manage decision uncertainty and expedite the site management process. The investigation was conducted using the Navy SCAPS, outfitted with a cone penetrometer, membrane interface probe, and a direct sampling ion trap mass spectrometry detector, which allowed for real- time collection of over 690 feet of continuous lithologic information and VOC concentration data. These data were used collaboratively with 24-hour turnaround US EPA 8260B VOC groundwater results from temporary direct- push wells to support the conclusion of a limited source area. Implementation of the Triad approach for this investigation provided an expedited high-density data set and a refined conceptual site model (CSM) in real time that resulted in cost savings estimated at $2.5M and reduction of the site characterization and cleanup schedule by approximately three years. This project demonstrates how the US EPA's Triad approach can be applied to streamline the site characterization and cleanup process while appropriately managing decision uncertainty in support of defensible site decisions. © 2004 Wiley Periodicals, Inc. [source] THE IMPORTANCE OF THE ,BEST RELATIVE FIT FACTOR' WHEN EVALUATING ELEMENTAL CONCENTRATION DATA OF POTTERY DEMONSTRATED WITH MYCENAEAN SHERDS FROM SINDA, CYPRUSARCHAEOMETRY, Issue 2 2007H. MOMMSEN Neutron activation analysis of pottery was established at Bonn in 1983 and has since become one of the primary archaeometry-based analytical techniques at the facility. A brief history of the laboratory and a discussion of the best relative fit procedure for pottery is provided. When comparing concentration data for pottery, a best relative fit should always be considered. This mathematical procedure generally results in ,sharper' concentration patterns and improves the separability of chemically not very different compositional groups. This is demonstrated for a set of 30 Late Cypriot (Myc. IIIC1) pottery samples from Sinda, Cyprus, which allow formation of a good reference pattern for this site. Applying factors in the range of 0.82,1.43, a number of samples from Egypt and Palestine can be assigned with high probability to a Cypriot origin. [source] Validation of Microdialysis Sampling for Oral Availability Studies by Means of a New Ganciclovir ProdrugBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2002Karin Lindén Three different techniques were used in the study; microdialysis, blood and urinesampling. The oral uptake (11±2%) and the urinary recovery (106±5%) were determined. Animals given ganciclovir subcutaneously were subject either to microdialysis and blood sampling or to microdialysis alone. There was no significant difference between microdialysis and blood sampling in terms of blood concentration data, CL, Vd, half-life or AUC by means of Student's t-test. The oral bioavailability of the prodrug was 40±7% estimated from microdialysis sampling data and 48±4% estimated from urine sampling data. It is concluded that microdialysis is a valid method to use in pharmacokinetic studies of oral availability as well as for basic pharmacokinetic parameter estimation. [source] Pharmacokinetic modelling of blood,brain barrier transport of escitalopram in ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2007Christoffer Bundgaard Abstract This study examined the pharmacokinetics and distribution of escitalopram in the brain extracellular fluid in rats by the concurrent use of intracerebral microdialysis and serial blood sampling. Following three constant intravenous infusions, drug concentrations in the hippocampus and plasma were monitored for 6 h. To estimate the integrated pharmacokinetics and intercompartmental transport parameters, including blood,brain barrier (BBB) transport over the entire dose range, unbound brain and plasma escitalopram concentration data from all doses were simultaneously analysed using compartmental modelling. The pharmacokinetic analysis revealed that systemic clearance decreased as a function of dose, which was incorporated in the integrated model. Escitalopram was rapidly and extensively transported across the BBB and distributed into the brain extracellular fluid. The modelling resulted in an estimated influx clearance into the brain of 535 µl/min/g brain, resulting in an unbound brain-to-plasma AUC ratio of 0.8 independent of escitalopram dose. The model may be applied for preclinical evaluations or predictions of escitalopram concentration-time courses in plasma as well as at the target site in the CNS for various dosing scenarios. In addition, this modelling approach may also be valuable for studying BBB transport characteristics for other psychotropic agents. Copyright © 2007 John Wiley & Sons, Ltd. [source] Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapyBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2009Kunihiro Suzuki WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Co-administration of proton pump inhibitors (PPIs) increases plasma methotrexate (MTX) concentration in cancer patients receiving high-dose MTX (HDMTX) therapy. , There is controversy as to whether or not co-administration of PPIs affects plasma MTX elimination in HDMTX therapy. , Inhibitory activity of PPIs on breast cancer resistance protein (BCRP) is a possible mechanism for the drug interaction between MTX and PPIs. WHAT THIS STUDY ADDS , Co-administration of a PPI (omeprazole, lansoprazole, or rabeprazole) was more frequently observed in the delayed MTX elimination group than in the normal MTX elimination group. , Multiple logistic regression analysis with adjustment for significant covariates revealed that PPI co-administration was a significant risk factor for delayed plasma MTX elimination. , The half-maximal inhibitory concentration of each PPI in inhibiting BCRP function was much higher than the therapeutic unbound concentration in the plasma. AIM To assess whether or not co-administration of proton pump inhibitors (PPIs) is a risk factor for delayed elimination of plasma methotrexate (MTX) in high-dose MTX (HDMTX) therapy for malignant diseases. METHODS To assess the effects of PPI co-administration on elimination of plasma MTX, we examined plasma MTX concentration data on 171 cycles of HDMTX therapy performed in 74 patients. We performed multiple logistic regression analysis to evaluate PPI co-administration as a risk factor. Inhibitory potencies of omeprazole, lansoprazole, rabeprazole and pantoprazole on MTX transport via breast cancer resistance protein (BCRP, ABCG2) were also investigated in an in vitro study using membrane vesicles expressing human BCRP. RESULTS We identified co-administration of PPIs as a risk factor for delayed elimination (odds ratio 2.65, 95% confidence interval 1.03, 6.82) as well as renal and liver dysfunction. All four PPIs inhibited BCRP-mediated transport of MTX, with half-maximal inhibitory concentrations of 5.5,17.6 µM , considerably higher than the unbound plasma concentrations of the PPIs. CONCLUSIONS Our results support previous findings suggesting that PPI co-administration is associated with delayed elimination of plasma MTX in patients with HDMTX therapy. This drug interaction, however, cannot be explained solely by the inhibitory effects of PPIs on BCRP-mediated MTX transport. [source] Population pharmacokinetic modelling of aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2008Jung-Ryul Kim WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Almost all reported studies have investigated the pharmacokinetics of aripiprazole in healthy volunteers. , The pharmacokinetics of dehydroaripiprazole have not been identified in a combined model with aripiprazole. WHAT THIS STUDY ADDS , The data on aripiprazole and dehydroaripiprazole in psychiatric patients were modelled jointly using a population approach. , The apparent clearance of aripiprazole in cytochrome P450 (CYP) 2D6 intermediate metabolizers (IM) was approximately 60% of that in CYP2D6 extensive metabolizers (EM) having two functional alleles, but the exposure to dehydroaripiprazole in CYP2D6 IM was similar to that in EM. AIMS The aims of this study were to develop a combined population pharmacokinetic model for both aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients and to identify to what extent the genetic polymorphisms of cytochrome P450 (CYP) enzymes contribute to the variability in pharmacokinetics (PK). METHODS A population pharmacokinetic analysis was performed using NONMEM software based on 141 plasma concentrations at steady state from 80 patients receiving multiple oral doses of aripiprazole (10,30 mg day,1). RESULTS A one-compartment model with first-order kinetics for aripiprazole and dehydroaripiprazole each was developed to describe simultaneously the concentration data. The absorption rate constant was fixed to 1.06 h,1. The typical value of apparent distribution volume of aripiprazole was estimated to be 192 l. Covariate analysis showed that CYP2D6 genetic polymorphisms significantly influenced the apparent clearance of aripiprazole (CL/F), reducing the interindividual variability on CL/F from 37.8% CV (coefficient of variation) to 30.5%. The CL/F in the CYP2D6 IMs was approximately 60% of that in CYP2D6 EMs having two functional alleles. Based on the CYP2D6 genotype, the metabolic ratios were calculated at 0.20,0.34. However, the plasma concentration : dose ratios of dehydroaripiprazole were not different across the CYP2D6 genotype. CONCLUSIONS This population pharmacokinetic model provided an adequate fit to the data for both aripiprazole and dehydroaripiprazole in psychiatric patients. The usefulness of CYP genotyping as an aid to select the starting dose should be further investigated. [source] Dose selection and population pharmacokinetics of PEG-Intron in patients with chronic myelogenous leukaemiaBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2007Samir Gupta Aims To assess the dose selection using population pharmacokinetics of Pegylated Intron-,2b (PEG-Intron) in patients with chronic myelogenous leukaemia (CML). Methods PEG-Intron 3,6 µg kg,1 was administered subcutaneously once a week and blood samples were collected up to 48 weeks of treatment. A total of 624 samples collected from 137 patients were included in the analysis. Nonlinear mixed-effects modelling was used to analyse the sparsely sampled concentration data from a clinical efficacy trial. Covariates in the analysis included weight, sex, age, race, serum creatinine and estimated creatinine clearance (CLcr). Results The apparent clearance of PEG-Intron decreased after repeated dosing. The clearance at treatment week 4 was 42.3 l day,1 (patients with CLcr 120 ml min,1) with interpatient variability 30%. At treatment week 48, the clearance value was reduced to 69% of its week 4 value. CLcr, a composite variable calculated from body weight, sex, age and serum creatinine, had a small but statistically significant influence on the clearance of PEG-Intron. The clearance of PEG-Intron in patients with CML was 40% higher than that of hepatitis C virus-infected patients. Conclusion The dose of PEG-Intron 6.0 µg kg,1 week,1 appeared appropriate in the treatment of patients with CML. [source] Pharmacokinetics of ribavirin in patients with hepatitis C virusBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2006Janet R. Wade Aim A population pharmacokinetic analysis was performed using plasma concentration data (n = 7025) from 380 patients to examine the relationship between ribavirin dose and its pharmacokinetics. Methods Ribavirin pharmacokinetics were described by a three-compartment model with sequential zero-order and a first-order absorption processes. Interoccasion variability and food effects were included. Results Lean body weight (range 41,91 kg) was the only covariate with a clinically significant influence on ribavirin pharmacokinetics, affecting clearance (15.3,23.9 l h,1) and the volume of the larger peripheral compartment. Conclusion The model provided a good description of the available data, confirmed by accurate estimates of parameter values and low residual variability (17%). [source] | |||||||||||||||||||