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  • bioavailability  (65)
  • 04. Solid Earth::04.06. Seismology::04.06.03. Earthquake source and dynamics
  • 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
  • Geodesy
  • Modelling
  • Springer  (98)
  • 2005-2009  (23)
  • 1975-1979  (75)
  • 1950-1954
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Years
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  • 1
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    Springer
    In:  Amsterdam, Springer, vol. 1, pp. 225, (1-4020-3353-2)
    Publication Date: 2005
    Keywords: Tsunami(s) ; Earthquake risk ; Earthquake precursor: prediction research ; Review article ; Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Modelling ; NATHAZ ; measurement, ; tsunami ; model, ; data ; assimilation, ; data ; inversion, ; tsunami ; warning, ; tsunameters, ; forecast, ; hazard ; mitigation
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  • 2
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    In:  Corporate, Florida, Springer, vol. Developments in Petroleum Science vol. 15B, no. Publ. No. 12, pp. 9, (3-540-24165-5, XXVI + 228 p.)
    Publication Date: 2006
    Description: This book provides a summary of geodynamic results from Iceland that presently are found in a great number of scientific articles, but have not been collected before in a book
    Keywords: Textbook of geodesy ; Crustal deformation (cf. Earthquake precursor: deformation or strain) ; Geodesy ; Plate tectonics ; GeodesyY
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  • 3
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    In:  Berlin, Springer, vol. 3, no. ALEX(01)-FR-77-01, AFTAC Contract F08606-76-C-0025, pp. 329, (ISBN: 3-540-27983-0, XII + 238 p., 77 illus., 13 in colour with CD-ROM)
    Publication Date: 2006
    Description: Contents: Data Analysis in Earth Sciences - Introduction to MATLAB - Univariate Statistics - Bivariate Statistics - Time-Series Analysis - Signal Processing - Spatial Data including Digital Elevation Models - Image Processing including Processing and Georeferencing of Satellite Images - Multivariate Statistics; IfGW Uni Potsdam
    Keywords: Data analysis / ~ processing ; Modelling ; software ; Textbook of geophysics ; Statistical investigations ; digital signal analysis (also DSP) ; DSP ; Time series analysis ; Digital elevation model ; geographic ; coordinates ; Mapping ; Toolbox
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  • 4
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    In:  Cambridge, Springer, vol. LXXVIII, no. 2, pp. 125-169, (ISBN: 3-540-42642-6, Approx. 620 p. 30 illus., Hardcover)
    Publication Date: 2006
    Keywords: Crustal deformation (cf. Earthquake precursor: deformation or strain) ; Volcanology ; Geodesy ; Global Positioning System ; InSAR ; Textbook of geodesy
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  • 5
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    In:  Amsterdam, 490 pp., Springer, vol. 11, no. Publ. No. 12, pp. 127, (1-4020-4233-7 (hc), 1-4020-4234-5 (sc), X + 413 p.)
    Publication Date: 2006
    Description: Tectonic motion of the Adria microplate exerts a first-order control on the tectonics, geology, seismology, resource distribution, and the geological hazards across a broad zone of south-central Europe and the north-central Mediterranean... This workshop brought together a distinguished international group of scientists working in the peri-Adriatic region to: (1) review research activities and results, (2) share technical expertise, and (3) provide a springboard for future collaborative research on Adria geodynamics. Areas of agreement were identified, as well as remaining areas of debate. In addition, attention focused on important scientific questions and the potential for international and interdisciplinary research in the future
    Keywords: Plate tectonics ; Geodesy ; Tectonics ; Earthquake hazard ; Italy ; Croatia
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  • 6
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    In:  Professional Paper, Perspectives in Modern Seismology, Berlin, Springer, vol. 105, 223 pp., no. 231, pp. 13-30, (ISBN: 3-540-23712-7)
    Publication Date: 2005
    Keywords: Earthquake risk ; Site amplification ; Strong motions ; Earthquake engineering, engineering seismology ; Synthetic seismograms ; NOISE ; Nakamura ; Modelling ; Cologne ; DFNK ; Faecke ; Facke
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  • 7
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    In:  Geo-Information for Disaster Management, Berlin, Heidelberg, New York, Springer, vol. 12, pp. 323-336, (ISBN 3-540-24988-5)
    Publication Date: 2005
    Keywords: Textbook of informatics ; Earthquake hazard ; Earthquake risk ; Tsunami(s) ; Proceedings of a conference ; Earthquake ; Indonesia ; Geodesy
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  • 8
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    Springer
    In:  Bull., Polar Proj. OP-O3A4, Perspectives in Modern Seismology, London, Springer, vol. 201, no. XVI:, pp. 169-184, (ISBN: 3-540-23712-7)
    Publication Date: 2005
    Keywords: Crustal deformation (cf. Earthquake precursor: deformation or strain) ; Geodesy ; Finite Element Method ; Modelling ; Three dimensional ; Seismology ; Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Bucharest ; Romania ; Earthquake risk
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  • 9
    Publication Date: 2021-06-21
    Description: Earthquake early warning systems (EEWS), based on real-time prediction of ground motion or structural response measures, may play a role in re- ducing vulnerability and/or exposure of buildings and lifelines. Indeed, seismologists have recently developed efficient methods for real-time es- timation of an event’s magnitude and location based on limited informa- tion of the P-waves. Therefore, when an event occurs, estimates of magni- tude and source-to-site distance are available, and the prediction of the structural demand at the site may be performed by Probabilistic Seismic Hazard Analysis (PSHA) and then by Probabilistic Seismic Demand Analysis (PSDA) depending upon EEWS measures. Such an approach contains a higher level of information with respect to traditional seismic risk analysis and may be used for real-time risk management. However, this kind of prediction is performed in very uncertain conditions which may affect the effectiveness of the system and therefore have to be taken into due account. In the present study the performance of the EWWS under development in the Campania region (southern Italy) is assessed by simu- lation. The earthquake localization is formulated in a Voronoi cells ap- proach, while a Bayesian method is used for magnitude estimation. Simu- lation has an empirical basis but requires no recorded signals. Our results, in terms of hazard analysis and false/missed alarm probabilities, lead us to conclude that the PSHA depending upon the EEWS significantly improves seismic risk prediction at the site and is close to what could be produced if magnitude and distance were deterministically known.
    Description: Published
    Description: 211-232
    Description: 4.1. Metodologie sismologiche per l'ingegneria sismica
    Description: reserved
    Keywords: Earthquake Early ; Campania Region ; 04. Solid Earth::04.06. Seismology::04.06.03. Earthquake source and dynamics ; 04. Solid Earth::04.06. Seismology::04.06.04. Ground motion ; 04. Solid Earth::04.06. Seismology::04.06.11. Seismic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: book chapter
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  • 10
    Publication Date: 2017-04-03
    Description: We compare the results obtained from the modelling of EDM, GPS, levelling and tilt data measured in the first part of the 19911993 eruption at Etna to the InSAR data acquired during the second part. The geodetic changes are very marked in the first half of the eruption and constrain a deflation source located at a few kilometers of depth ( 3 km b.s.l.), in agreement with other independent geophysical evidence. SAR data, available during the second part of the eruption, were analysed for different time intervals in the second part of the eruption. The interpretation of SAR interferograms reveals a large-scale but less marked deflation of the volcano that could be caused by a deeper source. This second source is in accord with a second deeper anomaly revealed by recent seismic investigations. The combination of geodetic data modelling and SAR images suggests a complex plumbing system composed at least of two possible storage regions located at different depths.
    Description: Published
    Description: 1345-1357
    Description: partially_open
    Keywords: Geodesy ; SAR Interferometry ; ground deformation ; Mt. Etna volcano ; 04. Solid Earth::04.03. Geodesy::04.03.06. Measurements and monitoring ; 04. Solid Earth::04.03. Geodesy::04.03.07. Satellite geodesy ; 04. Solid Earth::04.03. Geodesy::04.03.09. Instruments and techniques
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 11
    Publication Date: 2017-04-04
    Description: Analysis of the historical records of Etnas eruptive activity for the past three centuries shows that, after the large 1669 eruption, a period of about 60 years of low-level activity followed. Starting from 1727, explosive activity (strombolian, lava fountaining and subplinian) at the summit crater increased exponentially to the present day. Since 1763, the frequency of flank eruptions also increased and this value remained high until 1960; afterward it further increased sharply. In fact, the number of summit and flank eruptions between 1961 and 2003 was four times greater than that of the pre-1960 period. This long-term trend of escalating activity rules out a pattern of cyclic behaviour of the volcano. We propose instead that the 16702003 period most likely characterises a single eruptive cycle which began after the large 1669 eruption and which is still continuing. On the basis of the eruptive style, two distinct types of flank eruptions are recognised: Class A and Class B. Class A eruptions are mostly effusive with associated weak strombolian activity; Class B eruptions are characterised by effusive activity accompanied by intense, long-lasting, strombolian and lava fountaining activity that produces copious tephra fallouts, as during the 2001 and 20022003 eruptions. Over the past three centuries, seven Class B eruptions have taken place with vents located mainly on the south-eastern flank, indicating that this sector of the volcano is a preferential zone for the intrusion of volatile-rich magma rising from the deeper region of the Etna plumbing system.
    Description: Published
    Description: 732-742
    Description: partially_open
    Keywords: Etna ; Historical record ; Summit activity ; Flank eruptions ; Eruptive behaviour ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 12
    Publication Date: 2017-04-04
    Description: The Monte Nuovo eruption is the most recent event that occurred at Phlegrean Fields (Italy) and lasted from 29 September to 6 October 1538. It was characterized by 2 days of quasi-sustained phreatomagmatic activity generating pumice-bearing pyroclastic density currents and forming a 130-m-high tuff cone (Lower Member deposits). The activity resumed after a pause of 2 days with two discrete Vulcanian explosions that emplaced radially distributed, scoria-bearing pyroclastic flows (Upper Member deposits). The juvenile products of Lower and Upper Members are, respectively, phenocryst-poor, light-coloured pumice and dark scoria fragments with K-phonolitic bulk compositions, identical in terms of both major and trace elements. Groundmass is formed by variable proportions of K-feldspar and glass, along with minor sodalite and Fe-Ti oxide present in the most crystallized samples. Investigations of groundmass compositions and textures were performed to assess the mechanisms of magma ascent, degassing and fragmentation along the conduit and implications for the eruptive dynamics. In pumice of the Lower Member groundmass crystal content increases from 13 to 28 vol% from the base to the top of the sequence. Products of the Upper Member consist of clasts with a groundmass crystal content between 30 and 40 vol% and of totally crystallized fragments. Crystal size distributions of groundmass feldspars shift from a single population at the base of the Lower Member to a double population in the remaining part of the sequence. The average size of both populations regularly increases from the Lower to the Upper Member. Crystal number density increases by two orders of magnitude from the Lower to the Upper Member, suggesting that nucleation dominated during the second phase of the eruption. The overall morphological, compositional and textural data suggest that the juvenile components of the Monte Nuovo eruption are likely to record variations of the magma properties within the conduit. The different textures of pumice clasts from the Lower Member possibly reflect horizontal gradients of the physical properties (P, T) of the ascending magma column, while scoriae from the second phase are thought to result from the disruption of a slowly rising plug crystallizing in response to degassing. In particular, crystal size distribution data point to syn-eruptive degassing-induced crystallization as responsible for the transition in eruptive style from the first to the second phase of the eruption. This mechanism not only has been proved to profoundly affect the dynamics of dome-forming calc-alkaline eruptions, but may also have a strong influence in driving the eruption dynamics of alkaline magmas of intermediate to evolved compositions.
    Description: Published
    Description: 601-621
    Description: reserved
    Keywords: Phlegrean Fields ; Vulcanian explosion ; Degassing ; Groundmass crystallization ; Eruption dynamics ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.02. Experimental volcanism ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
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  • 13
    Publication Date: 2017-04-04
    Description: For early-warning applications in particular, the reliability and efficiency of rapid scenario generation strongly depend on the availability of reliable strong ground-motion prediction tools. If shake maps are used to represent patterns of potential damage as a consequence of large earthquakes, attenuation relations are used as a tool for predicting peak ground-motion parameters and intensities. One of the limitations in the use of attenuation relations is that these have only rarely been retrieved from data collected in the same tectonic environment in which the prediction has to be performed. As a consequence, strong ground motion can result in underestimations or overestimations with respect to the recorded data. This also holds for Italy, and in particular for the Southern Apennines, due to limitations in the available databases, both in terms of distances and magnitude. Moreover, for “real-time” early-warning applications, it is important to have attenuation models for which the parameters can be easily upgraded when new data are collected, whether this has to be done during the earthquake rupture occurrence or in the post-event, when all the strong motion waveforms are available. Here we present a strong-motion attenuation relation for early-warning applications in the Campania region (Southern Apennines), Italy. The model has a classical analytical formulation, and its coefficients were retrieved from a synthetic strong-motion database created by using a stochastic approach. The input parameters for the simulation technique were obtained through the spectral analysis of waveforms of earthquakes recorded by the Istituto Nazionale di Geofisica e Vulcanologia (INGV) network for a magnitude range Md (1.5,5.0) in the last fifteen years, and they have been extrapolated to cover a larger range. To validate the inferred relation, comparisons with two existing attenuation relations are presented. The results show that the calibration of the attenuation parameters, i.e., geometric spreading, quality factor Q, static stress drop values along with their uncertainties, are the main concern.
    Description: Published
    Description: 133-152
    Description: 4.1. Metodologie sismologiche per l'ingegneria sismica
    Description: reserved
    Keywords: A Strong Motion ; Earlywarning ; 04. Solid Earth::04.06. Seismology::04.06.03. Earthquake source and dynamics ; 04. Solid Earth::04.06. Seismology::04.06.04. Ground motion ; 04. Solid Earth::04.06. Seismology::04.06.11. Seismic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: book chapter
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  • 14
    Publication Date: 2017-04-04
    Description: In the framework of an ongoing project financed by the Campania Region, a prototype system for seismic early and post-event warning is being developed and tested, based on a dense, wide dynamic seismic network (ISNet) and under installation in the Apennine belt region. This paper reports the characteristics of the seismic network, focussing on the required technological innovation of the different seismic network components (data-logger, sensors and data communication). To ensure a highly dynamic recording range, each station is equipped with two types of sensors: a strong-motion accelerometer and a velocimeter. Data acquisition at the seismic stations is performed using Osiris-6 model data-loggers made by Agecodagis. Each station is supplied with two (120 W) solar panels and two 130 Ah gel cell batteries, ensuring 72-h autonomy for the seismic and radio communication equipment. The site is also equipped with a GSM/GPRS programmable control/alarm system connected to several environmental sensors (door forcing, solar panel controller, battery, fire, etc) and through which the site status is known in real time. The data are stored locally on the hard-disk and, at the same time, continuously transmitted by the SeedLink protocol to local acquisition/analysis nodes (Local Control Center) via Wireless LAN bridge. At each LCC site runs a linux Earthworm system which stores and manages the acquired data stream. The real-time analysis system will perform event detection and localization based on triggers coming from data-loggers and parametric information coming from the other LCCs. Once an event is detected, the system will performs automatic magnitude and focal mechanism estimations. In the immediate post-event period, the RISSC performs shaking map calculations using parameters from the LCCs and/or data from the event database. The recorded earthquake data are stored into an event database, to be available for distribution and visualization for further off-line analyses. The seismic network will be completed in two stages: • Deployment of 30 seismic stations along the southern Apennine chain (to date almost completed) • Setting up a carrier-class radio communication system for fast and reliable data transmission, and installation of 10 additional seismic stations.
    Description: Published
    Description: 325 - 341
    Description: 4.1. Metodologie sismologiche per l'ingegneria sismica
    Description: reserved
    Keywords: Monitoring Infrastructure ; Early-warning Applications ; 04. Solid Earth::04.06. Seismology::04.06.03. Earthquake source and dynamics ; 04. Solid Earth::04.06. Seismology::04.06.04. Ground motion ; 04. Solid Earth::04.06. Seismology::04.06.11. Seismic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: book chapter
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  • 15
    Publication Date: 2017-04-04
    Description: Ground deformation occurring on the southern flank of Mt Etna volcano during the JulyAugust 2001 eruption was monitored by GPS measurements along an EW profile crossing the fissure system. This profile was measured eight times during the eruption, using the 'stop and go' semi-kinematic technique. Horizontal and vertical displacements between GPS surveys are reported for each station. The most significant event is a deformation episode occurring during the first week of the eruption, between 2527 July. Displacements were measured on benchmarks close to the eruptive fissure and the tensile 1989 fracture. Data inversions for measured displacements were performed using the Okada model. The model shows the narrowing of the 2001 dyke accompanied by a dextral dislocation along an east-dipping fault, parallel to the 1989 fracture.
    Description: Published
    Description: 336-341
    Description: partially_open
    Keywords: GPS ; Ground deformation ; Modelling ; Volcano monitoring ; 04. Solid Earth::04.03. Geodesy::04.03.07. Satellite geodesy ; 04. Solid Earth::04.03. Geodesy::04.03.09. Instruments and techniques ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 16
    Publication Date: 2017-04-04
    Description: The 200203 Mt Etna flank eruption began on 26 October 2002 and finished on 28 January 2003, after three months of continuous explosive activity and discontinuous lava flow output. The eruption involved the opening of eruptive fissures on the NE and S flanks of the volcano, with lava flow output and fire fountaining until 5 November. After this date, the eruption continued exclusively on the S flank, with continuous explosive activity and lava flows active between 13 November and 28 January 2003. Multi-disciplinary data collected during the eruption (petrology, analyses of ash components, gas geochemistry, field surveys, thermal mapping and structural surveys) allowed us to analyse the dynamics of the eruption. The eruption was triggered either by (i) accumulation and eventual ascent of magma from depth or (ii) depressurisation of the edifice due to spreading of the eastern flank of the volcano. The extraordinary explosivity makes the 200203 eruption a unique event in the last 300 years, comparable only with La Montagnola 1763 and the 2001 Lower Vents eruptions. A notable feature of the eruption was also the simultaneous effusion of lavas with different composition and emplacement features. Magma erupted from the NE fissure represented the partially degassed magma fraction normally residing within the central conduits and the shallow plumbing system. The magma that erupted from the S fissure was the relatively undegassed, volatile-rich, buoyant fraction which drained the deep feeding system, bypassing the central conduits. This is typical of most Etnean eccentric eruptions. We believe that there is a high probability that Mount Etna has entered a new eruptive phase, with magma being supplied to a deep reservoir independent from the central conduit, that could periodically produce sufficient overpressure to propagate a dyke to the surface and generate further flank eruptions.
    Description: Published
    Description: 314-330
    Description: partially_open
    Keywords: Multi-disciplinary study ; Mount Etna ; 2002–03 eruption ; Eccentric eruptions ; Flank activity ; Etna feeding system ; Volcanic processes ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 17
    Publication Date: 2017-04-04
    Description: It has been argued that the dominant period T_p derived from the initial seconds of a seismogram, hence only depending on the initial phases of earthquake rupture, seems to scale with the final size of the earthquake. We provide a physical interpretation for the observed scaling and explain how the final earthquake size could be controlled by the initial phase of rupture.
    Description: Published
    Description: 9-19
    Description: 3.1. Fisica dei terremoti
    Description: reserved
    Keywords: early warning ; fracture energy ; 04. Solid Earth::04.06. Seismology::04.06.03. Earthquake source and dynamics
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: book chapter
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  • 18
    Publication Date: 2017-04-04
    Description: Mount Etna is an open conduit volcano, characterised by persistent activity, consisting of degassing and explosive phenomena at summit craters, frequent flank eruptions, and more rarely, eccentric eruptions. All eruption typologies can give rise to lava flows, which represent the greatest hazard by the volcano to the inhabited areas. Historical documents and scientific papers related to the 20th century effusive activity have been examined in detail, and volcanological parameters have been compiled in a database. The cumulative curve of emitted lava volume highlights the presence of two main eruptive periods: (a) the 1900–1971 interval, characterised by a moderate slope of the curve, amounting to 436 · 106 m3 of lava with average effusion rate of 0.2 m3/s and (b) the 1971–1999 period, in which a significant increase in eruption frequency is associated with a large issued lava volume (767 · 106 m3) and a higher effusion rate (0.8 m3/s). The collected data have been plotted to highlight different eruptive behaviour as a function of eruptive periods and summit vs. flank eruptions. The latter have been further subdivided into two categories: eruptions characterised by high effusion rates and short duration, and eruptions dominated by low effusion rate, long duration and larger volume of erupted lava. Circular zones around the summit area have been drawn for summit eruptions based on the maximum lava flow length; flank eruptions have been considered by taking into account the eruptive fracture elevation and combining them with lava flow lengths of 4 and 6 km. This work highlights that the greatest lava flow hazard at Etna is on the south and east sectors of the volcano. This should be properly considered in future land-use planning by local authorities.
    Description: Published
    Description: 407–443
    Description: 4.3. TTC - Scenari di pericolosità vulcanica
    Description: JCR Journal
    Description: reserved
    Keywords: Mt. Etna ; effusive activity ; database ; lava flow length ; eruptive fractures ; vent elevation ; hazard zonation ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 19
    Publication Date: 2017-04-04
    Description: Flank instability and collapse are observed at many volcanoes. Among these, Mt. Etna is characterized by the spreading of its eastern and southern flanks. The eastern spreading area is bordered to the north by the EW-trending Pernicana Fault System (PFS). During the 20022003 Etna eruption, ground fracturing along the PFS migrated eastward from the NE Rift, to as far as the 18 km distant coastline. The deformation consisted of dextral en-echelon segments, with sinistral and normal kinematics. Both of these components of displacement were one order of magnitude larger (~1 m) in the western, previously known, portion of the PFS with respect to the newly surveyed (~9 km long) eastern section (~0.1 m). This eastern section is located along a pre-existing, but previously unknown, fault, where displaced man-made structures give overall slip rates (11.9 cm/year), only slightly lower than those calculated for the western portion (1.42.3 cm/year). After an initial rapid motion during the first days of the 20022003 eruption, movement of the western portion of the PFS decreased dramatically, while parts of the eastern portion continued to move. These data suggest a model of spreading of the eastern flank of Etna along the PFS, characterized by eruptions along the NE Rift, instantaneous, short-lived, meter-scale displacements along the western PFS and more long-lived centimeter-scale displacements along the eastern PFS. The surface deformation then migrated southwards, reactivating, one after the other, the NNWSSE-trending Timpe and Trecastagni faults, with displacements of ~0.1 and ~0.04 m, respectively. These structures, along with the PFS, mark the boundaries of two adjacent blocks, moving at different times and rates. The new extent of the PFS and previous activity over its full length indicate that the sliding eastern flank extends well below the Ionian Sea. The clustering of seismic activity above 4 km b.s.l. during the eruption suggests a deep décollement for the moving mass. The collected data thus suggests a significant movement (volume 〉1,100 km3) of the eastern flank of Etna, both on-shore and off-shore.
    Description: Published
    Description: 417-430
    Description: partially_open
    Keywords: Volcano spreading ; Fracturing ; Mt. Etna ; Pernicana Fault System ; NE Rift ; 04. Solid Earth::04.04. Geology::04.04.09. Structural geology ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
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  • 20
    Publication Date: 2017-04-04
    Description: We have characterized pumice products belonging to the climactic phase of the 800-year-b.p. Quilotoa eruption. Bulk rock compositions, petrography, mineral, and glass chemistry and textural investigations were performed on the three end-member pumice types, namely white, gray, and mingled pumices. All the investigated pumice clasts are dacites characterized by the same bulk rock composition and mineralogical assemblage, but glass compositions and bulk textures change according to different pumice types. White pumice has higher crystallinity (~48 wt%), abundant euhedral pheno/microphenocrysts, no groundmass microlites, the most evolved glass compositions (7478 wt% SiO2), and heterogeneous vesicle populations marked by deformed and highly coalesced vesicles with thin walls. Gray pumice exhibits lower crystallinity (2936 wt%), abundant broken and/or resorbed crystals, ubiquitous groundmass phenocryst fragments and microlites, the widest range of glass compositions (6978 wt% SiO2), and quite homogeneous poorly deformed and coalesced vesicles with thicker walls. Mingled pumices are characterized by the alternation of bands or patches with white and gray pumice compositional and textural characteristics. We attribute heterogeneities in glass compositions and crystal and vesicle textures to processes occurring within volcanic conduits as magma is ascending to the surface. In particular, the above observations and results are consistent with an origin of a gray magma by heating of the original white magma in a strongly sheared region of the conduit because of a mechanism of viscous dissipation and crystal grinding and resorption at the conduit walls. The less viscous gray magma, therefore, would enable the onset and preservation of a high mass flux of the eruption otherwise difficult to explain for highly viscous crystal-rich dacitic magmas.
    Description: Published
    Description: 307-321
    Description: partially_open
    Keywords: Plinian eruption ; Crystal-rich magma ; Crystal grinding ; Pumice types ; Viscous dissipation ; 04. Solid Earth::04.08. Volcanology::04.08.03. Magmas ; 05. General::05.02. Data dissemination::05.02.03. Volcanic eruptions
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  • 21
    Publication Date: 2017-04-04
    Description: A prototype system for earthquake early warning and rapid shake map evaluation is being developed and tested in southern Italy based on a dense, dynamic seismic network (accelerometers + seismometers) under installation in the Apenninic belt region (Irpinia Seismic Network). It can be classified as a regional Earthquake Early Warning System consisting of a broad-based seismic sensor network covering a portion or the entire area which is threatened by the quake's strike. The real time magnitude estimate will take advantage from the high spatial density of the network in the source region and the broad dynamic range of installed instruments. Based on the offline analysis of high quality strong-motion data bases recorded in Italy, several methods are envisaged, using different observed quantities (peak amplitude, dominant frequency, square velocity integral, …) to be measured on seismograms, as a function of time, both on P and early-S wave signals. Results from the analysis of the Italian strong motion database point out the possibility of using low-pass filtered displacement and velocity peak amplitudes measured in time windows lasting less than 3-4 sec after the first P- or S-wave arrivals. These parameters show they are robustly correlated with moment magnitude. The correlation found of 3Hz low-pass filtered PGV and PGD with magnitude is discussed and interpreted in terms of plausible dynamic models of the earthquake rupture process during its initial stage.
    Description: Published
    Description: 45-63
    Description: 4.1. Metodologie sismologiche per l'ingegneria sismica
    Description: reserved
    Keywords: Real-time Estimation ; Magnitude ; Seismic Early Warning ; 04. Solid Earth::04.06. Seismology::04.06.03. Earthquake source and dynamics ; 04. Solid Earth::04.06. Seismology::04.06.04. Ground motion ; 04. Solid Earth::04.06. Seismology::04.06.11. Seismic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 22
    Publication Date: 2017-04-04
    Description: The southernmost sector of the Italian peninsula is crossed by an almost continuous seismogenic belt capable of producing M ~ 7 earthquakes and extending from the Calabrian Arc, through the Messina Straits, as far as Southeastern Sicily. Though large earthquakes occurring in this region during the last Millennium are fairly well known from the historical point of view and seismic catalogues may be considered complete for destructive and badly damaging events (IX £ Io £ XI MCS), the knowledge and seismic completeness of moderate earthquakes can be improved by investigating other kinds of documentary sources not explored by the classical seismological tradition. In this paper, we present a case study explanatory of the problem, regarding the Ionian coast between the Messina Straits and Mount Etna volcano, an area of North-eastern Sicily lacking evidence of relevant seismic activity in historical times. Now, after a systematic analysis of the 18th century journalistic sources (gazettes), this gap can be partly filled by the rediscovery of a seismic sequence that took place in 1780. According to the available catalogues, the only event on record for this year is a minor shock (Io = VI MCS, Mw = 4.8) recorded in Messina on March 28, 1780. The newly discovered data allow to reinstate it as the mainshock (Io = VII–VIII MCS, Mw = 5.6) of a significant seismic period, which went on from March to June 1780, causing severe damage along the Ionian coast of North-eastern Sicily. The source responsible for this event appears located offshore, 40-km south of the previous determination, and is consistent with the Taormina Fault suggested by the geological literature, developing in the low seismic rate zone at the southernmost termination of the 1908 Messina earthquake fault.
    Description: Published
    Description: reserved
    Keywords: Historical seismology ; Macroseismic data ; MCS-EMS intensity scales ; 1780 Seismic sequence ; Seismotectonics ; NE Sicily ; 04. Solid Earth::04.06. Seismology::04.06.03. Earthquake source and dynamics ; 04. Solid Earth::04.06. Seismology::04.06.05. Historical seismology
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    Type: article
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  • 23
    Publication Date: 2022-05-30
    Description: Scientific investigations in Antarctica are, for many different reasons, a challenging and fascinating task. Measurements, observations and field operations must be carefully planned well in advance and the capacity of successfully meeting the goals of a scientific project is often related to the capacity of forecasting and anticipating the many different potential mishaps. In order to do that, experience and logistic support are crucial. On the scientific side, the team must be aware of its tasks and be prepared to carry out observations in a hostile environment: both technology and human resources have to be suitably selected, prepared, tested and trained. On the logistic side, nations, institutions and any other organisation involved in the expeditions must ensure the proper amount of competence and practical support. The history of modern Italian Antarctic expeditions dates back to the middle 80’s when the first infrastructures of “Mario Zucchelli Station”, formerly Terra Nova Bay Station, were settled at Terra Nova Bay, Northern Victoria Land. Only a few years later, the first geodetic infrastructures were planned and built. Italian geodetic facilities and activities were, ever since, being constantly maintained and developed. Nowadays, the most remarkable geodetic infrastructures are the permanent Global Positioning System (GPS) station (TNB1) installed at Mario Zucchelli and the GPS geodetic network Victoria Land Network for DEFormation control (VLNDEF) entirely deployed on an area extending between 71° S and 76° S and 160° E and 170° E. These facilities do not only allow carrying out utmost geodetic investigations but also posses interesting capacities on the international multidisciplinary scientific scenario. In order to fully exploit their potentiality, management and maintenance of the infrastructure are crucial; nevertheless, in order to perform high quality scientific research, these abilities must be coupled with the knowledge concerning a proper use and a correct processing of the information that these infrastructures can provide. This work focuses on the different methods that can be applied to process the observations that are performed with GPS technique in Northern Victoria Land, aiming at reaching the highest accuracy of results and assuring the larger significance and versatility of the processing outcomes. Three software were used for the analysis, namely: Bernese v.5.0, Gipsy/Oasis II and Gamit/Globk. The working data sets are (i) the permanent GPS station TNB1 observations continuously performed since 1998 and (ii) the five episodic campaigns performed on the sites of VLNDEF. The two infrastructures can be regarded as neat examples of standard geodetic installation in Antarctica. Therefore, the technological solutions that were adopted and applied for establishing the GPS permanent station and the VLNDEF geodetic network as well as the data processing strategies and the data analysis procedures that were tested on their observation will be illustrated in detail. The results will be presented, compared and discussed. Furthermore, their potentials and role in geodetic research will be carefully described; their versatility will also be highlighted in the foreground of a multidisciplinary Antarctic international scientific activity.
    Description: Published
    Description: 37-72
    Description: 1.8. Osservazioni di geofisica ambientale
    Description: reserved
    Keywords: Antarctica ; Geodesy ; Geodetic Infrastructures ; GPS ; 01. Atmosphere::01.01. Atmosphere::01.01.08. Instruments and techniques
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 24
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    European journal of clinical pharmacology 8 (1975), S. 293-299 
    ISSN: 1432-1041
    Keywords: Rifampicin ; p-aminosalicylic acid ; bentonite ; drug interaction ; bioavailability ; drug adsorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability (plasma concentrations, AUC and urinary excretion) of an oral solution of rifampicin was investigated in six healthy volunteers. Simultaneous administration of PAS granules produced a significant decrease in the absorption of RMP, whereas Na-PAS tablets had no effect. This indicated that the dosage form of the granules and not PAS itself was responsible for the interaction, and that the dissolution of RMP was not involved. The interaction could be reproduced by giving dummy granules that contained the same excipients but no PAS. The disintegration and dissolution of PAS granulesin vitro correlated well with the disappearance of RMP from the solution. The major excipient of the granules, bentonite (a mineral closely related to kaolin), was found to adsorb rifampicin rapidly and strongly.
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  • 25
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    European journal of clinical pharmacology 8 (1975), S. 365-370 
    ISSN: 1432-1041
    Keywords: Particle size ; bioavailability ; digoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of digoxin in three tablets prepared from materials with different particle sizes was measured in healthy volunteers in a cross-over study using an alcoholic solution of digoxin as a reference standard. Its bioavailability in tablets with particle sizes of 7 µ or 13 µ was 78–97% of that of digoxin in solution. The tablet with largest particle size (102 µ) showed markedly lower bioavailability than the reference solution, namely 39%. It is obvious that particle size is an important determinant of the dissolution rate and bioavailability of digoxin.
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  • 26
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    European journal of clinical pharmacology 9 (1975), S. 209-212 
    ISSN: 1432-1041
    Keywords: Anticonvulsants ; phenytoin ; diphenylhydantoin ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma phenytoin levels were measured in 60 patients under steady-state conditions for a period of six weeks. During the trial, the preparation of phenytoin was changed from Phenytoin BP (Regent) to Epanutin Infatabs. A significant increase in plasma phenytoin levels following the change of tablet was matched by a decrease in the number of seizures.
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  • 27
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    European journal of clinical pharmacology 9 (1975), S. 213-218 
    ISSN: 1432-1041
    Keywords: Phenytoin ; diphenylhydantoin ; anticonvulsants ; bioavailability ; drug absorption ; generic inequivalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to evaluate the bioavailability of four different brands of phenytoin (diphenylhydantoin, DPH) tablets single doses of 600 mg DPH in acid form were given to six volunteers in a cross-over study. A micronized DPH-acid suspension was used as the reference standard. Significant differences between various products were found. The areas under the serum DPH concentration-time curves (AUC) were 26, 59, 68 and 90 per cent of the AUC of the DPH suspension. The peak serum DPH concentrations using the different tablets were 24, 54, 55 and 80 per cent of the peak value of the DPH suspension. It is likely that the differences in bio-availability of the DPH tablets are of clinical significance.
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  • 28
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    European journal of clinical pharmacology 9 (1976), S. 315-317 
    ISSN: 1432-1041
    Keywords: Tolamolol ; bioavailability ; maximum exercise tachycardia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bioavailability of capsule and tablet formulations of tolamolol were compared by measuring plasma concentration of tolamolol and reduction in maximum exercise heart rate over a period of twelve hours in eight healthy subjects in a two-way cross-over study. Tolamol was absorbed more rapidly from capsules than from tablets; this did not result in any significant difference in the reduction in maximum exercise heart rate between the two formulations. There was no significant difference between area under curve of reduction in exercise tachycardia and area under curve of plasma concentration of tolamolol for the two formulations. Reduction in maximum exercise heart rate was related to logarithm of plasma concentration of tolamolol between two and twelve hours after both formulations.
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  • 29
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    European journal of clinical pharmacology 9 (1976), S. 373-379 
    ISSN: 1432-1041
    Keywords: Methyldigoxin ; repetitive doses ; bioavailability ; deep compartments ; oral and i.v. dose ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To obtain true half lives, glycoside elimination from six healthy subjects was studied for 14 days after multiple intravenous doses or oral administration of a daily maintenance dose of β-methyldigoxin 0.3 mg. After oral or intravenous administration of β-methyldigoxin ceased, the plasma concentrations declined from the 14th to the 16th days with a half life of 1.7 days. From the 16th to the 20th day a change from a shorter to a longer half life of 2.8 and 2.9 days was observed. Similar half lives were found in urine: after the last dose the initial slope from the 14th to the 16th day had a half life of 1.8 days, and the terminal slope had one of 3.2 days. The results indicate release of the glycoside from slowly equilibrating tissues.
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  • 30
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    European journal of clinical pharmacology 8 (1975), S. 371-376 
    ISSN: 1432-1041
    Keywords: Digoxin ; bioavailability ; plasma levels ; cumulative urinary excretion ; particle size ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Various brands of digoxin tablets, and even different batches of one brand, may differ greatly in bioavailability. Digoxin-Sandoz® tablets have been compared with Lanoxin® manufactured between 1969 and 1972 and after May 1972. Comparisons were also made between and within batches of Digoxin-Sandoz tablets. Three separate cross-over studies were conducted involving a total of 20 volunteers. Digoxin-Sandoz tablets were shown to have a constant bioavailability and to produce plasma concentrations very similar to “new” Lanoxin. Storage for 2 years of one batch of Digoxin-Sandoz did not alter the bioavailability. Particle size was shown to influence bioavailability. Care should be exercised when plasma data alone are interpreted as an index of bioavailability. Measures of bioavailability based on plasma data obtained up to 6 h after administration differed from those based on cumulative urinary excretion data (in this study by a factor of about 2), which can lead to the belief that a difference in bioavailability is much greater than is actually the case. Data from cumulative urinary excretion, collected over a sufficiently long period of time, are likely to be the most reliable method for determining the bioavailability of a substance such as digoxin.
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  • 31
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    European journal of clinical pharmacology 16 (1979), S. 211-215 
    ISSN: 1432-1041
    Keywords: fluoride ; bioavailability ; calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of milk products on the gastrointestinal absorption of fluoride from sodium fluoride tablets was studied in five healthy subjects. Two different diets were tested: (1) 250 ml standardized milk (3% fat) and (2) 500 ml of milk, 3 pieces of white bread with cheese and 150 ml of yoghurt. The 100% bioavailability of sodium fluoride tablets during fasting was greatly decreased by coadministration of milk products: with Diet 1 the absolute bioavailability calculated from combined plasma and urine data was in the range 50–79% and with Diet 2 it ranged from 50–71%. It is suggested that the decreased bioavailability produced by dairy products should be taken into account when establishing fluoride dosage regimens for prophylaxis of caries.
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  • 32
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    European journal of clinical pharmacology 10 (1976), S. 231-236 
    ISSN: 1432-1041
    Keywords: Digoxin ; beta-methyl-digoxin ; capsules ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The intestinal absorption and urinary elimination rate of total cardioactive material was compared following digoxin and beta-methyldigoxin (BMD) administration to twelve healthy volunteers. Significantly more injected digoxin was recovered in urine. Urinary clearance was more rapid for digoxin, mean half-lives of elimination being 35 hours for digoxin and 40 hours for BMD. Calculated percentage intestinal absorption was lowest for digoxin tablets with a dissolution rate of 77% in one hour, intermediate for BMD tablets, and maximal for an experimental soft gelatin formulation of digoxin in solution. Respective mean values were 75%, 87% and 97%. Similar steady state plasma concentrations followed twice daily ingestion of the 0.25 mg digoxin tablets and 0.20 mg BMD tablets. Mean peak plasma concentration and percentage urinary recovery of ingested dose were higher during continued BMD administration. Between-subject variation in absorption was higher for the digoxin tablets. The comparative intestinal absorption of BMD and digoxin depends upon the formulation. Digoxin is virtually completely absorbed from a solution encapsulated in soft gelatin. Relatively more BMD is eliminated by nonrenal routes.
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  • 33
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    European journal of clinical pharmacology 10 (1976), S. 251-256 
    ISSN: 1432-1041
    Keywords: Sisomicin ; pharmacokinetics ; bioavailability ; two-compartment analysis ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sisomicin, a new single component aminoglycoside antibiotic related to gentamicin c1a, were determined in four healthy volunteers after intravenous and intramuscular administration of a 1 mg/kg dose. The elimination profile of this antibiotic follows two-compartment model kinetics after I.V. administration. The fast (α) and slow (β) disposition rate constants averaged 0.072 and 0.004 min−1, respectively. The volume of distribution at the steady-state averaged 0.185 liters/kg which approximately corresponds to the volume of extracellular space. The physiological availability of an intramuscular dose appeared to be complete. A method of administration adapted to the kinetic properties of the drug is proposed.
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  • 34
    ISSN: 1432-1041
    Keywords: Cefoxitin ; lidocaine ; intramuscular ; bioavailability ; pain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The use of lidocaine HCl solution at concentrations of 0.5 and 1.0% to reconstitute sodium cefoxitin relieves the pain associated with intramuscular injections of the antibiotic. Cefoxitin absorption by the intramuscular route is initially rapid and is virtually complete. Peak serum concentrations, corresponding to about one-half those of a comparable intravenous infusion, are achieved in 30 min. Continuing absorption tends to maintain higher serum concentrations for longer times. Renal clearance and serum half-life of cefoxitin do not appear to be affected by lidocaine at its effective anaesthetic concentrations.
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  • 35
    ISSN: 1432-1041
    Keywords: p-Chlorophenoxyisobutyric acid ; clofibrate ; steady-state plasma concentrations ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations and bioavailability of clofibrinic acid have been estimated under conditions approaching the steady-state during a ten-day period of administration as clofibrate or as a calcium clofibrinate-carbonate combination (1:1 w/w) at a dosage interval of 12 h. Formulation — related differences in bioavailability were not significant, and the 95% confidence limits of these differences were within −2% to +8% of the mean for the reference formulation of clofibrate. The mean steadystate plasma concentrations of clofibrinic acid measured on the tenth day of dosing were 116 µg/ml±22 S.D. and 119 µg/ml±23 S.D. after administration of 885 mg as clofibrate and the calcium clofibrinate-carbonate combination respectively. The peaks of mean plasma concentrations were 70 µg/ml±15 S.D., 119 µg/ml±32 S.D. and 131 µg/ml±26 S.D. on the first, fifth and tenth day of dosing with clofibrate, and 62 µg/ml±13 S.D., 127 µg/ml±S.D. and 143 µg/ml±25 S.D. on the corresponding days of dosing with the calcium clofibrinate-carbonate combination. After the last dose on the tenth day of dosing, the mean apparent half-lives of elimination of clofibrinic acid from plasma were 24.2 h±4.4 S.D. and 25.5 h±3.2 S.D. after administration of clofibrate and the calcium clofibrinate-carbonate combination respectively.
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  • 36
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    European journal of clinical pharmacology 13 (1978), S. 125-128 
    ISSN: 1432-1041
    Keywords: bioavailability ; diuretics ; gastrointestinal absorption ; hydrochlorothiazide ; thiazides ; food effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Hydrochlorothiazide (hct) 75 mg was administered orally to eight healthy volunteers without (Study I) or together with a standardized meal (Study II), and plasma and urine concentrations of hct were analyzed by GLC. The plasma levels of hct were higher initially when the tablets were taken on an empty stomach, but after 5 h they were higher in Study II. There was no difference between the two studies in the area under plasma concentration time curves. The urinary recovery of hct totalled 55.6±4.9 mg when the drug was given with food and 47.4±6.0 when it was taken on an empty stomach. The difference is significant (p〈0.01). As the urinary recovery represents the uptake of hct, it appears that the gastrointestinal absorption of hct is enhanced when the drug is given with food.
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  • 37
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    European journal of clinical pharmacology 10 (1976), S. 257-262 
    ISSN: 1432-1041
    Keywords: Anti-inflammatory and analgesic drug ; indoprofen ; pharmacokinetics ; bioavailability ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a pharmacokinetic study of the new analgesic and anti-inflammatory drug indoprofen, plasma levels and urinary excretion were determined in four healthy volunteers after 100 mg and 200 mg iv, and after 100 mg (capsules) and 200 mg (tablets) oral doses. After iv administration, the mean biological half-life (t1/2 β) was about 2 h (range 1.4 to 3.2 h). The apparent volume of distribution Vdβ ranged between 11 to 17 % of body weight, indicating its limited extravascular distribution. Most of the drug was excreted in urine as glucuronide and a smaller proportion as unchanged indoprofen: the 24 h urinary excretion of these compounds accounted for 67 to 95 % of an iv dose. Peak plasma levels occurred between 30 and 120 minutes after oral administration of 100 mg as capsules or 200 mg as tablets. The mean biological half-life was about 2 h, as after iv administration. The bioavailability of oral doses was assessed using both plasma levels and urinary excretion data. The absorption of capsules and tablets was practically complete, that of the former being faster.
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  • 38
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    European journal of clinical pharmacology 10 (1976), S. 101-108 
    ISSN: 1432-1041
    Keywords: Cardiac glycosides ; methyl proscillaridin ; plasma concentrations ; electrocardiogram ; bioavailability ; 86Rb-erythrocyte assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of this study was to obtain data about the pharmacological properties of a new glycoside derivative in man. Plasma concentrations and ECG parameters were measured after oral and intravenous administration of a single dose of 1.2 mg methyl proscillaridin in 16 healthy volunteers, using a strictly randomized, two-period change-over design. Glycoside concentrations were measured using a modified86Rb-erythrocyte-assay. QT-duration, corrected for frequency (QTc), was the principal variable measured in the ECG. By either route, there was a maximum plasma level after 1 hour, which had decreased to a minimum at 3 hours, followed by a second peak at 4 to 10 hours (orally〉iv). From 10 to 72 hours the concentrations decreased with a median t 1/2 of 23.3 hours (iv) and 33.0 hours (orally). Comparison of the ratio of plasma concentrations following oral and iv administration resulted in a bioavailability of 69 % using the 48 hour plasma levels, and 59 % using the areas under the concentration-time curves. The mean QTc was maximally shortened to 28 msec at 1 hour after iv and to 19 msec at 10 hours after the oral dose. A distinct similarity between time-concentration and time-QTc curves was seen after the initial distribution phase, both after oral and intravenous administration. The new derivative shows a rapid elimination. Its bioavailability is reasonably high.
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  • 39
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    European journal of clinical pharmacology 16 (1979), S. 417-421 
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; bioavailability ; rapidly dissolving tablet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of a rapidly dissolving tablet of theophylline and three brands of standard aminophylline tablets was estimated in a four way cross-over study involving 8 healthy adult volunteers. The relative extent of bioavailability as assessed by the measurement of the total area under the plasma concentration time curves showed no difference between the products (P〉0.05). Computed estimates of the rate of drug absorption were similar for all 4 products tested. The results indicate that the rapidly dissolving tablet offers no advantage in respect to rate and extent of absorption over conventional aminophylline tablets.
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  • 40
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    European journal of clinical pharmacology 12 (1977), S. 69-72 
    ISSN: 1432-1041
    Keywords: Metronidazole ; serum concentration ; bioavailability ; food intake ; healthy subjects ; Crohn's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possible influence of food intake on the bioavailability of metronidazole was examined in ten healthy volunteers by administration of a single dose of metronidazole on an empty stomach, and with a standardized breakfast. Food intake did not significantly alter the bioavailability of metronidazole. The interindividual variation in bioavailability appeared to be slight. In nine patients with Crohn's disease, the absorption of metronidazole appeared to be reduced and to be more variable than in healthy subjects. In both groups there was a clear relationship between the amount absorbed and dose/kg body weight. Thus, from the pharmacokinetic point of view, metronidazole can safely be given either with or between meals. The dose should be related to body weight.
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  • 41
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    European journal of clinical pharmacology 12 (1977), S. 285-290 
    ISSN: 1432-1041
    Keywords: Phenytoin acid ; phenytoin calcium ; bioavailability ; inequivalence of generics ; normal subjects ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum phenytoin concentrations have been studied in epileptic patients and healthy subjects taking tablets of phenytoin calcium (Desitin), A, phenytoin acid (Desitin), B, and phenytoin acid (Nordmark), C. Retrospective data and prospective investigation of hospitalized patients on long-term phenytoin treatment showed that significantly higher serum concentrations of phenytoin were produced by the phenytoin acid preparations B and C than by the phenytoin calcium preparation A. In a cross over study six volunteers received 200 mg/day of preparations A, B, and C for three weeks. In this study, too, higher phenytoin serum concentrations were produced by B and C than by A, although the differences were not statistically significant. The reasons for the discrepancies between the studies in healthy and epileptic subjects are discussed.
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  • 42
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    European journal of clinical pharmacology 12 (1977), S. 383-386 
    ISSN: 1432-1041
    Keywords: Benzodiazepine ; temazepam ; pharmacokinetics ; bioavailability ; hard and soft gelatine capsules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of temazepam were determined in healthy subjects after single oral administration of soft and hard gelatin capsules, and after 7 consecutive night-time doses in soft capsules. Absorption from soft gelatin capsules was significantly faster and produced earlier and higher peak plasma levels. The two pharmaceutical forms did not show any significant difference in relative availability. The apparent half-life of temazepam after night-time administration was significantly shorter than after morning administration, but no change in half-life was observed between the first and seventh night-time doses.
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  • 43
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    European journal of clinical pharmacology 14 (1978), S. 253-259 
    ISSN: 1432-1041
    Keywords: Pseudoephedrine ; side effects ; bioavailability ; multiple oral dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dose tolerance and pharmacokinetic studies of pseudoephedrine sustained action capsules were performed in thirty-three adult male subjects who received either 120 mg or 150 mg capsules every twelve hours for seven consecutive days in a double-blind parallel design study. Although only one subject in the 150 mg group was discontinued prematurely from this study, a large number of side effects typical of CNS stimulation were seen. A placebo effect might account for a portion of these complaints, however symtoms evaluated as being due to drug were significantly more severe and persistent in the 150 mg group. Pulse rates showed a persistent and significant increase while systolic and diastolic blood pressure fell from the baseline values in both groups. A pharmacokinetic analysis of the pseudoephedrine plasma concentration-time data provided estimates of half-life and the volume of distribution/availability ratio. The values obtained were in good agreement with values reported by others. Half-life was not influenced by urine pH probably as a result of the narrow range of urine pHs observed in the subjects. Calculations of relative bioavailability suggest that the 120 mg capsule formulation has a 30% greater bioavailability compared to the 150 mg capsule.
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  • 44
    ISSN: 1432-1041
    Keywords: chlorthalidone ; pharmacokinetics ; oral and i.v. doses ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven normal human volunteers each received a constant-rate infusion of chlorthalidone for 2 h, and the same (commonly 50 mg) single oral dose on separate occasions. The concentration of unchanged chlorthalidone was analyzed over a 100 to 220 h period in plasma, red blood cells, urine and faeces after both dosage forms. A three compartment model was required to describe the intravenous plasma concentrations in five of the subjects. A two compartment model sufficed to account for the decay of the oral plasma concentrations in all seven subjects. The mean plasma t1/2 after i.v. dosing was 36.5 h (±10.5 SD), and the mean plasma t1/2 after oral doses was 44.1 h (±9.6 SD). The mean red blood cell concentration t1/2 after i.v. doses was 46.4 h (±9.9 SD), and the mean red blood cell t1/2 after the oral doses was 52.7 h (±9.0 SD). The shorter i.v. half-live was not equally manifest in all subjects, being mainly apparent in three of them. In all cases the urinary excretion rate plots were parallel to the plasma concentration curves. As the faster decay after i.v. administration was not accompanied by increased renal clearance, the difference must have been due to non-renal mechanism. The mean total of 65.4 (±8.6 SD) % of the intravenous dose was excreted in urine over infinite time, whereas the mean total excretion after the oral dose was 43.8 (±8.5 SD) %. Faecal excretion ranged from 1.3–8.5% of dose in the i.v. study to 17.5–31.2% of dose in the oral study. The sum of the amounts present in urine plus faeces pointed strongly to an important metabolic route of elimination of chlorthalidone. Bioavailability estimates (F) from three sets of data were — a mean F of 0.61 from plasma concentrations, 0.67 from urinary excretion measurements and 0.72 from the erythrocyte concentrations. Simulations with a non-linear model indicated lesser validity of the estimate from erythrocyte concentrations. It was concluded that the average of plasma and urine data, F=0.64, yielded the best estimate of the oral availability of chlorthalidone 50 mg in man.
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  • 45
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    European journal of clinical pharmacology 16 (1979), S. 31-38 
    ISSN: 1432-1041
    Keywords: bezafibrate ; hyperlipoproteinemia ; bioavailability ; pharmacokinetics ; GC-MS
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition kinetics of bezafibrate, a newly developed drug of great lipid-lowering potency, were investigated in normal male subjects. Five male volunteers received14C-labelled bezafibrate orally in solution, and a further 10 were given the same dose (300 mg) of un-labelled drug as tablets. The concentration of bezafibrate in serum and urine from the latter was determined by GC, and in the former total radioactivity in serum, urine and feces was followed for 48 h, and urinary excretion products were analysed by TLC and GC-MS. Rapid absorption from the gastrointestinal tract led to peak serum levels 30 min and 2 h after administration of solution and tablets, respectively. Since approximately 95% of the administered14C-bezafibrate was excreted in urine within 48 h, and almost all the remainder was detected in feces, absorption can be regarded as complete after administration in solution. The relative optimal bioavailability from the tablets was also complete, since in both cases approximately 50% of the administered dose was detected as unchanged bezafibrate in urine within 24 h by GC in the tablet study, and by TLC in the solution study. Of the decomposition products, more than 20% of the dose was present as glucuronides and the remainder consisted of several more polar compounds, one of which was identified as a hydroxyderivative of bezafibrate. Since the apparent halflife of bezafibrate in serum was 2.1 h, this new drug possesses favourable pharmacokinetic features: rapid and complete absorption, even from tablets, combined with a conveniently short half-life, and clearance which is half renal (56 ml/min) and half metabolic (43 ml/min), giving a total clearance of 99 ml/min.
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  • 46
    ISSN: 1432-1041
    Keywords: indobufen ; platelet aggregation ; single dose ; bioavailability ; pharmacodynamics ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy volunteers received single iv and oral doses of 2-[p-(1-oxo-2-isoindolinyl)phenyl] butyric acid 100 mg (indobufen; K 3920), an inhibitor of platelet aggregation. Plasma levels and urinary excretion of the drug were determined by GLC. Collagen-induced platelet aggregation was assessed turbidimetrically at various intervals after administration. The plasma half-life of the drug was 7–8 h and more than 70% of the administered dose was recovered within 48 h in urine, as unchanged drug and as the glucuronide of indobufen. After oral administration of tablets of two different formulations, the drug was completely absorbed, but one formulation showed faster absorption. The maximal inhibitory effect on platelet aggregation was observed 1 to 4 h after iv administration, and it had decreased by 8 h. After tablets, peak effect and the time of the peak were similar, but activity was significantly prolonged, in accordance with the higher plasma levels found at 8 h. The data suggest that the effect of indobufen on platelets is reversible, and that for this drug platelets behave as a compartment that slowly equilibrates with plasma.
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  • 47
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    European journal of clinical pharmacology 16 (1979), S. 45-48 
    ISSN: 1432-1041
    Keywords: quinidine ; slow release formulation ; pharmacokinetics ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of quinidine in two sustained release preparations A and B has been compared in three females and three males with i.v. administration of quinidine. The initial rate of oral absorption did not differ between the two drug preparations; the peak concentration was observed after 4 h both for A and B, but was significantly higher after B. A slower decrease in plasma concentration was observed after preparation A than B. Absolute bioavailability did not differ significantly between A (median value 78.4%) and B (median 87.1%). Drug absorption in vivo was in good agreement with the results of in vitro dissolution tests on both preparations. The slower decrease in plasma concentration found for the new sustained release form of quinidine should be of clinical advantage.
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  • 48
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    European journal of clinical pharmacology 10 (1976), S. 183-187 
    ISSN: 1432-1041
    Keywords: Hydralazine ; bioavailability ; pharmacogenetics ; first pass effect ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After oral administration of a single 50 mg dose of hydralazine (Apresoline®), the serum half-life (T1/2) and bioavailability (AUC0−∞) were assessed in 16 healthy volunteers. The half-life was 2.57±0.14 h (S.E.) in 10 slow acetylators of sulphadimidine, and 2.18±0.15 h in 6 fast acetylators (difference not statistically significant). AUC0−∞ was significantly higher in slow acetylators, at 1.04±0.10 µg·hour·ml−1, compared to 0.66±0.12 µg·hour·ml−1 in the fast acetylators (p〈0.025). Treatment with Apresoline® 25 mg tid produced minimum serum concentrations at steady-state of 57.3±7.3 ng·ml−1 and 33.4±4.2 ng·ml−1 in 8 slow and 5 fast acetylators, respectively (p〈0.05). The corresponding maximum concentrations were 228.8±20.3 ng·ml−1 and 147.6±15.0 ng·ml−1 in slow and fast acetylators, respectively (p〈0.025). First-pass metabolism of hydralazine could explain the difference in bioavailability of the drug between fast and slow acetylators, without any corresponding difference in the elimination rate of the drug in the post-distributive phase.
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  • 49
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    European journal of clinical pharmacology 10 (1976), S. 395-401 
    ISSN: 1432-1041
    Keywords: Hydralazine ; bioavailability ; polymorphic acetylation ; first-pass metabolism ; oral and intravenous dosing
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of orally administered hydralazine was assessed in 4 healthy subjects after separate administration of a single oral or intravenous dose (0.3 mg·kg−1). Comparison of the areas under the serum concentration-time curves showed that 26 – 55 % of the oral dose was available to the systemic circulation as unchanged drug. The O - 24 h excretion of the drug in urine was rapid: 11.4 – 14.1 % of the dose after intravenous administration, and 2.0 – 3.6 % after an oral dose. Acetylation of hydralazine leads to formation of 3-methyl-s-triazolo-3,4,a-phthalazine (MTP) and a gas-liquid-chromatographic method for its measurement in urine was developed. After oral and intravenous administration, 0.8 – 1.2 % and 1.4 – 2.3 % of the dose, respectively, were recovered within 24 hours from urine as MTP. After oral administration there was a relative increase in the amount of MTP in every subject, which indicates route-dependent metabolism. The lower bioavailability of oral hydralazine could be explained in terms of first-pass metabolism.
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  • 50
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    European journal of clinical pharmacology 16 (1979), S. 335-340 
    ISSN: 1432-1041
    Keywords: cimetidine ; enterohepatic circulation ; irregular absorption ; bioavailability ; pharmacokinetics ; volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of cimetidine have been studied in healthy volunteers after administration of single intravenous (100 mg) and oral doses (100, 400 and 800 mg). After i.v. administration, the kinetics of cimetidine could be described by a linear, two compartment open model. Substantial variation in half-life was observed between subjects, with a mean value of 2.1 h (range 0.9–4.7). Cimetidine had a low hepatic extraction ratio and a high total plasma clearance, due to extensive urinary excretion of unchanged drug. After oral administration, the plasma concentration vs time curves in most subjects exhibited two marked peaks, an observation that seemed to be constant within individuals and was independent of dose. Bioavailability, estimated as the area under the plasma concentration vs time curves (AUC), after oral doses as compared to the intravenous dose, in most cases exceeded 100%. There was no correlation between bioavailability estimated as AUC and as urinary excretion of unchanged drug. These observations may indicate an enterohepatic circulatory mechanism, predominantly after oral administration. Both unchanged drug and its sulphoxide metabolite appear to be excreted in bile. The latter was shown in vitro to be reduced to cimetidine by fecal bacteria.
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  • 51
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    European journal of clinical pharmacology 13 (1978), S. 267-274 
    ISSN: 1432-1041
    Keywords: Chlordiazepoxide ; benzodiazepines ; pharmacokinetics ; bioavailability ; intramuscular injection ; alcohol withdrawal
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of oral and intramuscular (i. m.) chlordiazepoxide hydrochloride (CDX · HCl) was compared in two pharmacokinetic studies. In Study One, single 50-mg doses of CDX · HCl were administered orally and by i. m. injection to 14 healthy volunteers using a crossover design. Whole-blood concentrations of chlordiazepoxide (CDX) and its first active metabolite, desmethylchlordiazepoxide (DMCDX), were determined in multiple samples drawn after the dose. Mean pharmacokinetic variables for CDX following oral and i. m. administration, respectively, were: highest measured blood concentration, 1.65 vs 0.87 µg/ml (p〈0.001); time of highest concentration, 2.3 vs 7.6 h after dosing (p〈0.001); apparent absorption half-life, 0.71 vs 3.39 h (p〈0.001). Biphasic absorption after i. m. injection, consistent with precipitation at the injection site, was observed in 9 of 14 subjects. Based upon comparison with previous intravenous data, the completeness of absorption was 100% for oral vs 86% for i. m. CDX · HCl (p〈0.1). In Study Two, 28 male chronic alcoholics with clinical manifestations of the acute alcohol withdrawal syndrome were randomly assigned to one of four treatment conditions: 50 or 100 mg doses of CDX · HCl, by mouth or by i. m. injection. Concentrations of CDX and DMCDX, determined in plasma samples drawn every 20 min for 5 h following the dose, were significantly higher after oral administration of a given dose than at corresponding points in time after i.m. injection after the same dose. Thus absorption of oral CDX is reasonably rapid and complete, whereas the absorption rate of i. m. CDX is slow.
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  • 52
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    European journal of clinical pharmacology 15 (1979), S. 269-274 
    ISSN: 1432-1041
    Keywords: phenytoin ; food-intake ; bioavailability ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the absorption of phenytoin was examined in eight healthy volunteers, by study of single-dose kinetics following ingestion of phenytoin 300 mg either with a standardized breakfast or on an empty stomach. Blood samples were collected at regular intervals from 0 to 48 h, and serum concentrations of unmetabolized phenytoin were determined by gas chromatography. Serum concentrations of the major metabolite of phenytoin, 4-hydroxyphenytoin, were measured by mass fragmentography. Concurrent intake of food and phenytoin appeared to accelerate absorption of the drug from the formulation used, and the peak concentrations were significantly higher (mean increase 40%) in the postprandial than in the preprandial state. As reflected by the AUC (area under the curve), the amount of drug absorbed was increased during postprandial conditions, although the difference only reached borderline significance. It is suggested that phenytoin should always be taken in a defined relation to meals.
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  • 53
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    European journal of clinical pharmacology 16 (1979), S. 107-112 
    ISSN: 1432-1041
    Keywords: quinidine ; enteric-coated tablets ; bioavailability ; gastric emptying ; pH
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of quinidine from single and multiple doses of an enteric-coated preparation (Systodin®) was studied in seven healthy subjects, and was compared with the pharmacokinetics of intravenously administered quinidine and the results of in vitro dissolution tests of the tablets. Absorption of quinidine began after a variable delay, 2–8 h (mean 4.8) after fasting and 3–10 h (mean 6.1) after food. The rate of absorption varied both in and between individuals. It appeared to be lower when the drug was administered after food. Multiple doses after food gave a pattern of plasma concentration-time curves similar to that found on administration of single doses after food. The delay prior to absorption was prolonged at night. The ratio between the maximum and minimum concentration of quinidine during a dose interval varied from 1.3 to 3.2 (mean 2.0). Bioavailability of quinidine in fasting subjects ranged from 69 to 95% (mean 83); variation was greater when doses were administered after food. The release of quinidine from the enteric-coated preparation was pH dependent and was sustained at low pHs as may be found in the intestines. The results indicate that the absorption of quinidine from the enteric-coated formulation was dependent on the highly variable rate of gastric emptying and the pH of intestinal fluid, and it varied greatly both within and between individuals.
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  • 54
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    European journal of clinical pharmacology 16 (1979), S. 141-147 
    ISSN: 1432-1041
    Keywords: prazepam ; N-desmethyldiazepam ; bioavailability ; pharmokinetics ; electron-capture gasliquid chromatography
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An original electron-capture gas chromatographic assay was developed for simultaneous measurement of plasma levels of the benzodiazepine derivative prazepam and of its principal unconjugated metabolite, N-desmethyldiazepam. The assay was used to study the pharmacokinetics of the drug and its comparative bioavailability from tablets and from a specially prepared solution. Nine healthy adult volunteers were studied. Each volunteer on one occasion took 30 mg of the drug in tablet form, and on another occasion 30 mg of the drug in solution. In all subjects, N-desmethyldiazepam appeared in plasma shortly after prazepam appeared and reached a peak within four hours of prazepam ingestion. Thereafter plasma N-desmethyldiazepam levels were much higher than plasma prazepam levels throughout. Prazepam became undetectable within six hours of intake, whereas its metabolite could still be measured in plasma fourteen days after dosage. Thus much of the pharmacological action of prazepam may be mediated through its metabolite, N-desmethyldiazepam. In five of the nine subjects, areas under the plasma level curves for the metabolite were not markedly different for the tablet and solution formulations studied. In the other four subjects the area under the curve for the tablets was 50% to 80% of the area under the curve for the solution. The time to reach peak plasma level for the metabolite was shorter after the solution formulation (mean 2.0±SD 1.2 h) than after the tablet formulation (mean 4.2±SD 1.7 h).
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  • 55
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    European journal of clinical pharmacology 10 (1976), S. 55-58 
    ISSN: 1432-1041
    Keywords: Penicillin V ; bioavailability ; pharmacokinetics ; dose ranging
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An absorption study was performed in ten healthy volunteers to test the bioavailability of various doses of two penicillin V-K preparations: Isocillin® (Hoechst AG, Federal Republic of Germany), — tablets of 600 000 and 1.2 Mega U; V-Cillin® (Eli Lilly, USA), — tablets of 200 000, 400 000 and 800 000 U. The serum concentrations and elimination of the active substance in urine were measured for six hours after administration. Independently of the source of the preparation, a strict linear relation between the dose and the area under the serum curve (AUC), or between the dose and the urinary elimination, was demonstrated by regression analysis. The dose-dependent increase in the AUC was highly significant (p〈0.01) in the range tested, i.e. between 200 000 and 1.2 Mega U. The relative elimination of active substance in urine lay within narrow limits for all doses (35.7–41.3%). Thus, both compounds proved to have the same bioavailability.
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  • 56
    ISSN: 1432-1041
    Keywords: Ampicillin ; bioavailability ; pharmacokinetics ; branded products ; proprietary preparations ; capsule formulation ; tablet formulation
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of three different brands of ampicillin were studied in 10 volunteers. After intravenous administration ampicillin can be described adequately by a two-compartment open pharmacokinetic model. The half-life during the α-phase was 9 min and the β-half-life was in the range 50–60 min, independent of the mode of administration. Absolute bioavailability was determined from the ratio of the areas under the serum concentration curves obtained after oral and intravenous administration of equal doses. Bioavailability was also estimated by analysis of variance. The results indicated absolute availability of the three products of 39–54%. One of the products, a capsule formulation, showed a significantly lower bioavailability than the others, which were tablet formulations.
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  • 57
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    European journal of clinical pharmacology 11 (1977), S. 277-281 
    ISSN: 1432-1041
    Keywords: Proscillaridin ; oral administration ; portal venous sample ; porto-peripheral concentration difference ; bioavailability ; 86Rb-uptake inhibition assay
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of proscillaridin A was studied in four patients undergoing catheterization of the portal vein for diagnostic purposes. Proscillaridin 1.5 mg was given as a single oral dose and plasma glycoside activity was analyzed by the86Rb-uptake inhibition technique. Proscillaridin appeared rapidly in the portal blood, peak activity being found after 15 min in three and after 30 min in one patient. In peripheral blood the peak activity occurred after approximately 35 min. Despite rapid passage across the gut wall, porto-peripheral differences in glycoside activity were small; they were zero after 4 h. The mean amount absorbed as active proscillaridin during the first 4 h after the dose was calculated to be only 7.1% of the given amount. Late porto-peripheral differences, probably due to enterohepatic recycling, appeared after 6 h in three patients. The results suggest that proscillaridin undergoes first pass inactivation in the gut wall. Enterohepatic recirculation may contribute to the amounts of active glycoside that reach the systemic circulation.
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  • 58
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    European journal of clinical pharmacology 10 (1976), S. 49-54 
    ISSN: 1432-1041
    Keywords: Three-compartment open model ; intravenous infusion ; apparent volume of distribution ; renal insufficiency ; miconazole ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic profile of miconazole has been studied in normal subjects and in patients suffering from severe renal insufficiency; one group of patients was undergoing intermittent haemodialysis. A three-compartment open model was fitted to the observed plasma concentrations obtained after intravenous infusion of miconazole 522 mg over fifteen minutes. The rate constants of elimination and exchange between compartments computed for the three groups were not significantly different. The apparent volumes of distribution in the cases of renal failure not undergoing haemodialysis were significantly smaller than the corresponding control values. A computational procedure is described which reduces observations obtained after infusion to the case of a single rapid intravenous administration.
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  • 59
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    European journal of clinical pharmacology 11 (1977), S. 207-212 
    ISSN: 1432-1041
    Keywords: Chlorpropamide ; hypoglycaemic agent ; bioavailability ; plasma concentrations ; bioequivalence ; dissolution tests
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of chlorpropamide from two new formulations (Melitase® tablets) has been compared to that from a reference formulation which is currently in clinical use as a hypoglycaemic agent. In both rate and extent of bioavailability, all three formulations may be considered equivalent, providing allowances are made for differences in drug content. With 95% confidence, the mean bioavailability of chlorpropamide from the new formulations was within about 16% of the mean from the reference formulation, and formulation-related differences were not statistically significant. Although all three formulations were shown to have similar dissolution profiles, dissolution of chlorpropamide was pH-dependent in vitro. Dissolution was almost complete during 30 min at pH 7.2, but only 40%–60% had dissolved during 90 min at pH 2.0. A peak mean concentration of 22.7 µg/ml was reached 3 h after administration of 2×100 mg tablets of the new formulation and peak mean concentrations of 26.8 µg/ml and 27.4 µg/ml were reached 3 h and 4 hours after administration of one 250 mg tablet of the new formulation and one 250 mg tablet of the reference formulation respectively. Formulation-related differences of mean plasma concentrations (after scaling for equal doses of 250 mg) were not significant and each formulation provided similar plasma concentrations at corresponding times after administration. Statistically significant subject-related differences in all the parameters of bioavailability were shown by analyses of variance.
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  • 60
    ISSN: 1432-1041
    Keywords: ergotamine ; migraine ; bioavailability ; radioimmunoassay ; plasma level ; CSF level ; continuous dosing
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma ergotamine concentrations were determined by radioimmunoassay in 10 healthy subjects after a 2 mg oral dose of ergotamine, administered at 24 h intervals on three consecutive days. After the first dose the mean peak plasma level of 0.35±0.05 (SEM) ng/ml was found 1–2 h after administration. In the samples obtained 2 h after the second and third doses, plasma ergotamine levels did not exceed the first peak value. On the other hand, after the third and last dose the plasma ergotamine began to rise slowly, reaching maximum of 0.70± 0.10 ng/ml on the 6th day after administration. This supports the concept of accumulation of the drug or of immunoreactive metabolites. CSF ergotamine was determined in 4 patients, who underwent lumbar puncture for other diagnostic purposes, 1 to 2 h after the 2 mg oral dose. A concentration of 0.40± 0.03 ng/ml was observed. In seven out of 18 migraine patients who were taking ergotamine preparations daily (mean 11.7 mg/week), ergotamine could not be detected in plasma 1 h after administration of the dose. In the remaining migraine patients, the pattern of plasma ergotamine after both the daily and the test doses was similar to that of the 10 healthy subjects. The results in volunteers and migraine patients suggest notable variation in bioavailability of the drug. It seems that in most subjects there is accumulation or tissue redistribution of ergotamine or its immunoreactive metabolites, although in a significant number of migraine patients who use the drug daily, ergotamine does not appear to be biologically available.
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  • 61
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    European journal of clinical pharmacology 16 (1979), S. 405-410 
    ISSN: 1432-1041
    Keywords: diclofenac ; plasma levels ; intravenous bolus administration ; oral administration ; enteric coating ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of diclofenac were examined following single rapid intravenous injection and also following single oral doses to healthy female volunteers. After intravenous injection plasma levels of diclofenac fell rapidly and were below the limits of detection at 5.5 h postdosing. Individual drug profiles were described by a triexponential function and mean half-lives of the three exponential phases were 0.05, 0.26 and 1.1 h. After oral doses of enteric-coated tablets, the lag time between dosing and the appearance of drug in plasma varied between 1.0 and 4.5 h. However once drug absorption had commenced similar plasma drug profiles were obtained in different individuals. Peak plasma diclofenac levels ranged from 1.4 to 3.0 µg · ml−1. The mean terminal drug half-life in plasma was 1.8 h after oral doses. This value was not significantly greater than the value of 1.1 h following intravenous doses. Fifty percent of orally dosed diclofenac did not reach the systemic circulation due, predominantly, to first-pass metabolism.
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  • 62
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    European journal of clinical pharmacology 11 (1977), S. 219-224 
    ISSN: 1432-1041
    Keywords: Nortriptyline ; 10-OH-nortriptyline ; bioavailability ; plasma metabolites ; first pass metabolism ; oral dose ; intramuscular dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nortriptyline was given orally and intramuscularly to six depressed patients. Plasma concentrations of parent drug and the unconjugated and conjugated principal metabolite, 10-hydroxynortriptyline, were determined by mass fragmentography. There was a significant decrease in the area under the nortriptyline plasma concentration — time curve after the oral route of administration, whilst the elimination rate was unchanged. With the oral dose, plasma concentrations of the metabolites were higher and peaked earlier than after intramuscular administration, whilst the opposite was true for the parent compound. This proves that the difference in bioavailability between the two routes of administration was due to first pass metabolism. As determined from the ratio between corresponding areas, the relative bioavailability of the oral dose was 66±21 S.D. per cent. This fraction is higher than that reported previously when intravenous nortriptyline was used as the reference dosage form.
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  • 63
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    European journal of clinical pharmacology 12 (1977), S. 281-284 
    ISSN: 1432-1041
    Keywords: Tetracycline ; bioavailability ; plasma levels ; nutritional state ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Relative bioavailability after oral administration of a single dose and Cmin levels of tetracycline in plasma after multiple doses were determined in groups of well-nourished and undernourished subjects. The relative bioavailability of tetracycline, assessed by the area under serum concentration time-curves, did not differ in undernourished and well-nourished patients. The plasma levels were not different in the two groups after the conventional dose of tetracycline HCl 250 mg at 6 hour intervals. However, in these studies undernourished subjects received a higher dose per kg body weight, which could have compensated for any effect of a shortened half life of the drug. When the dose per kg body weight was reduced, the Cmin levels were lower. On the other hand, with the same dose per kg body weight at more frequent intervals, the plasma concentrations were similar to those in well-nourished subjects. These studies indicate that the dosage regimen should be based both on body weight and on the nutritional status of the individual.
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  • 64
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    European journal of clinical pharmacology 12 (1977), S. 65-68 
    ISSN: 1432-1041
    Keywords: Indomethacin ; antacids ; drug-drug interactions ; bioavailability ; drug combinations
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The biovailability of indomethacin from two indomethacin-antacid (aluminum hydroxide magnesium carbonate and magnesium hydroxide) combinations was compared with the bioavailability of oral indomethacin. Relative bioavailability was estimated by three methods: comparison of plasma concentrations at various times, comparison of areas under plasma concentration time curves, and comparison of the amount of drug excreted unchanged in the urine. A double blind three-way crossover study was conducted in twelve healthy volunteers. The combination with the slightly smaller amount of antacid (preparation A) showed significantly decreased bioavailability by all three methods in comparison with indomethacin alone (preparation C). The combination with the larger amount of antacid (preparation B) was also less bioavailable than preparation C. This effect was significant only for the comparison of areas under curves and not for plasma levels, although the mean plasma levels produced by preparation B at all times were lower than those for preparation C. These findings suggest that aluminum hydroxide magnesium carbonate and magnesium hydroxide decrease the bioavailability of indomethacin.
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  • 65
    ISSN: 1432-1041
    Keywords: Tolmetin ; pharmacokinetics ; bioavailability ; antacid ; oral dose
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The purpose of this study was to determine whether a concomitant single dose of antacid or multiple doses of antacid administered prior to, and with tolmetin, alter the pharmacokinetics of tolmetin when the drug was administered as a commercially available tablet containing tolmetin sodium. The possible effects of the antacid on plasma concentrations and urinary excretion of tolmetin and its major metabolite were evaluated following administration of: (a) tolmetin sodium alone; (b) antacid four time a day for three days prior to a single dose of tolmetin sodium, with continuation of the antacid during the day tolmetin was given; and (c) co-administration of single doses of tolmetin sodium and antacid. The twenty-four subject study was of the crossover type. There were no significant differences among treatment means for: (i) peak plasma concentrations of both tolmetin and metabolite, (ii) AUC 0–8 h and AUC 0-∞ for both tolmetin and metabolite, (iii) time to peak plasma concentration for both tolmetin and metabolite, (iv) plasma concentrations of both tolmetin and the metabolite at all sampling times (except for tolmetin at 2 h), (v) renal clearance of both tolmetin and its metabolite, and (vi) the amount of metabolite excreted in the 0–24 h urine. There were small, but significant, differences among amounts of tolmetin excreted in the 0–24 h urine. Semilogarithmic plots of both tolmetin and metabolite plasma concentrations past the peak concentrations were curved over the entire 8-h observation period; although the elimination half-life of tolmetin has been reported to be about one hour, the half-life most probably exceeds 2.6 h in most subjects. The results of this study indicate a lack of a significant drug-drug interaction between the non-steroidal anti-inflammatory agent, tolmetin sodium, and a commonly used antacid, which is a mixture of magnesium and aluminium hydroxides.
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  • 66
    ISSN: 1432-1041
    Keywords: Coumarin ; 7-Hydroxycoumarin ; drug disposition ; first-pass effect ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of coumarin (C) upon i.v. and p.o. administration and its metabolites 7-hydroxy-coumarin (7-HC) and 7-hydroxy-coumarin glucuronide (7-HCG) have been studied. Six healthy volunteers were involved in this investigation. Four of the volunteers participated in a crossover study. Coumarin was administered i.v. and p.o. in dose sizes of 0.25 mg/kg and 0.857 mg/kg, respectively. Coumarin is rapidly absorbed p.o., however the availability to systemic circulation is less than 4%. The rest of the dose appears quantitatively as 7-HC and 7-HCG in systemic circulation suggesting an extensive firstpass effect. Coumarin and 7-HCG are best fitted to an open two-compartment model, whereas 7-HC is best fitted to an open one-compartment model. The biological half-life of both C (0.80 vs. 1.02 h) and 7-HCG (1.47 vs. 1.15 h) was not significantly different for the two routes of administration. The large total clearance of C again suggests a first-pass effect; while that of 7-HCG, which is nearly exclusively eliminated into urine, indicates active tubular secretion of the glucuronide.
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  • 67
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    European journal of clinical pharmacology 13 (1978), S. 35-39 
    ISSN: 1432-1041
    Keywords: Norethindrone ; bioavailability ; man ; competitive protein binding ; sex differences ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.
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  • 68
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    European journal of clinical pharmacology 14 (1978), S. 261-265 
    ISSN: 1432-1041
    Keywords: Procainamide ; slow release formulations ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Procainamide was given to 20 patients with normal renal function as an i.v. bolus of 500 mg followed by 1.0 or 1.5 g eight-hourly by mouth in the form of a slow release preparation (Durules). 97.6±27.1 (SD)% of the oral procainamide was absorbed, the absorption half life being 1.54 h. The elimination half life following the oral formulation was 6.0±0.8 h, compared to a mean of 3.4±0.4 h following i.v. administration. Elimination half life following i.v. administration was slightly related to acetylator status, being 2.75±0.9 h in fast acetylators, and 4.4±2.4 h in slow acetylators. This dependence on acetylator status was not seen in half life following oral administration. Total body clearance, steady state plasma procainamide and N-acetylprocainamide were not significantly dependent on acetylator status, although a few patients who are slow acetylators had unexpectedly low clearance and high steady state procainamide concentrations when given the higher dose.
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  • 69
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    European journal of clinical pharmacology 14 (1978), S. 357-360 
    ISSN: 1432-1041
    Keywords: Lanoxin tablets ; Lanoxicaps ; sorbitol ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary (1) The mean cumulative urinary digoxin excretion over 8 days was compared in 8 healthy volunteers after single doses of digoxin administered as 3 Lanoxin tablets of 0.25 mg, 3 digoxin tablets of 0.2 mg, 12 Lanoxicaps without sorbitol of 0.05 mg, 6 Lanoxicaps without sorbitol of 0.1 mg digoxin, 3 Lanoxicaps without sorbitol of 0.2 mg and 3 Lanoxicaps with sorbitol of 0.2 mg. (2) There was no significant difference between the 8 day cumulative urinary excretion for any of the Lanoxicaps treatments. (3) Cumulative urinary excretion after 3 digoxin tablets of 0.2 mg was significantly (P〈0.05) lower than after all other treatments. (4) Cumulative urinary excretion after 3 Lanoxin tablets of 0.25 mg was not significantly different from that after any of the Lanoxicaps treatments except 0.1 mg Lanoxicaps without sorbitol, it was significantly (P〈0.05) lower after the latter. (5) Mean urinary excretion of digoxin was 60% of ingested dose for all Lanoxicaps treatments and was significantly (P〈0.05) higher than the mean value of 50% for both tablet treatments. (6) Enhanced absorption of digoxin from Lanoxicaps was confirmed and shown to be unrelated to the sorbitol content of the capsule shell.
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  • 70
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    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 255-280 
    ISSN: 1573-8744
    Keywords: biliary recycling ; bioavailability ; biotransformation ; clearance ; route dependence ; enterohepatic circulation ; indomethacin
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    Topics: Chemistry and Pharmacology
    Notes: Abstract There are no discernible quantitative differences in the biotransformation and the excretion of indomethacin following oral, rectal, and intravenous administration of indomethacin-14 C. Approximately 50% (range 24–115% for n=6) of an intravenous dose undergoes enterohepatic circulation. Thus the bioavailability of indomethacin to the systemic circulation may exceed the administered dose. Relative to the intravenous dose, indomethacin is 80 and 100% bioavailable from suppositories and capsules, respectively. Absorption and/or reabsorption appears to be more rapid and uniform by the rectal route. Recognition of the attributes of biliary recycling also helps to explain the observed variability in apparent plasma half-life, while their neglect requires alternative explanations for anomalies between the disappearance rate from plasma and the corresponding appearance rate in urine.
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  • 71
    ISSN: 1573-8744
    Keywords: accelerated convergence method to estimate AUC0-∞ and A e ∞ ; bioavailability ; estimation of total areas ; estimation of total amounts excreted ; blood sampling schemes for digoxin ; elimination half-life of digoxin ; intra- and interindividual variation of renal clearance of digoxin
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Five methods are compared to estimate the total area under the digoxin plasma or serum concentrationtime curve (AUC0-∞) after a single dose of drug. To obtain accurate estimates of AUC0-∞, data required are concentrations at a sufficient number of sampling times to define adequately the concentration-time curve prior to the log-linear phase, and at least three, but preferably four or more equally spaced points in the terminal loglinear phase. One method (designated Method I) requires a digital computer; another (Method III) is the classical method (these two methods do not require equally spaced points in the loglinear phase). Method IIA is the accelerated convergence method of Amidon et al.; Methods IIB and IIC are modifications of this method, but incorporate usual and orthogonal least squares, respectively, which make them more accurate with real (noisy) data. Methods I and IICgave very comparable estimates of AUC0-∞. Results indicate that digoxin administered orally in aqueous solution was completely (100%) absorbed when bioavailability estimates were based on oral and intravenous AUC0-∞ estimates and the actual doses, whereas formerly only about 80% absorption was reported, based on areas, under plasma concentration curves which were truncated at 96 hr. It is shown that the sampling scheme of blood can produce biased apparent bioavailability estimates when areas under truncated curves are employed, but an appropriate sampling scheme and application of method IIyield accurate bioavailability estimates. This is important particularly in those bioavailability studies where one is attempting to determine the appropriate label dose for a new “fastrelease” digoxin preparation relative to the label dose and bioavailability of currently marketed tablets. It is shown that the magnitudes and variability of apparent elimination rate constants and halflives of digoxin, estimated from urinary excretion data by the σ− method, depend on which value of A e ∞ is used. The formerly reported greater interindividual variability of AUC data compared to At data for digoxin is explained in that the AUCs, but not the Ae,'s, involve the renal clearance, which exhibits considerable inter- and intraindividual variation.
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  • 72
    ISSN: 1573-8744
    Keywords: quinidine ; pharmacokinetic parameters ; assay methods ; assay specificity ; area under the plasma concentration-time curve ; bioavailability ; clearance ; therapeutic window
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Previously published estimates of pharmacokinetic characteristics of quinidine can be shown to be dependent on whether the investigators have used analytical methods which are specific for quinidine. Areas under the plasma concentration-time curve and peak plasma concentrations after administration of the drug were higher and clearance values consequently lower in studies utilizing nonspecific assays unable to distinguish quinidine from its metabolites. The error introduced is larger after oral administration as a result of marked first-pass metabolism of quinidine. The absolute oral bioavailabilities from pharmaceutical preparations might therefore be estimated higher in studies with assays including metabolites in the determination. Although the pharmacodynamic response to quinidine is related to the plasma concentration, the therapeutic window of drug concentrations has been defined only using nonspecific assays. In light of the availability of newly developed specific assays, redefinition of the range of therapeutic plasma concentrations is opportune.
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  • 73
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    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 265-282 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; linear systems analysis ; in vivo dissolution rates ; absorption rates ; metabolic rates ; bioavailability ; numerical desconvolution
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The application of certain aspects of linear systems analysis to pharmacokinetic-problems is described. Topics covered include the evaluation of in vivodissolution rates, absorption rates, and metabolic rates, and the use of pharmacological data. Relevant numerical procedures are also discussed.
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  • 74
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    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 337-353 
    ISSN: 1573-8744
    Keywords: bioavailability ; pharmacological data ; pharmacokinetics ; modeling
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The use of data deriving from monitoring the time variation of the intensity of pharmacological effect(s) following dosing can often present an advantageous alternative to the more conventional approach of using chemical or radiological assay of blood and/or urine level data for bioavailability evaluations of drug products: bioavailability studies can be performed with drugs where no assay exists. A relatively simplified discussion of the general theoretical principles on which the use of pharmacological data is based and a stepwise description of the approach for its routine application in bioavailability studies are presented. Approaches for computing rates and extents of drug bioavailability vs. time profiles on analog and digital computers are qualitatively described and quantitatively presented in a subsequent report. The concept of preabsorption (gastrointestinal bioavailability) is introduced and biophasic availability of drugs to local sites of action is discussed.
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  • 75
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    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 355-375 
    ISSN: 1573-8744
    Keywords: deconvolution ; bioavailability ; pharmacokinetics ; modeling ; pharmacological data
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Mathematical expressions and approaches to the computation of rates and extents of drug bioavailability for implementation on analog and digital computers are derived. The equivalency of expressions derived on the basis of assuming compartment models to an approach based on using experimentally determined weighting functions is demonstrated. The relative merits of the two techniques are discussed: their application for use with temporal pharmacological data is emphasized. The applicability of the computational techniques to determining the availability of drugs at local sites of action (biophasic availability) and to computing preabsorptive drug release into the gastrointestinal contents (gastrointestinal bioavailability) is pointed out. An approach to computationally predicting in vivo blood level or pharmacological response vs. time profiles from in vitro dissolution testing results is presented and its limitations are discussed.
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  • 76
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 429-451 
    ISSN: 1573-8744
    Keywords: ampicillin ; bacampicillin ; pivampicillin ; prodrug ; bioavailability ; zero-order absorption ; two-compartment model ; renal clearance
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Five healthy fasting male subjects were each given single doses of intravenous ampicillin (471 mg), oral ampicillin tablets (495 mg), oral bacampicillin hydrochloride tablets (562 mg ampicillin equivalent), and oral pivampicillin hydrochloride capsules (491 mg ampicillin equivalent) in a crossover experiment. The resulting concentrations of ampicillin were determined in plasma and urine. The pharmacokinetic analysis was made according to a two-compartment open model. The total distribution volume of unbound ampicillin during the disposition phase was 0.247 ± 0.045 (sd) liter/kg, which is only slightly more than the extracellular fluid, suggesting that tissue binding and intracellular distribution of ampicillin are limited. The bioavailability of the esters bacampicillin (86 ± 11%) and pivampicillin (92± 18%) was significantly greater than that of ampicillin (62 ± 17%); however, the difference between the esters was not statistically significant. The absorption for all drugs given orally proceeded at a constant rate, suggesting zero-order release rates from the products. The absorption rate was highest for bacampicillin (0.89 ± 0.39% of dose absorbed per minute), followed by pivampicillin (0.64 ± 0.19) and ampicillin (0.58 ± 0.16). Bacampicillin also had the shortest lag time for the start of absorption (7.0 ± 0.9 min) under the present conditions. Thus, in comparison with ampicillin, the esters have a higher bioavailability, which, in fact, is close to the theoretically highest possible value by clearance concepts. The higher bioavailability in connection with higher absorption rates may be clinically important in ampicillin treatment by the oral route.
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  • 77
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    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 327-336 
    ISSN: 1573-8744
    Keywords: bioavailability ; phenytoin ; capacity-limited elimination
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The bioavailability of phenytoin, a drug subject to capacity-limited disposition, was examined using linear and nonlinear pharmacokinetic techniques. The linear method (comparative areas) underestimates the essentially complete bioavailability of this drug from capsules (Epanutin, Parke-Davis). The error incurred in using area ratios is inversely related to the rate of absorption of the drug. The time course of absorption of phenytoin capsules is irregular and prolonged over nearly 2 days.
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  • 78
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    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 521-535 
    ISSN: 1573-8744
    Keywords: carbamazepine ; single and repeated oral doses in healthy humans ; pharmacokinetic profile ; bioavailability ; enzymatic induction ; computer calculation of the elimination rate changes during treatment
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetic profile of carbamazepine was studied in six normal humans after single and repeated oral doses. The plasma concentrations following single dose (100, 200, 600 mg) were fitted by a one-compartment open model. Using area as a measure, availability was constant in the dose range studied. The elimination half-life ± SEafter a single dose was 37.7±5.7hr; it decreased during chronic treatment to a calculated value around 21 hr. The steady-state plasma concentration, lower than expected from the single-dose study, was adequately predicted from the single-dose data when a correction was made for the increased elimination rate constant. The present findings contrast with the apparently unpredictable plasma levels reported during carbamazepine therapy.
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  • 79
    ISSN: 1573-8744
    Keywords: aspirin ; dissolution ; bioavailability ; effect of antacids ; acid ; capacity ; consuming ; in vivo ; buffering effect
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The in vitrodissolution profile, in vitroand in vivobuffering characteristics, and single-dose bioavailability of various buffered aspirin tablet formulations were studied. Buffering agents,such as magnesium and aluminum hydroxides (formulations B and C) or magnesium carbonate and aluminum glycinate (formulation D), significantly increased the rate of aspirin dissolution from solid dosage forms as compared to an unbuffered tablet (formulation A). The extent of aspirin absorption was equivalent with all formulations;however, the faster rate of dissolution (t50 and t90)with buffered formulations resulted in earlier and higher peak concentration of salicylate compared to that with unbuffered formulation, following a two-tablet dose in the fasting state. A comparison of the in vivobuffer capacity of a four-tablet dose of formulations B and D was performed in the postcibal state at the time of maximal meal-induced acid secretion, using a radiotelemetry procedure for determination of pH. Formulation B prolonged the interval of elevation of intragastric pH 〉 3 for 32 min as compared to 12 min for D.
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  • 80
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    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 133-146 
    ISSN: 1573-8744
    Keywords: bioavailability ; phenytoin sodium capsules ; plasma levels ; human studies
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Eleven single lots of 100-mg phenytoin sodium capsules were evaluated for their relative bioavailability in 12 normal human volunteers. These products were manufactured by eight different companies and met all compendial specifications. The products were evaluated with respect to plasma levels at various times up to 96 hr following administration of single 100-mg doses, times of peak level, peak plasma concentrations, and areas under the plasma level—time curve. Several of the products exhibited statistically significant differences in the various parameters studied.
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  • 81
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    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 183-192 
    ISSN: 1573-8744
    Keywords: propranolol ; kinetics ; volunteers ; bioavailability ; threshold dose
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of propranolol in blood was studied in healthy volunteers, following intravenous administration of 0.1 mg/kg and increasing oral doses of 10,20, and 40 mg, using a specific and sensitive gas Chromatographie method. The systemic availability of orally administered propranolol varied from 9% to 38% between subjects, but it was constant within each subject. A linear relationship was found between the area under the blood concentration-time curve and the oral dose. At variance with literature data, we could not observe a threshold dose.
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  • 82
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    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 99-110 
    ISSN: 1573-8744
    Keywords: bioavailability ; tetracycline HCl capsules ; dose dependency ; brand dependency ; water ingestion ; urinary excretion
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Seven healthy male volunteers were administered, on different occasions, one, two, and three capsules of two commercially available brands (A and B) each containing 250 mg tetracycline HCl. Urinary excretion rates and cumulative amounts of drug excreted in the urine in 4 days were used to assess the bioavailability of the two brands at the different doses studied. The rate constants of absorption and elimination of tetracyline were similar at all dose levels. However, the extent of absorption (F)appears to be dependent on the brand, dose, and volume of water ingested with the drug. Fof Brand B was not significantly different than that of brand A at the 250-mg dose but was decreased by 23.3% (p〈0.01)at the 500-mg dose and by 19.7% (p 〈0.05) at the 750-mg dose. With respect to dose, Fof each brand at the 500-mg dose was not significantly different than its value at the 250-mg dose. However, Fof brand A at the 750-mg dose was reduced by 14.8% (p 〈0.05) and that of brand B by 21.1% (p 〈0.05) relative to their respective values at the single dose. Surprisingly, when the 750-mg dose of brand A was ingested with a small volume of water, Fwas increased by 18.9% (p 〈0.05) compared to the ingestion of the identical dose of the same brand under waterloading conditions.
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  • 83
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    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 547-558 
    ISSN: 1573-8744
    Keywords: statistical moments ; network theory ; pharmacokinetics ; bioavailability ; deconvolution ; plasma concentration-time curve ; urinary excretion rate-time curve ; compartment models
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Statistical moments are parameters that describe the characteristics of the time courses of plasma concentration (area, mean residence time, and variance of residence time) and of the urinary excretion rate that follow administration of a single dose of a drug. The relationship between the moments of a time-course curve and pharmacokinetic profiles of drug disposition, i.e., absorption, distribution, metabolism, and excretion, is described. The moments are related to the extent and rate of bioavailability, and it is shown that they can be effectively applied to the deconvolution operation.
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  • 84
    ISSN: 1573-8744
    Keywords: trapezoidal rule ; area under the curve ; pharmacokinetics ; clearance ; bioavailability ; integration method ; sulfisoxazole
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The linear trapezoidal rule method is commonly used for the estimation of the area under the plasma level-time curve. Error analyses are performed when the method is used in first-order absorption and first-order elimination kinetics in the one-compartment system. It is found that significant underestimations and overestimations in area during the absorption phase and postabsorption phase, respectively, can occur when the method is improperly used. During the exponential postabsorption phase the relative error is only a function of the ratio (n)of the time interval over the half-life of the two plasma data points in the interval. The error from the linear trapezoidal rule method at n=0.5 is about 1%. The error increases to 15.5% and 57.1 % when nis increased to 2 and 4, respectively. It is recommended that for most absorption studies the linear trapezoidal method be used for prepeak and plateau plasma data and the logarithmic trapezoidal method for postpeak plasma data.
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  • 85
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    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 1-27 
    ISSN: 1573-8744
    Keywords: furosemide ; renal failure ; congestive heart failure ; bioavailability ; diuretic effects
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of furosemide and the attempt to correlate biological fluid measurements with diuretic response have been the subject of a large number of studies since the original reports of HajdÚ, Rupp, and coworkers in the mid-1960s. This article attempts to critically review these studies under seven different sections: furosemide pharmacokinetics in normal volunteers, furosemide pharmacokinetics in patients with decreased renal function, furosemide pharmacokinetics in patients with congestive heart failure, furosemide metabolism and assay methods, furosemide bioavailability, dose-response relationships, and the role of inhibitors and mediators on furosemide effects. The literature is reviewed through August 1978.
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  • 86
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    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 295-303 
    ISSN: 1573-8744
    Keywords: tetracycline ; antibiotics ; Billroth-II gastrectomy ; gastrectomy ; pharmacokinetics ; bioavailability
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The bioavailability of a single 250-mg oral dose of tetracycline hydroghloride was studied in seven patients following Billroth-II gastrectomy in comparison with seven control subjects matched for age and body weight. There were no significant differences between control subjects and gastrectomized patients in the apparent lag time prior to the start of absorption (23.6 vs. 22.8 min), peak serum tetracycline concentration (1.72 vs. 1.75 μg/ml), the time of attainment of peak concentrations (3.35 vs. 3.42 hr), the apparent first-order absorption half-life (1.8 vs. 1.4hr), or the apparent first-order elimination half-life (8.0 vs. 8.7hr). Completeness of tetracycline absorption, as judged by area under the 24-hr serum concentration curve, did not differ significantly between the two groups, nor did 24-hr urinary excretion of tetracycline. Thus the abnormalities of gastrointestinal structure and function produced by Billroth -II gastrectomy do not result in impairment of the rate and completeness of tetracycline absorption.
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  • 87
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    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 159-170 
    ISSN: 1573-8744
    Keywords: diphenhydramine ; intravenous infusion ; oral administration ; first-pass effect ; bioavailability
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Plasma levels and urinary excretion of diphenhydramine were measured after administration of three single 50-mg doses of diphenhydramine hydrochloride to two healthy male volunteers as an intravenous infusion, an oral solution, and a commercially available capsule. A large first- pass effect was evident from the data, with about 50% of the drug being metabolized by the liver before it reached the general circulation. The drug in solution given orally appeared to be fully available to the hepatoportal system, and the availability of diphenhydramine from the capsule was about 83% relative to the solution in one subject and 100% in the other subject. Cumulative amounts of unchanged diphenhydramine excreted in the urine were less than 4% of the administered dose. Both subjects went to sleep at the end of the 1-hr intravenous infusion, but were only drowsy following the oral treatments.
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  • 88
    ISSN: 1573-8744
    Keywords: bioavailability ; confidence intervals ; hypothesis testing ; imipramine ; internal standard ; mass spectrometry ; power ; relative bioavailability
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    Topics: Chemistry and Pharmacology
    Notes: Abstract A new methodology for comparative bioavailability testing is described in which each drug formulation is compared with a stable isotope-labeled variant of the drug that is consumed orally in solution at the same time the tested formulation is ingested. The methodology is used to determine the comparative bioavailabilities of two commercially available brands of imipramine hydrochloride. The power of the new methodology to detect differences between drug formulations, when, in fact, such differences exist, is shown to be superior to that of conventional bioavailability tests.
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  • 89
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    Medical & biological engineering & computing 15 (1977), S. 11-17 
    ISSN: 1741-0444
    Keywords: Haemodynamics ; Modelling ; Pulsatile flow
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    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The displacement relationships describing the deformation of an elastic vessel under excess internal pressure which are derived from different theories of elasticity are compared. The main result of the comparison is that theories which take account of the thickness of the wall of the vessel produce a significantly better representation than those theories which treat the wall as a membrane. The classical and statistical theories of thick-walled tubes result in complicated pressure-radius relationships. It is shown that there is little difference between the results of the more exact theories and those for a thin membrane corrected by means of a simple thickness factor. A review of the different theories is necessary to decide which pressure-displacement relationship to apply as an approximation for the elastic properties of arteries. An indication is given of the manner in which the relationship is used in numerical computations. In Part 2 the experimental determination of the pressure-radius relationship for a rubber tube is described. The results are in agreement with the conclusions of the comparison of theoretical treatments in Part 1.
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  • 90
    ISSN: 1741-0444
    Keywords: Haemodialysis ; Modelling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Sommaire On a entrepris un traitement de dialyse sur malade afin d’étudier les phénomènes dynamiques de concentration des déchets (urée et créatinine) et de pression f.s.c. sur un malade rénal au cours du cycle complet des périodes de pré-dialyse, dialyse et post-dialyse. Les concentrations pour les variables du traitement de dialyse sont prédites par le modèle à cinq compartiments de Dedrick et Bischoff, elles comprennent la fréquence et la durée du traitement, la vitesse de formation d’urée chez le malade et la vitesse d’élimination de l’urée par l’appareil de dialyse. Les résultats montrent que la pression f.s.c. baisse au cours de la période de pré-dialyse, augmente rapidement en début de traitement puis se rapproche (sans cependant la dépasser) petit à petit de la valeur normale. L’analyse démontre ainsi qu’une augmentation significative de la pression f.s.c. au cours de l’hémodialyse rapide n’est pas dûe aux changements de concentration de l’urée du cerveau étant mis en valeur par les études de pathophysiologie du syndrome de déséquilibre de dialyse de Arieff et Massry. Si l’augmentation importante et brusque de la pression f.s.c. (immédiatement après le début du traitement) n’est pas désirable, on recommande de commencer la dialyse au point de la vitesse minimale d’élimination de l’urée. Plus tard une hausse lente de la vitesse d’élimination peut s’entreprendre et la fréquence du traitement peut être augmentée afin de limiter la durée des séances d’un traitément.
    Abstract: Zusammenfassung Die Dialysebehandlung von Patienten wurde analysiert, um die Dynamik von metabolischen Abfallstoffkonzentrationen (Harnstoff und Kreatinin) und den CSF-Druck eines Patienten im Laufe des gesamten Zyklus von Vordialyse, Dialyse und der Zeitspanne nach Dialyse zu untersuchen. Die Konzentrationen werden durch das fünfteilige Modell von Dedrick und Bischoff hinsichtlich der Veränderlichen der Dialysebehandlung vorausgesagt, wie Häufigkeit der Benutzung und Behandlungszeit, die Harnstofferzeugungsrate des Patienten und Harnstoff-klärungsrate des Dialysegerätes. Die Ergebnisse deuten an, daß der CSF-Druck in der Zeit vor Dialyse abnimmt, am Anfang der Behandlung stark zunimmt und dann seinen Normalwert allmählich wieder erreicht (aber nicht übersteigt). Die Analyse zeigt daher, daß der signifikante Anstieg des CSF-Drucks bei schneller Hämodialyse nicht durch Änderungen der Harnstoffkonzentrationen im Gehirn verursacht wird, was durch die pathophysiologischen Untersuchungen des Dialyse-Labilität-Syndromsvon, Arieff und Massry bestätigt wird. Wen der große plötzliche Ansteig des CSF-Drucks (unmittelbar nach Anfang der Behandlung) nicht gewünscht wird, wird empfohlen, die Dialyse dann einzuleiten, wenn die niedrigste Harnstoffklärungsrate gegeben ist. Später könnte eine allmähliche Erhöhung der Klärungsrate vorgesehen werden, und die Häufigkeit der Behandlung kann gesteigert werden, um die Dauer einer Behandlung zu kürzen.
    Notes: Abstract A patient-dialysis treatment analysis has been performed, to study the dynamics of metabolic waster concentrations (urea and creatinine) and c.f.s. pressure in a renal patient during the entire cycle of pre-dialysis, dialysis and post-dialysis periods. The concentrations have predicted by the five compartment model of Dedrick and Bischoff, for the dialysis treatment variables, such as frequency of use and treatment time, urea generation rate of the patient and urea clearance rate of the dialyser. The results indicate that the c.f.s. pressure decreases during the pre-dialysis period, increases abruptly at the beginning of the treatment and then approaches (but does not overshoot) its normal value gradually. The analysis thereby shows that the significant rise in c.f.s. pressure in the rapid haemodialysis is not due to changes in the urea concentrations in the brain, which is validated by the pathophysiology studies of dialysis disequilibrium syndrome by Arieff and Massry. If the large abrupt rise in c.f.s. pressure (immediately following the start of treatment) is not desirable, it is recommended that the dialysis be started at the lowest urea clearance rate. Later a gradual increase in the clearance rate may be provided and the treatment frequency can be increased, in order to limit the duration of a treatment session.
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  • 91
    ISSN: 1741-0444
    Keywords: Haemodynamics ; Modelling ; Hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Sommaire Les malades souffrant d'un insuffisance rénale terminale présentent souvent une hypertension liée au mécanisme eau/sodium. Cette étude utilise un modèle mathématique pour établir les relations éventuelles entre les valeurs des volumes d'eau et autres variables hémodynamiques et le comportement du système régulateur de la pression sanguine.
    Abstract: Zusammenfassung Patienten mit Nierenversagen im Endstadium zeigen oft eine wasser/natriumabhängige Hypertension. Diese Studie bedient sich eines mathematischen Modells, um ein etwa bestehendes Verhältnis zwischen den Werten der Wasservolumen und anderer hämodynamischen Veränderlichen und dem Verhalten des Blutdruckregelsystems festzustellen.
    Notes: Abstract Patients with end-stage renal failure often exhibit a water-sodium dependent hypertension. This study employed a mathematical model to establish possible relationships between water volume and other haemodynamic variables and the behaviour of the blood-pressure regulating system.
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  • 92
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    Medical & biological engineering & computing 15 (1977), S. 611-617 
    ISSN: 1741-0444
    Keywords: Haemodynamics ; Modelling ; Pulsatile flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Sommaire Est décrit un modèle mathématique pouvant être utilisé pour calculer la circulation sanguine dans une artère normale à partir de pressions mesurées en deux points différents. Les équations établissant le mouvement d'un fluide dans un tube élastique sont simplifiées mais suffisamment réalistes pour pouvoir être appliquées à la circulation artérielle. On choisit une solution numérique pour les équations dont la moyenne a été établie pour chaque section du tube; ces équations sont résolues par la méthode des différences finies. On choisit un terme de substitution pour la constante de frottement qui ne peut pas être exprimée avec exactitude par ces équations différentielles partielles non linéaires. On démontre combien les résultats sont sensibles aux changements de la constante de frottement. On présente une méthode qui établit le frottement sur les parois grace à une approximation linéaire mais qui, dans le cadre des limites imposées, utilise néanmoins une valeur correcte en amplitude comme en phase. Les effects longeur-entrée sont corrigés. Les propriétés des parois sont représentées par un rapport pression/rayon élaboré à partir d'un précédent ouvrage écrit par les auteurs (Taylor etGerrard, 1976). L'utilisation du modèle est illustrée par l'emploi de données expérimentales citées parStreeter et al. (1963). La solution est parfaitement conforme aux résultats expérimentaux.
    Abstract: Zusammenfassung Ein amthematisches Modell wird beschrieben, mit dessen Hilfe man den Blutdurchflug in einer normalen Arterie aus dem an zwei verschiedenen Punkten gemessenen Druck berechnen kann. Die Gleichungen der Flüssigkeitsbewegung in einem elastischen Schlausch sind zwar vereinfacht, aber ausreichend der Wirklichkeit entsprechend, um auf die Arterien angewendet werden zu können. Man entscheidet für eine numerische Lösung der Gleichungen im Durchschnitt der Schlauchabschnitte, und die Gleichungen werden durch die Methode der endlichen Differenzen gelöst. Der Reibungsausdruck, der in diesen nicht-linearen partiellen Differenzial-gleichungen nicht genau bestimmt werden kann, wird substituiert. Die Sensitivität der Ergebnisse gegenüber Änderungen des Reibungsausdruckes wird aufgezeigt. Eine Methode wird vorgeführt, die die Hautreibung auf einem Linearnäherungswert begründet; innerhalb dieser Grenzen verwendet sie, was Größe Phase betrifft, einenrichtigen Wert. Für Eintrittslängeneffekte wird eine Eerichtigung vorgenommen. Die Eigenschaften der Arterienwand werden durch ein Druck/Radiusverhältnis dargestellt, das in früheren Artikeln von den Verfassern entwickelt wurde (Taylor undGerrard 1976). Die Verwen, dung dieses Modells wird anhand von Versuchsdaten, die vonStreeter u.a. (1963) angeführt wurden, dargelegt. Die Losung laßt sich vorteilhaft mit Versuchsergebnissen vergleichen.
    Notes: Abstract A mathematical model is described which can be used to calculate blood flow in a normal artery from pressures measured at two separated points. The equations of motion of fluid in an elastic tube are simplified but sufficient realism is retained for the application to arterial flow. A numerical solution to the equations averaged over each section of the tube is chosen and these equations are solved by the method of finite differences. A substitution is made for the frictional term which cannot be expressed exactly in these nonlinear partial differential equations. The sensitivity of the results to changes in the friction term is demonstrated. A method is presented which bases the skin friction on a linear approximation, but within this limitation uses a value which is correct in magnitude and phase. A correction is made for entrace-length effects. The wall properties are represented by a pressure-radius relationship developed from previous work by the authors (Taylor and Gerrard, 1976). The use of the model is illustrated by using experimental data quoted by Streeteret al. (1963). The solution compares favourably with the experimental results.
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  • 93
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    Medical & biological engineering & computing 16 (1978), S. 90-97 
    ISSN: 1741-0444
    Keywords: Modelling ; Physiological cardiac pacemaker ; Pulse-frequency modulator
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Sommaire Une correspondance biologique fondée sur un modulateur nous permet d’utiliser les techniques mises au point dans la théorie des communications pour estimer avec quelle justesse le système transmet l’information et réciproquement avec quelle justesse on peut évaluer le signal de contrôle à partir des signes sortants. Des études précédentes ont tiré parti des similitudes existant entre l’activité du système nerveux et un programme de modulation du pouls connus sous le nom de modulation intégrale de la fréquence du pouls (m.i.f.p.). Récemment (Hyndman and Mohn, 1975), le m.i.f.p. a été amélioré par l’adjonction d’une période de repos visant à imiter le stimulateur cardiaque. Dans l’étude actuelle, le m.i.f.p. a été adapté une fois encore pour inclure la variation observée dans le seuil du stimulateur, le potentiel de membrane et la période refractaire, et pour inclure également une évaluation convenable des effets dûs à l’interface stimulateur/système nerveux. Nous avons étudié aussi la manière dont ces sources de variabilité influent sur l’activité du système simulé. L’étude conclut que le filtrage passe-bas de l’information intermittente R-R permettra d’estimer correctement le signal de contrôle nerveux et que le modèle de modulation de la fréquence du pouls est un procédé applicable au système cardiaque et aux autres systèmes physiologiques.
    Abstract: Zusammenfassung Ein auf einem Modulator beruhendes biologisches Analogsystem ermöglicht die Anwendung der in der Kommunikationstheorie verwendeten Technik, um zu schätzen, wie gut das System Information überträgt und wie gut man von der Ausgabe auf das Kontrollsignal schließen kann. Frühere Arbeiten erschöpften die Übereinstimmung von Nervenaktivität und einem Pulsmodulationsschema, das unter der Bezeichnung integrale Pulsfrequenzmoduation (i.p.f.m.) bekannt ist. Vor kurzem (Hyndman und Mohn, 1975) wurde i.p.f.m. durch die Beigabe einer Ruheperiode zum Modell für den Herzschrittmacher entwickelt. Dieser Artikel beschreibt eine weitere Entwicklung, die auch die Schwankungen, die in der Schrittmacherschwelle beobachtet werden, sowie das Membranpotential und die Refraktionsperiode berücksichtigt und die Wirkung der Nerven-Schrittmachergrenzfläche abschätzt. Es wird untersucht, wie diese Schwankungsquellen die Leistung des Simuliersystems beeinflußen. Es ergibt sich, daß die Tiefpaßfiltrierung der R-R-Intervalldaten eine gute Schätzung des Nervkontrollsignals ermöglicht und daß sich das Pulsfrequenzmodulationsmodell auf dieses und andere physiologische Systeme anwenden läßt.
    Notes: Abstract A biological analogue based on a modulator allows one to use the techniques developed in communication theory to estimate how well the system transmits information and, conversely, how well one can estimate the controlling signal from the output. In previous works, the similarities between neural activity and a pulse-modulation scheme known as integral pulsefrequency modulation (i.p.f.m.) were exploited. Recently (Hyndman and Mohn, 1975) i.p.f.m. was adapted by the addition of a dormant period to model the cardiac pacemaker. In the present study, i.p.f.m. is further adapted to include the variability observed in the pacemaker threshold, membrane potential and refractory period, and also to include a reasonable estimate of the effects of the neural-pacemaker interface. How these sources of variability affect the performance of the simulated system is examined. It is concluded that the low-pass filtering of R-R interval data will yield fair estimates of the controlling neural signal and that the pulse frequency-modulation model is applicable to this and other physiological systems.
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  • 94
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    Medical & biological engineering & computing 17 (1979), S. 223-229 
    ISSN: 1741-0444
    Keywords: Metabolic systems ; Modelling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract A case study illustrates the application of systems theory to the analysis of data from nonrepeatable experiments with relatively few data points. The specific problem considered is the compartmental modelling in the human of the metabolic pathways of orally-administered methionine using tolerance test data. Attention is restricted to linear models, and concentrates on the determination of parsimonious structures (i.e. with as few parameters as possible) and their physiological interpretation.
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  • 95
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    Medical & biological engineering & computing 15 (1977), S. 564-572 
    ISSN: 1741-0444
    Keywords: Eye ; Modelling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Sommaire Un modèle mathématique a été réalisé pour déterminer automatiquement l'emplacement d'un type de ruptures rétiniennes détachées. Il s'agit d'un oeil schématique complet tenant compte du rayon et du centre de courbure ainsi que de l'indice de réfraction. Le contrôle par ordinateur permet au chirurgien de corriger le site apparent lors du placement d'un implant dans une opération d' agrafage sur la schlérotique. La longueur de l'acc de retombée sur la chroïde, mesurée sur la surface postérieure de la schlérotique en commençant à partir du prolongement de l'axe de vision jusqu'à la rupture rétinienne, et la somme de deux déplacements: un uniquement dû à la géométrie, l'autre à la relaxation de la rétine. Le déplacement géométrique est l'élément essentiel, car la distance maximale de la partie détachée est considérée comme faible comparée à la distance radiale depuis le centre du globe oculaire. La traction de l'humeur vitrée affectant la relaxation rétinienne est remplacée par une traction globale correspondant à une distance chordale observée entre des points extrêmes et la distance du détachement. La rétine est supposée élastiquement homogène et isotrope et est soumise à une traction normale uniforme de sa surface vers l'intérieur. Les déplacements sont prédits à l'aide d'une théorie non linéaire pout les forts déplacements de membrane. Les résultats d'ordinateur représentatif sont donnés pour le méridien vertical.
    Abstract: Zusammenfassung Es wurde ein mathematisches Modell zur automatischen Lokalisierung einer Klasse abgelöster Netzhautrisse konstruiert. Es schließt ein komplettes schematisches Auge mit Krümmungshalbmesser, Krümmungsmittelpunkt und Brechungsindex ein. Die Computer-Steuerung liefert dem Chirurgen Korrekturen von dem augenscheinlichen Sitz für die Anbringung eines Transplantats in einem skleralen Knickverfahren. Die Bogenlänge der Wiederabsetzung auf die Gefäßhaut, gemessen auf der hinteren Fläche der Sklera und beginning von der Verlängerung der Sichtlinie zum Netzhautriß, ist die Summe von zwei Verlagerungen: eine ausschließlich infolge der Geometrie, die andere infolge der Netzhauterholung. Der geometrische Beitrag ist am wichtigsten, weil der Maximalabstant der Ablösung in Vergleich mit dem Radialabstand von der Mitte des Augapfels als gering angenommen wird. Ein hyalines Ziehen, das die Netzhauterholung beeinträchtigt, wird durch eine geschätzte Gesamtstreckung ersetzt, wodurch ein beobachteter chordaler Abstant zwischen Extremalpunkten und Abstand der Ablösung befriedigt wird. Die Netzhaut wird als elastisch homogen und isotrop und einer gleichförmigen, normalen Oberflächenziehung nach innen ausgesetzt angenommen. Verlagerungen werden mittels einer nichtlinearen Theorie für große Verlagerungen von Membranen vorhergesagt. Für den vertikalen Meridian werden repräsentative Computer-Ergebnisse vermittelt.
    Notes: Abstract A mathematical model has been constructed for determining automatically the localisation of a class of detached retinal breaks. It includes a complete schematic eye in terms of the radius of curvature, centre of curvature and index of refraction. Computer control provides the surgeon with corrections from the apparent site for placement of an implant in a scleral buckling procedure. The arc length of settling back onto the choroid, measured on the posterior surface of the sclera and starting from the extension of the line of sight to the retinal tear, is the sum of two displacements, one solely due to geometry, the other to retinal relaxation. The geometric contribution is paramount because the maximum distance of detachment is taken to be small compared with the radial distance from the centre of the globe. Vitreous traction affecting retinal relaxation is replaced by an estimated overall stretch, satisfying an observed chordal distance between extremal points and distance of the detachment. The retina is assumed elastically homogeneous and isotropic and subject to a uniform normal surface traction directed inward. Displacements are predicted by means of a nonlinear theory for large displacements of membranes. Representative computer results are given for the vertical meridian.
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  • 96
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    Medical & biological engineering & computing 17 (1979), S. 199-206 
    ISSN: 1741-0444
    Keywords: Modelling ; Analogue computer ; Kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract This report describes a model of the renal perfusion dynamic changes that occur during kidney preservation. The model utilises data from physiological experiments performed in this laboratory as well as from observations reported in the literature. Included in the model are the effects of cellular volume changes due to metabolic variations, vascular distensibility and a hypothesised tissue pressure effect observed under some conditions.
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  • 97
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    Medical & biological engineering & computing 16 (1978), S. 471-482 
    ISSN: 1741-0444
    Keywords: Biomechanics ; Modelling ; Urinary bladder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Sommaire Cet article présente un modèle décrivant les propriétés passives de la vessie durant cette phase de collecte. Une technique genre “boîte noire” est utilisée. Le système étudié, qui est défini en terme d'une relation pression/volume, est divisé en quatre sous-systèmes out blocs à savoir deux blocs géométriques, un bloc décrivant les propriétés des parois de la vessie en fonction du temps et un bloc décrivant les propriétés en fonction de sa longueur. Les modèles ont été mis au point et testés pour chaque bloc séparément. En ce qui concerne la géométrie, la vessie est décrite comme une sphère à parois épaisses dont les tissus ont un volume constant. La dépendance des propriétés de ces parois en fonction du temps peut être expliquée avec un modèle visco-élastique, tandis qu'on peut montrer que la relation entre les propriétés de ces parois et leur longueur correspond à des modules élastiques qui dépendent des tensions de manière biexponentielle. Les valeurs estimées des paramètres en question ont été obtenues à la suite d'expériences réalisées sur des bandes de vessies obtenues auprès de l'abattoir local. La combinaison des blocs a donné un modèle global des propriétés passives de la vessie dans la phase de collecte. Ce modèle contient quatorze paramètres. La manière classique d'étudier la vessie, qui consiste à la remplir lentement et à mesurer la pression obtenue, donne une relation pression/volume pseudo-statique appelée un cystométrogramme. Le modèle prédit précisément la forme du cystométrogramme. Cependant, l'analyse d'un tel cystométrogramme classique ne nous permet de déterminer que trois paramètres de notre modèle. Une meilleure méthode de mesure consiste à mettre sous tension de manière graduelle (ou presque) la vessie. Cela permet d'obtenir huit paramètres, pourvu que le volume initial de la vessie soit connu, et plusieurs mesures sur une vessie à différentes tensions nous permettent de déterminer dix paramètres. Les résultats obtenus avec cette méthode de mise sous tension par étape sont compatibles avec le modèle.
    Abstract: Zusammenfassung In diesem Artikel wird ein Modell dargestellt, das die passiven Eigenschaften der Harnblase in der Sammelphase beschreibt. Es wird eine Blackbox-Methode angewandt. Das zu untersuchende System, das als ein Druckvolumenverhältnis definiert wird, wird in vier Teilsysteme oder Spalten aufgeteilt, d.h., zwei Geometriespalten, eine Spalte, die die zeitabhängigen Eigenschaften der Blasenwand darstellt, und eine Spalte, in der die längenabhängigen Eigenschaften beschrieben werden. Für jede Spalte wurden getrennte Modelle konstruiert und getestet. In bezug auf die Geometrie wird die Blase als dickwandige Sphäre mit konstantem Gewebevolumen beschrieben. Die Zeitabhängigkeit der Wandeigenschaften kann anhand eines visko-elastischen Modells erklärt werden. Die Längenabhängigkeit der Wandeigenschaften erweist sich als Erzeuger elastischer Moduli, die bi-exponentiell von der Belastung abhängig sind. Schätzungen der zugehörigen Parameterwerte erhielt man aus Experimenten nit Streifen der Harnblase, die man vom örtlichen Schlachthof bezogen hatte. Die Kombination der Spalten ergab ein Gesantmodell der passiven Eigenschaften der Harnblase in der Sammelphase. Durch die klassische Untersuchungsmethode der Harnblase, sie langsam zu füllen und den hierdurch erzeugten Druck zu messen, erhält man ein pseudo-statisches Druckvolumenverhältnis, Zystometrogramm genannt. Das Modell ergibt eine genaue Voraussage des Zystometrogramms. Jedoch kann man durch die Analyse des klassischen Zystometrogramms nur drei Parameter unseres Modells bestimmen. Ein besseres Meßverfahren beruht auf der stufenweisen (oder fast stufenweisen) Belastung der Harnblase. Eine stufenweise Belastung ergibt acht Parameter vorausgesetzt, daß das Anfangsvolumen der Blase bekannt ist. Mehrere Messungen an einer Blase bei verschiedenen Belastungen ermöglichen es uns, zehn Parameter zu bestimmen. Die Resultate der stufenweisen Belastung sind mit dem Modell vergleichbar.
    Notes: Abstract A model is presented that describes the passive properties of the urinary bladder in the collection phase. A black-box approach is used. The system under investigation, which is defined in terms of a pressure-volume relationship, is divided into four subsystems or blocks, namely two geometry blocks, a block describing the time-dependent properties of the bladder wall, and a block describing its length-dependent properties. Models have been developed and tested for each block separately. With regard to geometry, the bladder is described as a thick-walled sphere of constant tissue volume. The time-dependence of the properties of the wall can be explained using a visco-elastic model, and the length dependence of the wall properties is shown to yield elastic moduli which depend biexponentially on strain. Estimates of the value of the parameters involved were obtained from experiments on strips of urinary bladder, obtained from the local slaughterhouse. Combination of the blocks yielded an overall model of the passive properties of the urinary bladder in the collection phase. The model contains 14 parameters. The classical way of investigating the urinary bladder, by filling it slowly and measuring the pressure produced, yields a pseudostatic pressure-volume relationship called a cystometrogram. The model predicts the form of the cystometrogram accurately. However, analysis of a classical cystometrogram enables us to determine only three parameters of our model. A better measurement method is based on stepwise (or almost stepwise) straining of the urinary bladder. One stepwise straining yields eight parameters, provided the initial volume of the bladder is known, and several measurements on one bladder at different strains enable us to determine ten parameters. The results obtained with stepwise straining are compatible with the model.
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    Medical & biological engineering & computing 17 (1979), S. 216-222 
    ISSN: 1741-0444
    Keywords: Metabolic systems ; Modelling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The adequacy of present-day measurement techniques for the compartmental modelling of metabolic systems is investigated using numerical examples and analysis of experimentally-obtained plasma clearance curves. It is concluded that the model parameters obtained are often of questionable accuracy. The situation can be improved by careful monitoring of experimental conditions and judicious spacing of data points on the response curve, but the work shows a clear need for a continuous (or semicontinuous) method of monitoring plasma concentration. To resolve ambiguities between models equally plausible on physiological grounds, it is necessary to monitor the dynamics of internal variables, for example, of the concentration in the liver (which is nowadays possible noninvasively).
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