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  • 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects
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  • 1
    Publication Date: 2021-06-14
    Description: Methane plays an important role in the Earth’s atmospheric chemistry and radiative balance being the most important greenhouse gas after carbon dioxide. It has recently been established that geogenic gases contribute significantly to the natural CH4 flux to the atmosphere (Etiope et al., 2008). Volcanic/geothermal areas contribute to this flux, being the site of widespread diffuse degassing of endogenous gases (Chiodini et al., 2005). In such an environment soils are a source rather than a sink for atmospheric CH4 (Cardellini et al., 2003; Castaldi and Tedesco, 2005; D’Alessandro et al., 2009; 2011; 2013). Due to the fact that methane soil flux measurements are laboratory intensive, very few data have been collected until now in these areas. Preliminary studies (Etiope et al., 2007) estimated a total CH4 emission from European geothermal and volcanic systems in the range 4-16 kt a-1. This estimate was obtained indirectly from CO2 or H2O output data and from CO2/CH4 or H2O/CH4 values measured in the main gaseous manifestations. Such methods, although acceptable to obtain order-of-magnitude estimates, completely disregard possible methanotrophic activity within the soil. At the global scale, microbial oxidation in soils contributes for about 3-9% to the total removal of methane from the atmosphere. But the importance of methanotrophic organisms is even larger because they oxidise the greatest part of the methane produced in the soil and in the subsoil before its emission to the atmosphere. Environmental conditions in the soils of volcanic/geothermal areas (i.e. low oxygen content, high temperature and proton activity, etc.) have been considered inadequate for methanotrophic microrganisms. But recently, it has been demonstrated that methanotrophic consumption in soils occurs also under such harsh conditions due to the presence of acidophilic and thermophilic Verrucomicrobia. These organisms were found in Italy at the Solfatara di Pozzuoli (Pol et al., 2007), in New Zealand at Hell’s Gate (Dunfield et al., 2007) and in Kamchatka, Russia (Islam et al., 2008). Both the Italian and the Hellenic territories are geodynamically very active with many active volcanic and geothermal areas. Here we report on methane flux measurements made at Pantelleria (Italy) and at Sousaki and Nisyros (Greece). The total methane output of these three systems is about 10, 19 and 1 t a-1, respectively (D’Alessandro et al., 2009; 2011; 2013). The total emissions obtained from methane flux measurements are up to one order of magnitude lower than those obtained through indirect estimations. Clues of methanotrophic activity within the soils of these areas can be found in the CH4/CO2 ratio of the flux measurements which is always lower than that of the respective fumarolic manifestations, indicating a loss of CH4 during the travel of the gases towards earth’s surface. Furthermore laboratory methane consumption experiments made on soils collected at Pantelleria and Sousaki revealed, for most samples, CH4 consumption rates up to 9.50 µg h-1 and 0.52 µg h-1 respectively for each gram of soil (dry weight). Only few soil samples displayed no methane consumption activity. Finally, microbiological and molecular investigations allowed us to identify the presence of methanotrophic bacteria belonging to the Verrucomicrobia and to the Alpha- and Gamma-Proteobacteria in the soils of the geothermal area of Favara Grande at Pantelleria. While the presence of the former was not unexpected due to the fact that they include acidophilic and thermophilic organisms that were previously found in other geothermal environments, the latter are generally considered not adapted to live in harsh geothermal environments. Their presence in the soils of Pantelleria could be explained by the fact that these soils do not have extremely low pH values (〉5). Indeed thermotollerant methanotrophic Gamma-proteobacteria, have been previously found in the sediments of thermal springs in Kamchatka (Kizilova et al., 2012). Such species could find their niches in the shallowest part of the soils of Favara Grande were the temperatures are not so high and they thrive on the abundant upraising hydrothermal methane.
    Description: Published
    Description: Patras, Greece
    Description: 4.5. Studi sul degassamento naturale e sui gas petroliferi
    Description: open
    Keywords: soil methane fluxes ; methanotrophic activity ; geothermal areas ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Oral presentation
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  • 2
    Publication Date: 2017-04-04
    Description: Methane plays an important role in the Earth’s atmospheric chemistry and radiative balance being the second most important greenhouse gas after carbon dioxide. Methane is released to the atmosphere by a wide number of sources, both natural and anthropogenic, with the latter being twice as large as the former (IPCC, 2007). It has recently been established that significant amounts of geological methane, produced within the Earth’s crust, are currently released naturally into the atmosphere (Etiope, 2004). Active or recent volcanic/geothermal areas represent one of these sources of geological methane. But due to the fact that methane flux measurements are laboratory intensive, very few data have been collected until now and the contribution of this source has been generally indirectly estimated (Etiope et al., 2007). The Greek territory is geodynamically very active and has many volcanic and geothermal areas. Here we report on methane flux measurements made at two volcanic/geothermal systems along the South Aegean volcanic arc: Sousaki and Nisyros. The former is an extinct volcanic area of Plio-Pleistocene age hosting nowadays a low enthalpy geothermal field. The latter is a currently quiescent active volcanic system with strong fumarolic activity due to the presence of a high enthalpy geothermal system. Both systems have gas manifestations that emit significant amounts of hydrothermal methane and display important diffuse carbon dioxide emissions from the soils. New data on methane isotopic composition and higher hydrocarbon contents point to an abiogenic origin of the hydrothermal methane in the studied systems. Measured methane flux values range from –48 to 29,000 (38 sites) and from –20 to 1100 mg/mˆ2/d (35 sites) at Sousaki and Nisyros respectively. At Sousaki measurement sites covered almost all the degassing area and the diffuse methane output can be estimated in about 20 t/a from a surface of about 10,000 mˆ2. At Nisyros measurements covered the Stephanos and Kaminakia areas, which represent only a part of the entire degassing area. The two areas show very different methane degassing pattern with latter showing much higher flux values. Methane output can be estimated in about 0.25 t/a from an area of about 30,000 mˆ2 at Stephanos and about 1 t/a from an area of about 20,000 mˆ2 at Kaminakia. The total output from the entire geothermal system of Nisyros probably should not exceed 2 t/a.
    Description: Published
    Description: Vienna, Austria
    Description: 4.5. Studi sul degassamento naturale e sui gas petroliferi
    Description: open
    Keywords: methane output ; diffuse degassing ; volcanic/hydrothermal systems ; Greece ; 01. Atmosphere::01.01. Atmosphere::01.01.03. Pollution ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 05. General::05.02. Data dissemination::05.02.01. Geochemical data ; 05. General::05.08. Risk::05.08.01. Environmental risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Poster session
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  • 3
    Publication Date: 2017-04-04
    Description: A biomonitoring survey, above tree line level, using two endemic species (Senecio aethnensis and Rumex aethnensis) was performed on Mt. Etna, in order to evaluate the dispersion and the impact of volcanic atmospheric emissions. Samples of leaves were collected in summer 2008 from 30 sites in the upper part of the volcano (1500- 3000 m a.s.l). Acid digestion of samples was carried out with a microwave oven, and 44 elements were analyzed by using plasma spectrometry (ICP-MS and ICP-OES). The highest concentrations of all investigated elements were found in the samples collected closest to the degassing craters, and in the downwind sector, confirming that the eastern flank of Mt. Etna is the most impacted by volcanic emissions. Leaves collected along two radial transects from the active vents on the eastern flank, highlight that the levels of metals decrease one or two orders of magnitude with increasing distance from the source. This variability is higher for volatile elements (As, Bi, Cd, Cs, Pb, Sb, Tl) than for more refractory elements (Al, Ba, Sc, Si, Sr, Th, U). The two different species of plants do not show significant differences in the bioaccumulation of most of the analyzed elements, except for lanthanides, which are systematically enriched in Rumex leaves. The high concentrations of many toxic elements in the leaves allow us to consider these plants as highly tolerant species to the volcanic emissions, and suitable for biomonitoring researches in the Mt. Etna area.
    Description: Published
    Description: Vienna, Austria
    Description: 4.4. Scenari e mitigazione del rischio ambientale
    Description: open
    Keywords: Mt. Etna ; biomonitoring ; Trace elements ; 01. Atmosphere::01.01. Atmosphere::01.01.03. Pollution ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 05. General::05.02. Data dissemination::05.02.01. Geochemical data ; 05. General::05.08. Risk::05.08.01. Environmental risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Poster session
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  • 4
    Publication Date: 2017-04-04
    Description: This guide reports the description of the experimental apparata in use in the experimental petrology along with an accurate description of some applications of these instrumentations. After a brief introduction concerning what is the experimental petrology and what is used for, we provide a description of the starting materials used in this field of the Earth Sciences. Moreover, particular attention is focused on these apparata used all around the world. We, finally, introduce some examples of different studies conducted with the different experimental equipments. The aim of this guide is, then, to give information concerning the equipments and their potentiality.
    Description: Published
    Description: 1-20
    Description: 2.3. TTC - Laboratori di chimica e fisica delle rocce
    Description: N/A or not JCR
    Description: open
    Keywords: Piston cylinder ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 5
    Publication Date: 2017-04-04
    Description: Volcanoes represent an important natural source of several trace elements to the atmosphere. For some species (e.g., As, Cd, Pb and Se) they may be the main natural source and thereby strongly influencing geochemical cycles from the local to the global scale. Mount Etna is one of the most actively degassing volcanoes in the world, and it is considered to be, on the long-term average, the major atmospheric point source of many environmental harmful compounds. Their emission occurs either through continuous passive degassing from open-conduit activity or through sporadic paroxysmal eruptive activity, in the form of gases, aerosols or particulate. To estimate the environmental impact of magma-derived trace metals and their depositions processes, rainwater and snow samples were collected at Mount Etna area. Five bulk collectors have been deployed at various altitudes on the upper flanks around the summit craters of the volcano; samples were collected every two week for a period of one year and analyzed for the main chemical-physical parameters (electric conductivity and pH) and for major and trace elements concentrations. Chemical analysis of rainwater clearly shows that the volcanic contribution is always prevailing in the sampling site closest to the summit crater (about 1.5 km). In the distal sites (5.5-10 km from the summit) and downwind of the summit craters, the volcanic contribution is also detectable but often overwhelmed by anthropogenic or other natural (seawater spray, geogenic dust) contributions. Volcanic contribution may derive from both dry and wet deposition of gases and aerosols from the volcanic plume, but sometimes also from leaching of freshly emitted volcanic ashes. In fact, in our background site (7.5 km in the upwind direction) volcanic contribution has been detected only following an ash deposition event. About 30 samples of fresh snow were collected in the upper part of the volcano, during the winters 2006 and 2007 to estimate deposition processes at high altitude during cold periods. Some of the samples were collected immediately after a major explosive event from the summit craters to understand the interaction between snow and fresh erupted ash. Sulphur, Chlorine and Fluorine, are the major elements that prevailingly characterize the volcanic contribution in atmospheric precipitation on Mount Etna, but high concentrations of many trace elements are also detected in the studied samples. In particular, bulk deposition samples display high concentration of Al, Fe, Ti, Cu, As, Rb, Pb, Tl, Cd, Cr, U and Ag, in the site most exposed to the volcanic emissions: median concentration values are about two orders of magnitude higher than those measured in our background site. Also in the snow samples the volcanic signature is clearly detectable and decreases with distance from the summit craters. Some of the analysed elements display very high enrichment values with respect to the average crust and, in the closest site to the summit craters, also deposition values higher than those measured in polluted urban or industrial sites.
    Description: Published
    Description: Vienna, Austria
    Description: 4.5. Degassamento naturale
    Description: open
    Keywords: Mt. Etna ; trace elements ; rainwater ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 03. Hydrosphere::03.03. Physical::03.03.01. Air/water/earth interactions ; 03. Hydrosphere::03.04. Chemical and biological::03.04.03. Chemistry of waters
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Oral presentation
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  • 6
    Publication Date: 2017-04-04
    Description: Improving the constraints on the atmospheric fate and depletion rates of acidic compounds persistently emitted by non-erupting (quiescent) volcanoes is important for quantitatively predicting the environmental impact of volcanic gas plumes. Here, we present new experimental data coupled with modelling studies to investigate the chemical processing of acidic volcanogenic species during tropospheric dispersion. Diffusive tube samplers were deployed at Mount Etna, a very active open-conduit basaltic volcano in eastern Sicily, and Vulcano Island, a closed-conduit quiescent volcano in the Aeolian Islands (northern Sicily). Sulphur dioxide (SO2), hydrogen sulphide (H2S), hydrogen chloride (HCl) and hydrogen fluoride (HF) concentrations in the volcanic plumes (typically several minutes to a few hours old) were repeatedly determined at distances from the summit vents ranging from 0.1 to ~10 km, and under different environmental conditions. At both volcanoes, acidic gas concentrations were found to decrease exponentially with distance from the summit vents (e.g., SO2 decreases from ~10,000 μg/m3 at 0.1 km from Etna’s vents down to ~7 _μg/m3 at ~10km distance), reflecting the atmospheric dilution of the plume within the acid gas-free background troposphere. Conversely, SO2/HCl, SO2/HF, and SO2/H2S ratios in the plume showed no systematic changes with plume aging, and fit source compositions within analytical error. Assuming that SO2 losses by reaction are small during short-range atmospheric transport within quiescent (ash-free) volcanic plumes, our observations suggest that, for these short transport distances, atmospheric reactions for H2S and halogens are also negligible. The one-dimensional model MISTRA was used to simulate quantitatively the evolution of halogen and sulphur compounds in the plume of Mt. Etna. Model predictions support the hypothesis of minor HCl chemical processing during plume transport, at least in cloud-free conditions. Larger variations in the modelled SO2/HCl ratios were predicted under cloudy conditions, due to heterogeneous chlorine cycling in the aerosol phase. The modelled evolution of the SO2/H2S ratios is found to be substantially dependent on whether or not the interactions of H2S with halogens are included in the model. In the former case, H2S is assumed to be oxidized in the atmosphere mainly by OH, which results in minor chemical loss for H2S during plume aging and produces a fair match between modelled and measured SO2/H2S ratios. In the latter case, fast oxidation of H2S by Cl leads to H2S chemical lifetimes in the early plume of a few seconds, and thus SO2 to H2S ratios that increase sharply during plume transport. This disagreement between modelled and observed plume compositions suggests that more in-detail kinetic investigations are required for a proper evaluation of H2S chemical processing in volcanic plumes.
    Description: Published
    Description: 1441-1450
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: 4.5. Degassamento naturale
    Description: JCR Journal
    Description: open
    Keywords: Mt. Etna ; volcanic gas plumes ; tropospheric processing ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 7
    Publication Date: 2017-04-04
    Description: Volcanic and geothermal areas are one of the major natural sources of H2S to the atmosphere. Its environmental impact is often the main cause of the opposition to the development of geothermal energy exploitation programs. In this paper we analyze the air concentrations and dispersion pattern of naturally emitted H2S at the geothermal area of Sousaki (Corinthia, Greece). Measurements, made with a network of passive samplers, evidence a rapid decrease of concentration values away from the emission points. The fact that the decrease is more pronounced in the summer with respect to the winter indicates that it is not only due to a dilution effect, but also to redox reactions favoured by higher temperatures and intense sunlight typical of the summer period.
    Description: Published
    Description: 1723-1728
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: JCR Journal
    Description: reserved
    Keywords: Hydrogen sulphide ; Environmental impact of volcanic activity ; Gas hazard ; Passive samplers ; 01. Atmosphere::01.01. Atmosphere::01.01.03. Pollution ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 8
    Publication Date: 2017-04-04
    Description: Active volcanoes are thought to be important contributors to the atmospheric mercury (Hg) budget, and this chemical element is one of the most harmful atmospheric pollutants, owing to its high toxicity and long residence time in ecosystems. There is, however, considerable uncertainty over the magnitude of the global volcanic Hg flux, since the existing data on volcanogenic Hg emissions are sparse and often ambiguous. In an attempt to extend the currently limited dataset on volcanogenic Hg emissions, we summarize the results of Hg flux measurements at seven active open-conduit volcanoes; Stromboli, Asama, Miyakejima, Montserrat, Ambrym, Yasur, and Nyiragongo.. Data from the domebuilding Soufriere Hills volcano are also reported. Using our determined mercury to SO2 mass ratios in tandem with the simultaneously-determined SO2 emission rates, we estimate that the 7 volcanoes have Hg emission rates ranging from 0.2 to 18 t yr-1 (corresponding to a total Hg flux of ~41 t·yr-1). Based on our dataset and previous work, we propose that a Hg/SO2 plume ratio ~10-5 is bestrepresentative of gas emissions from quiescent degassing volcanoes. Using this ratio, we infer a global volcanic Hg flux from persistent degassing of ~95 t·yr-1
    Description: Published
    Description: 497-510
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: 2.4. TTC - Laboratori di geochimica dei fluidi
    Description: JCR Journal
    Description: restricted
    Keywords: Volcanogenic mercury ; Mercury ; Volcanic plume ; Mercury flux ; Mercury inventories ; Atmospheric mercury ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 04. Solid Earth::04.02. Exploration geophysics::04.02.01. Geochemical exploration ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 9
    Publication Date: 2017-04-04
    Description: Emissions of volcanoes and their depositions do have an immediate impact on their surrounding environment. In the present study, emissions and depositions of the active volcanic and geothermal system Vulcano (Italy) were investigated by active moss biomonitoring (Fig. 1) in the spring of 2012. Sphagnum moss bags were exposed for periods of 3 days, 3, 6 and 9 weeks. Soil and rainwater samples as well as meteorological data were also collected. After exposure, mosses were oven-dried, grinded and each sample was extracted either in deionized water or HNO3 (with H2O2). Extraction solutions were analyzed by ICP-MS for total concentrations of Li, Mg, Sr, Ba, Cr, Mn, S, Fe, Co, Cu, Zn, Mo, W, Tl, As, Sb, Bi, I, and Se. Soil and rain water samples were analyzed for the same trace elements. For elements such as As and Tl, deionized water extracts showed comparable concentrations to HNO3 extracts, indicating either the absence of particles or the presence of water-soluble particles. Elements such as Pb, Ba, Se and Sr were only dissolved to about 10 % or less in deionized water, indicating a significant share of water-insoluble particle formation. Distribution patterns of emissions and depositions over the whole island of Vulcano allowed classifying all investigated elements into four groups based on their origin (Fig. 2). Lithium was found ubiquitously on the island thus likely is of either marine or geogenic origin (group a in Fig. 2). The elements Mg, Fe, Sr, Mn, Zn, Co, and W were found predominantly on the crater where bare soil was present, and were grouped as “soilborne elements” (group b). These elements are characterized by deposition close to their source of origin. Elements with higher concentrations at the fumarolic field were grouped according to their transport characteristics. The elements I, Se, Tl, Bi, Sb, As, and S were considered as true volatiles (group c) being found also further away from the fumarolic field than Pb, Cr, Mo, and Ba which were interpreted to be predominantly emitted as particles (group d). Moss-bag biomonitoring proved to be an effective tool for the study of emission and deposition processes in active volcanic areas which also allows a classification of elements accumulated on the moss by their origin and distribution patterns.
    Description: Published
    Description: Patras, Greece
    Description: 4.5. Studi sul degassamento naturale e sui gas petroliferi
    Description: open
    Keywords: Moss-bags ; trace elements ; biomonitoring ; volcanic emissions ; 01. Atmosphere::01.01. Atmosphere::01.01.03. Pollution ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Oral presentation
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  • 10
    Publication Date: 2017-04-04
    Description: Here, we report the first continuous data of geochemical parameters acquired directly from the active summit crater of Vulcano. This approach provides a means to better investigate deep geochemical processes associated with the degassing system of Vulcano Island. In particular, we report on soil CO2 fluxes from the upper part of Vulcano, a closed-conduit volcano, from September 2007 to October 2010. Large variations in the soil CO2 and plume SO2 fluxes (order of magnitude), coinciding with other discontinuous geochemical parameters (CO2 concentrations in fumarole gas) and physical parameters (increase of shallow seismic activity and fumarole temperatures) have been recorded. The results from this work suggest new prospects for strengthening geochemical monitoring of volcanic activity and for improving the constraints in the construction of a “geochemical model”, this being a necessary condition to better understand the functioning of volcanic systems.
    Description: Published
    Description: 1859-1863
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: 4V. Vulcani e ambiente
    Description: 5V. Sorveglianza vulcanica ed emergenze
    Description: 1R. Reti di monitoraggio e Osservazioni
    Description: JCR Journal
    Description: restricted
    Keywords: Vulcano Island ; Geochemical monitoring ; CO2 flux ; CO2 fumaroles ; SO2 flux ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk ; 05. General::05.02. Data dissemination::05.02.01. Geochemical data
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 11
    Publication Date: 2017-04-04
    Description: Volcanic emissions are considered one of the major natural sources of several trace metals (e.g. As, Cd, Cu, Pb, and Zn) to the atmosphere [Nriagu, 1989], and the geochemical cycles of these elements have to be considered strongly influenced by volcanic input. However, the accurate estimation of the global volcanic emissions of volatile trace metals into the atmosphere is still affected by a high level of uncertainty. The latter depends on the large variability in the emission of the different volcanoes, and on their changing stage of activity. Moreover, only few of the potential sources in the world have been directly measured [Hinkley et al. 1999]. Atmospheric deposition processes (wet and dry) are the pathways through which volcanic emissions return to the ground (soils, plants, aquifers), resulting in both harmful and beneficial effects [Baxter et al. 1982; Aiuppa et al. 2000; Brusca et al. 2001; Delmelle, 2003; Bellomo et al. 2007; Martin et al. 2009; Floor et al. 2011; Calabrese et al. 2011]. In the first part of this study we present the results of a literature review on trace metals emissions from active volcanoes around the world. In the second part, we present new data on the fluxes of the trace metals from Etna (Italy) and four active volcanoes in the world: Turrialba (Costarica), Nyiragongo (DRC), Mutnovsky and Gorely (Kamchatka). We found 27 publications (the first dating back to the 70’s), 13 of which relate to the Etna and the other include some of the world’s most active volcanoes: Mt. St. Helens, Erebus, Merapi, White Island, Kilauea, Popocatepetl, Galeras, Indonesian arc, Satasuma and Masaya. The review shows that currently there are very few data available, and that the most studied volcano is Mt. Etna. Using these data, we defined a range of fluxes for As, Ba, Bi, Cd, Cu, Fe, Mn, Pb, Se, V and Zn (Figure 1). To obtain new data we sampled particulate filters at the five above mentioned volcanoes. Filters were mineralized (acid digestion) and analyzed by ICP-MS. Sulphur to trace element ratios were related to sulphur fluxes to indirectly estimate trace elements fluxes. Etna confirms to be one of the greatest point sources in the world. The Nyiragongo results to be also a significant source of metals to the atmosphere, especially considering its persistent state of degassing from the lava lake. Also Turrialba and Gorely have high emission rates of trace metals considering the global range. Only Mutnovsky Volcano show values which are sometimes lower than the range obtained from the review, consistent with the fact that it is mainly a fumarolic field. This work highlights the need to expand the current dataset including many other active volcanoes for a better constraint of global trace metal fluxes from active volcanoes.
    Description: Published
    Description: Nicolosi (Catania)
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: open
    Keywords: Volcanic degassing ; trace elements ; environmental impact of volcanic activity ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Oral presentation
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  • 12
    Publication Date: 2017-04-04
    Description: Volcanic emissions represent one of the most relevant natural sources of trace elements to the troposphere, both during and between eruptions. Due to their potential toxicity they may have important environmental impacts from the local to the global scale. Mount Etna, the largest European volcano and one of the most active volcano in the world, covers an area of about 1250 km2 and reaches an altitude of about 3340 m. It has been persistently active during historical time, with frequent paroxysmal episodes separated by passive degassing periods. Atmospheric precipitation was collected approximately every two weeks, from April 2006 to December 2007, using a network of five rain gauges, located at various altitudes on the upper flanks around the summit craters of Etna Volcano. The collected samples were analysed for major (Ca, Mg, K, Na, F, SO4, Cl, NO3) and a large suite of trace elements (Ag, Al, As, Au, B, Ba, Be, Bi, Cd, Co, Cr, Cs, Cu, Fe, Hg, La, Li, Mn, Mo, Ni, Pb, Rb, Si, Sb, Sc, Se, Sr, Th, Ti, Tl, U, V, Zn) by using different techniques (IC, SPEC, ICP-MS and CV-AFS). The monitoring of atmospheric deposition gave the opportunity to occasionally sample volcanic fresh ashes emitted by the volcano during the paroxysmal events. This was possible because the network of five rain gauges were equipped with a filter-system to block the coarse material. In this way, more than twenty events of ashfall were collected. Unfortunately, only half of these samples were suitable for a complete chemical analysis, because of the small amount of sample. In order to obtain elemental chemical composition of ashes, powdered samples were analysed by a combination of methods, including X-ray Fluorescence Spectroscopy (XRF), total digestion followed by Inductively Coupled Plasma Emission Mass Spectrometry (ICP-MS), Instrumental Neutron Activation Analysis (INAA), and infrared detection (IR). The chemistry of rainwater reveals that most of the investigated elements have higher concentrations close to the emission vent of the volcano, confirming the prevailing volcanic contribution. Rainwater composition clearly reflects the volcanic plume input. Ash-normalised rainwater composition indicates a contrasting behaviour between volatile elements, which are highly-enriched in rainwater, and refractory elements, which have low rainwater/ash concentration ratios. The degree of interaction between collected ash and rainwater was variable, depending on several factors: (i) the length of the period in which tephra was present in the sampler (the ash fall may have occurred any day from the first to the last day of the rain collecting period); (ii) the amount of rainwater fallen on the collectors after the ash-fall event, and its acidity; (iii) the granulometry of the ash samples that was widely variable (from few centimetres to micrometric particles) increasing the interaction with decreasing dimensions of the grains; (iv) the distance of collector with respect to the craters. In order to investigate the role of volcanic ash on the evolution of the rainwater chemistry, absolute concentrations of rain and ash were plotted in binary plot diagrams (Figure 1). Each diagram corresponds to a single event, and pH and TDS of the solution collected is reported. The diagonal bars in the diagrams represent the rain/ash ratios (1:1 and 1:10000). The results confirm that sulphate and halide salt aerosols are adsorbed onto ash particles, and their rate of dissolution in rainwater depends on solubility. Moreover, rapid chemical weathering of the silicate glass by volcanic acid (SO2, HCl and HF) can also explain the enrichment of several refractory elements (Na, K, Ca, Mg, Si, Al, Fe, Ti, Sc). Our observations highlight how explosive activity can increase enormously the deposition rate of several chemical elements, up to several km away from the emission vents.
    Description: Published
    Description: Nicolosi (Catania)
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: open
    Keywords: volcanic ash ; trace elements ; environmental impact of volcanic activity ; rainwater chemistry ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 13
    Publication Date: 2019-11-04
    Description: Volcanic eruptions are unsteady multiphase phenomena, which encompass many inter-related processes across the whole range of scales from molecular and microscopic to macroscopic, synoptic and global. We provide an overview of recent advances in numerical modelling of volcanic effects, from conduit and eruption column processes to those on the Earth s climate. Conduit flow models examine ascent dynamics and multiphase processes like fragmentation, chemical reactions and mass transfer below the Earth surface. Other models simulate atmospheric dispersal of the erupted gas-particle mixture, focusing on rapid processes occurring in the jet, the lower convective regions, and pyroclastic density currents. The ascending eruption column and intrusive gravity current generated by it, as well as sedimentation and ash dispersal from those flows in the immediate environment of the volcano are examined with modular and generic models. These apply simplifications to the equations describing the system depending on the specific focus of scrutiny. The atmospheric dispersion of volcanic clouds is simulated by ash tracking models. These are inadequate for the first hours of spreading in many cases but focus on long-range prediction of ash location to prevent hazardous aircraft - ash encounters. The climate impact is investigated with global models. All processes and effects of explosive eruptions cannot be simulated by a single model, due to the complexity and hugely contrasting spatial and temporal scales involved. There is now the opportunity to establish a closer integration between different models and to develop the first comprehensive description of explosive eruptions and of their effects on the ground, in the atmosphere, and on the global climate.
    Description: Published
    Description: JCR Journal
    Description: open
    Keywords: numerical modeling ; explosive volcanic eruptions ; conduit flow ; multiphase flow simulation ; stratospheric sulfate aerosol ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 04. Solid Earth::04.08. Volcanology::04.08.99. General or miscellaneous ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases
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  • 14
    Publication Date: 2017-04-04
    Description: Natural precipitation and water samples from passive devices were collected at Mt. Vesuvius and Vulcano Island, Italy, during the period 2004–2006, in order to investigate its possible interactions with fumarolic gases. Evidence of chemical reactions between fumarolic fluids and rain samples before and after its deposition into the sampling devices was found at Vulcano Island. Very low pH values (down to 2.5) and significant amounts of chlorine and sulfate (up to 22 mEq/l) were measured at sampling points located close to the fumarolic field. In contrast, anthropogenic contributions and/or dissolution of aerosols (both maritime and continental) influence the chemistry of rainwaters at Mt. Vesuvius, which show inter-annual variations that are highly consistent with those recorded at the coastal site at Vulcano Island. Chemistry of waters directly exposed to fumarolic fluids may then give useful information about its temporal evolution, holding the signal of the ‘‘maximum’’ chemical event occurred in the meanwhile. In addition, the observation of the health status of vegetation colonizing the immediate surroundings of the fumarolic fields, due to its strong dependence on the interactions with these fluids, may work as a possible biomarker of volcanic activity.
    Description: Published
    Description: 159-171
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: JCR Journal
    Description: restricted
    Keywords: Precipitation ; Fumarole ; Vesuvius ; Vulcano ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 15
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    Risk analysis 19 (1999), S. 711-726 
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
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  • 16
    ISSN: 1539-6924
    Keywords: MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 μg/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 μg/kg/day based on studies of a fish-eating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled 1000 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 μg/kg/day and an MRL of 0.3 μg/kg/day.
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  • 17
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    European journal of nutrition 24 (1985), S. 113-119 
    ISSN: 1436-6215
    Keywords: Chloramphenicol ; pharmacokinetics ; residue ; pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary Residues of Chloramphenicol (CAP) were examined in 24 pigs after intramuscular injection of 30 mg CAP/kg body weight. Two pigs were slaughtered after 3, 6, 12,18, 24, 36 hours, 2, 3, 6, 10, 21 and 30 days, respectively. CAP-concentrations were determined in muscle, blood, urine, liver, kidney, bile, and fat. Methods used were gas-liquid chromatography and radioimmunoassay. Detection limits reached were 1−5 ppb. The concentration-time curves obtained reflected a long elimination phase and allowed only calculation of this half-life. Elimination half-life was estimated to be for muscle, blood and urine 160–170 hours, for kidney 310 and for bile 250 hours. Significant correlations were found to exist between CAP-concentrations in plasma and muscle. It appears that blood would be a good body fluid for monitoring CAP-residues in tissue.
    Notes: Zusammenfassung Zur Untersuchung des Rückstandsverhaltens von Chloramphenicol (CAP) wurden 24 Mastschweine, 24–28 Wochen alt, intramuskulär mit 30 mg CAP/kg Körpergewicht behandelt und je 2 Tiere nach 3, 6, 12, 18, 24, 36 Stunden, 2, 3, 6, 10, 21 und 30 Tagen geschlachtet. Die CAP-Gehalte in Muskulatur, Blut, Urin, Leber, Niere, Galle und Fett wurden gaschromatographisch und radioimmunologisch bestimmt. Die Nachweisgrenze beider Methoden liegt in Abhängigkeit von der Matrix zwischen 1 und 5 ppb. Die erhaltenen Kinetiken weisen eine terminale Elimination auf, deren Halbwertszeiten für Muskulatur, Blut und Urin ca. 160–170 Stunden, für Niere 310 Stunden und für Galle 250 Stunden betragen. Die CAP-Konzentration in Muskulatur und Blut weisen eine signifikante, lineare Korrelation auf. Blutuntersuchungen könnten deshalb als Screening-Methode bei umfangreichen Rückstandskontrollen eingesetzt werden.
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  • 18
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    European journal of nutrition 22 (1983), S. 14-26 
    ISSN: 1436-6215
    Keywords: branched chain α-keto acids ; 4-methyl-2-oxopentanoate, 3-methyl-2-oxopentanoate ; 3-methyl-2-oxobutyrate ; dehydrogenation ; transamination ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Michaelis-Konstanten und Aktivitäten von Dehydrogenasen und Transaminasen der drei verzweigten α-Ketosäuren Keto-Valin, Keto-Leucin und Keto-Isoleucin in Leber, Niere, Skeletmuskel und Gehirn von Ratten werden mitgeteilt. Nach oraler Zufuhr passieren nur 11–22% der Ketosäuren unverändert die Leber. Aus pharmakokinetischen und Resorptions-Untersuchungen erhaltene Blutspiegel an Ketosäuren werden zu den Michaelis-Konstanten in Beziehung gesetzt. Bei den geringen Konzentrationen an Ketosäuren nach oraler Zufuhr kann angenommen werden, daß die oxidativen Prozesse in den nichthepatischen Geweben über die Transaminierung überwiegen. Daten über die Wachstumseffizienz von verzweigtkettigen α-Ketosäuren im Vergleich zu den entsprechenden Aminosäuren stimmen mit dieser Vorstellung überein. Bei intravenöser Verabreichung müßten die Voraussetzungen für Transaminierung besser sein als nach oraler Zufuhr. Auf der Basis von Daten aus der Literatur werden die Übertragbarkeit unserer Befunde auf den Menschen und die verschiedenen Faktoren, welche die Effizienz der verzweigten α-Ketosäuren durch Einwirkung auf ihren Stoffwechsel beeinflussen können, diskutiert.
    Notes: Summary Miehaelis-constants and enzyme activities for dehydrogenation and transamination of the three branched chainα-keto acids in liver, kidney, skeletal muscle, and brain of rats are reported. After oral load only 11–22 % of the keto acids pass the liver unchanged. Blood levels in pharmacokinetic and absorption studies are related to the Michaelis-constants. At the low keto-acid concentrations after oral application, dehydrogenation in the non-hepatic tissues is supposed to prevail over transamination. Data on feed efficiency of branched chain α-keto acids reported in the literature support this view. The chance for transamination is better after intravenous administration. The transferability of our data to humans, and various factors influencing the efficiency of branched chain α-keto acids are discussed in connection with data reported in the literature.
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  • 19
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    Cellular and molecular life sciences 41 (1985), S. 1554-1557 
    ISSN: 1420-9071
    Keywords: Immunocytochemistry ; neuropeptide Y ; radioimmunoassay ; rat pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Significant quantities of a newly discovered peptide, neuropeptide Y, were found in the rat pancreas, where they were localized to nerves in the exocrine parenchyma and around arterial and ductal structures. Although unaffected by surgical parasympathectomy, the periarterial and periductal nerves were abolished by chemical sympathectomy, suggesting that NPY is partially costored with sympathetic transmitters in nerve fibers.
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  • 20
    ISSN: 1420-9071
    Keywords: Interferon ; immunomodulator ; catabolism ; pharmacokinetics ; administration routes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary When human recombinant interferon-α2 diluted in saline was injected s.c. into rabbits, the total amount recovered in thoracic lymph was less than 0.4%. Recoveries increased from 2- to 8-fold if interferon was injected in 4% albumin or with hyaluronidase, respectively. Albumin added to interferon acts as an interstitial fluid expander, thus favoring interferon absorption through lymphatics rather than blood capillaries. This strategy may increase the therapeutic index of interferon.
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  • 21
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    Calcified tissue international 12 (1973), S. 313-321 
    ISSN: 1432-0827
    Keywords: Cathepsin D ; Extracellular ; Ossification ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé De la cathepsine D extracellulaire d'origine principalement ostéoblastique a été démontrée par immunohistochimie dans le cartilage en voide de calcification de cultures d'os des membres d'embryons de poulet. L'intérêt de ce fait pour l'ossification est discuté.
    Abstract: Zusammenfassung Es wurde mit einer immunohistochemischen Methode gezeigt, daß extrazelluläres Kathepsin D, welches hauptsächlich aus Osteoblasten gewonnen wurde, Knorpel von kultivierten Knochen von Kükenembryonen mineralisiert. Die Bedeutung dieser Feststellung für den Mechanismus der Knochenbildung wird diskutiert.
    Notes: Abstract Extracellular cathepsin D derived mainly from osteoblasts has been demonstrated immunohistochemically in ossifying cartilage of cultured embryonic chick limb bones. The relevance of this observation to the mechanism of ossification is discussed.
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  • 22
    ISSN: 1432-1351
    Keywords: Photoreception ; Extraretinal Photoreceptor ; Chromophore ; Opsin ; Reptile ; Immunocytochemistry ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Since the beginning of this century evidence has accumulated which demonstrates that non-mammalian vertebrates possess photoreceptors situated deep within the brain. While many attempts have been made to localize these sensory cells, studies have either failed or been inconclusive. In this report we have used several experimental approaches to localize the deep brain photoreceptors of the lizard Anolis carolinensis. Using 3 antibodies that bind vertebrate cone opsins, we have immunolabelled cerebrospinal fluid (CSF)-contacting neurons located at the ventricular border within the nucleus ventromedialis of the septum. Western blot analysis indicates that these antibodies recognized a single 40 kD protein in ocular, anterior brain, and pineal extracts. Immunoblots of rodent brain did not show a similar protein band. We have also identified specific retinoids associated with phototransduction (11-cis and all-trans-3,4-didehydroretinaldehyde) within anterior brain extracts. This combined data provides the most detailed analysis of deep brain photoreceptors in any vertebrate. Consequently, we feel Anolis provides an excellent model to study this unexplored sensory system of the vertebrates.
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  • 23
    ISSN: 1432-1351
    Keywords: Egg laying hormone ; Aplysia ; Binding protein ; Immunocytochemistry ; Reproductive system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A protein solubilized from a membrane preparation of the gonad of Aplysia californica has been isolated by affinity chromatography, using bag cell egg-laying hormone (ELH) as the bound ligand, and partially purified and characterized by gel electrophoresis. The protein has an apparent molecular weight of 52 kDa and consists of two disulfide-linked subunits of about 30 kDa each. The protein is glycosylated and has an acidic pI. Approximately 10–15 μg of this protein can be isolated from a single ovotestis, representing less than 1% of the total protein in the gonad; but the protein could not be detected in buccal mass or body wall, tissues which do not have apparent response to ELH. Antibodies generated against this ELH-binding protein (ELHBP) were used to localize sites in the ovotestis which might contain this molecule and thus represent targets for egg-laying hormone. Immunocytochemical results indicate that the oocytes are a rich source of this protein, since their cytoplasm was the only detectable site of immunoreactivity. Whether this binding protein represents an egg-laying hormone receptor is uncertain, but its prevalence in oocytes suggests that ELH plays a signaling role on these gametes.
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  • 24
    ISSN: 1573-0832
    Keywords: ELISA ; Endodermis ; H. annosum ; Immunocytochemistry ; Root rot ; Vascular tissues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Vascular disintegration mainly of medulla rays of spruce roots is of major significance in root rot disease of spruce caused byH. annosum. Using seedling roots as an experimental model, the possible routes and initial host reactions preceding invasion of vascular tissues was investigated. Transmission electron microscopy showed that penetration through the endodermis was an obvious route but not without host resistance. Using antibodies againstH. annosum hyphal materials, some labelling of vascular tissues remote from sites of fungal colonization suggest the release of fungal secretory products partly active in tissue disintegration. Similarly, intense labelling was also observed in severely colonized host tissues at late stages of infection. Strong labelling recorded at 3 d p.i. mainly on fungal hyphae and scant gold particles on invaded host tissues could imply that induction of host antifungal metabolites may have been a late event. A correlation was found between total antigenic material in root homogenates measured by ELISA, density of tissue labelling by immunocytochemistry and severity of disease symptoms. The importance of this in relation to diagnosis of biotic root rot diseases in the field is discussed.
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  • 25
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    Mycopathologia 125 (1994), S. 107-117 
    ISSN: 1573-0832
    Keywords: Aflatoxin B1 ; Immunocytochemistry ; Regeneration ; Tissue culture ; Tobacco plantlets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effects of aflatoxin B1, (0.5–25 µg ml−1) on in vitro root and shoot development in young tobacco explants were investigated. Despite an initial apparent stimulatory effect on most measured parameters at 0.5 µg ml−1 AFB1, the number of leaves, root and leaf mass per plantlet were progressively inhibited with increasing AFB1 concentration. The number of explants developing roots was reduced to 34% at the highest (25 µg ml−1) AFB1 concentration, following 3 weeks exposure to the toxin. Leaf chlorophyll content at this toxin concentration was significantly lower than that measured for control plantlets. Thin layer chromatography confirmed the absorption of AFB1 by the plantlets. Using immunocytochemical techniques, AFB1 was immunolocated predominantly in the vacuoles, the nucleus and the cytoplasm (possibly intravesicularly). The results are discussed in terms of this immunolocation within the cell.
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  • 26
    ISSN: 1432-041X
    Keywords: Vitellin ; Yolk granule ; Yolk protein ; Silkworm ; Embryogenesis ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Vitellin was purified from eggs of the silkworm,Bombyx mori, by a new method in which vitellin was extracted from isolated yolk granules. The purified vitellin had a molecular weight of 540,000. An antibody against purified vitellin was prepared in rabbits. It reacted with the hemolymph vitellogenin as well as with purified vitellin, but not with other proteins in the hemolymph or in the extract from yolk granules. The anti-vitellin IgG was used to immunocytochemically locate vitellin in theBombyx non-diapause egg during early developmental stages. In the egg, just after oviposition, vitellin was located in internal yolk granules and in small yolk granules of the periplasm. During the early developmental stages studied, vitellin was not metabolized uniformly throughout the egg. The vitellin of the internal yolk granules located at the posterior-dorsal part and of the small peripheral yolk granules was utilized in 16 h and 2 days, respectively, after oviposition. A thin, very vitellin-poor layer was located between the periplasm and the vitellin-rich interior in the newly laid egg. it was always in close contact with the periphery where blastoderm and germ-band cells developed.
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  • 27
    ISSN: 1432-041X
    Keywords: Major haemolymph proteins ; Development ; Cuticle ; Immunocytochemistry ; Ceratitis capitata
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The developmental profile of the major haemolymph proteins (ceratitins) inCeratitis capitata was studied. Ceratitin concentration in the haemolymph decreases dramatically during the last days of pupal life, while the amounts of ceratitins in whole organism extracts remain unchanged. By electrophoretic, immunological and immunofluorescence techniques it was revealed that ceratitins are reabsorbed by the fat body and a fraction of them is deposited in the cuticle. The possible role of ceratitins is discussed.
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  • 28
    ISSN: 1432-041X
    Keywords: Sea urchin ; Jelly coat ; Accessory cell ; Oogenesis ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The immunocytochemical localization of the egg-jelly macromolecule, a fucose sulphate glycoconjugate (FSG) that induces the acrosome reaction in spermatozoa, was investigated in ovaries of the sea urchin Hemicentrotus pulcherrimus by use of a polyclonal antibody. The polyclonal antibody reacted with the accessory cells and oocytes in the ovarian lumen. In the accessory cells, evidence of an intense immunohistochemical reaction was observed in many globules of variable density. Products of the specific immunohistochemical reaction were frequently observed in the surface region of oocytes, at a distance from the ovarian wall. At the ultrastructural level, the polyclonal antibody was found to react with the material present in the vacuole-like structures of the globules in the accessory cells. Many gold particles, demonstrating specific immunolabelling, were associated with well-developed microvilli on the vitellogenic oocytes. In the mature oocytes, intense labelling was observed in the jelly coat but not in the vitelline coat. By contrast, oogonia and early oocytes were barely labelled. Quantitative data indicated that the extent of immunolabellings in the surface region of oocytes was very high in the vitellogenic and mature oocytes. In all cases, neither the oocyte cytoplasm nor the subcellular organelles were labelled. These results suggest that FSG is produced by the accessory cells and is deposited initially on the surface of vitellogenic oocytes for the formation of jelly. These findings may provide a new insight into the role of the accessory cells in the reproductive process of the sea urchin.
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  • 29
    ISSN: 1432-041X
    Keywords: Sea urchin ; Egg jelly ; Ovary ; Development ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In the sea urchin Hemicentrotus pulcherrimus, the egg-jelly macromolecule, a fucose sulphate glycoconjugate (FSG) that induces the acrosome reaction in spermatozoa, originates from the accessory cells in the ovary. In the present study we examined the seasonal variations in the distribution of FSG in the ovary by immunocytochemistry with a polyclonal antibody. An enzyme-linked immunosorbent assay indicated that FSG was present in supernatants of extracts of ovaries throughout the development of the ovary. However, the immunohistochemical study showed that there are marked seasonal changes in the distribution of FSG in ovaries. The polyclonal antibody reacted strongly with globules of accessory cells before the beginning of the breeding season (August to December). During the breeding season (February to April), the immunohistochemical reaction was found on the surface of oocytes but was weak in the accessory cells. At the ultrastructural level, the antibody reacted with globules of variable density in accessory cells. Intense immunolabelling was observed in the vacuole-like structures of the globules. Sometimes, products of the specific immunocytochemical reaction were found in the Golgi apparatus in these globules. Quantitative examination indicated that FSG was actively produced by the accessory cells from the late non-breeding season to the pre-breeding season. These results suggest that there are marked seasonal variations in the production of FSG by the accessory cells in the sea urchin ovary. These findings also provide new evidence that accessory cells exhibit dynamic changes during the reproductive process in the sea urchin.
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  • 30
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    Cellular and molecular life sciences 41 (1985), S. 1340-1342 
    ISSN: 1420-9071
    Keywords: Immunocytochemistry ; calmodulin ; secretory granules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Calmodulin is a regulator of several calcium-dependent cellular processes. It has been suggested that it plays a role in the mechanism of secretion. Employing an indirect immunoperoxidase technique at the light microscope level, this study demonstrates the presence of calmodulin in several exocytotic cells (mast cells, thyroid follicular cells, neurohypophyseal neurosecretory terminals, pancreaticβ-cells and pancreatic acinus cells) in rat and man. The positive staining reaction for calmodulin was granular and at least in the case of rat mast cells it appeared to be associated with the granule membrane.
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  • 31
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    Trees 13 (1999), S. 138-151 
    ISSN: 0931-1890
    Keywords: Key words Cytoskeleton ; Immunocytochemistry ; Model systems ; Populus ; Secondary vascular system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract  Trees represent a, probably the, major component of the biosphere and have a unique place in the history of Mankind. One of their most fascinating features is the process of secondary growth which is effected principally by the secondary vascular system, the developmental continuum of secondary phloem, vascular cambium, and secondary xylem. However, for too long assumptions about the developmental biology of trees have had to be based upon studies of primary growth systems within annual, herbaceous species because study of the secondary vascular system had been largely ignored. Even when attempts are made to understand some of the most fundamental features of the secondary vascular system, such as xylogenesis, the current model system, isolated Zinnia mesophyll cells, is not entirely appropriate to the situation in the intact tree. Some deficiencies of the Zinnia system are discussed, and the advantages of the genus Populus as a model for study of the hardwood secondary vascular system are considered. Some of the new approaches which are poised to lead to significant advances in our knowledge of the cell bio-logy of the secondary vascular system of trees – spe-cifically of the cell wall, the plasmalemma, and the cytoskeleton – are discussed. The value of one of these new techniques – immunocytochemistry – is demonstrated by a consideration of recent work on the role of the cytoskeleton in the hardwood secondary vascular system.
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  • 32
    ISSN: 1432-0827
    Keywords: Androgen Receptor ; Osteoclast ; Mouse ; Immunocytochemistry
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    Topics: Biology , Medicine , Physics
    Notes: Summary Expression of androgen receptor (AR) in mouse osteoclast-like multi-nucleated cells (OCs) was examined with immunocytochemical techniques. Murine OCs were obtained by co-culturing mouse osteoblastic cells and bone marrow cells. Three preparations of polyclonal anti-AR antibody which were raised in rabbit against different parts of the human AR were employed for the experiments. Specific staining for AR was demonstrated in the nuclei and the perinuclear area of mouse OCs. This is the first report demonstrating the presence of AR in osteoclast-like cells.
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  • 33
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    Calcified tissue international 24 (1977), S. 223-229 
    ISSN: 1432-0827
    Keywords: Enamel-cementum-morphology ; Immunocytochemistry ; Biochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The continuously erupting rabbit incisor tooth is normally thought of as having an enamel covered “crown” on its labial surface and a cementum covered “root” on its lingual surface. We have examined both surfaces of continuously erupting rabbit incisor teeth taken from near term embryos by a variety of means, including transmission and scanning electron microscopy, biochemical fractionation, and immunohistochemistry. In all cases, we could detect no qualitative difference in the early extracellular matrices taken from the labial and lingual surfaces of the teeth. Both matrices were shown to be composed of dentin and enamel, although the thickness and geometry of the enamel matrix on the lingual surface was somewhat different from that on the labial surface.
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  • 34
    ISSN: 1432-0827
    Keywords: Growth hormone ; Growth hormone receptor ; Odontogenesis ; Bone remodeling ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Growth hormone (GH) may regulate tooth formation and bone remodeling associated with tooth eruption. This study reports the distribution of growth hormone receptor/binding protein in developing rat molars and adjacent alveolar bone by immunocytochemistry using well-characterized anti-growth hormone receptor monoclonal antibodies. These tissues represent an excellent model for studying the ontogenic changes that occur in odontogenic and osteogenic cells, as these cells are found in linear arrays displaying the various stages of morphological and functional differention, and differentiated function. Immunoreactivity was first seen in precementoblasts in contact with the epithelial root sheath, and preodontoblasts. However, growth hormone receptor immunoreactivity was associated primarily with the cytoplasm of odontogenic and osteogenic cells forming their respective matrices. Thus, cementoblasts and odontoblasts at sites of new matrix formation showed intense immunoreactivity whereas cementocytes and mature odontoblasts at later stages of tooth development were nonreactive. Osteoblasts engaged in intramembranous ossification in the alveolar bone were positive, although osteocytes and endosteal cells were immunonegative. Osteoclasts at sites of alveolar bone remodeling resorption were also immunopositive. These patterns of receptor expression parallel the ontogenic sequences of odontogenic and osteogenic cells and suggest that GH promotes the functional state of these cells. Our results also imply that GH may influence differentiation or differentiated functions associated with odontogenesis, osteogenesis, and bone remodeling independent of systemic insulin-like GF-I.
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  • 35
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    Histochemistry and cell biology 106 (1996), S. 9-17 
    ISSN: 1432-119X
    Keywords: Silver enhancement ; Immunogold-silver staining ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The immunogold silver staining method (IGSS) is widely used as a sensitive and specific immunohistochemical visualisation technique. IGSS involves the specific deposition of metallic silver at the site of immunogold labelling and provides a means of visualisation at low magnification by light or electron microscopy. Silver developers for IGSS rapidly deposit metallic silver only at the site of heavy metals, including gold and silver, because of their catalytic activity. The developing solution contains the silver ions and reducing agent necessary for this reaction. Using different silver salts as ion donors and by selecting an appropriate temperature and pH, visible amounts of silver can be deposited in a few minutes at the site of colloidal gold labelling while little non-specific background deposition occurs. Inclusion of protective colloids in the solution can also be used to control the reaction. Although studies of the chemical basis of silver deposition around unlabelled colloidal gold date back to 1939, immunogold enhancement by silver was established in 1983. The IGSS method evolved from the combination of disparate photographic, histochemical and immunogold techniques which have been effectively combined and optimised over the last 10 years to provide a visualisation system which is well suited to many immunohistochemical studies.
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  • 36
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    Histochemistry and cell biology 106 (1996), S. 9-17 
    ISSN: 1432-119X
    Keywords: Key words Silver enhancement ; Immunogold-silver staining ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The immunogold silver staining method (IGSS) is widely used as a sensitive and specific immunohistochemical visualisation technique. IGSS involves the specific deposition of metallic silver at the site of immunogold labelling and provides a means of visualisation at low magnification by light or electron microscopy. Silver developers for IGSS rapidly deposit metallic silver only at the site of heavy metals, including gold and silver, because of their catalytic activity. The developing solution contains the silver ions and reducing agent necessary for this reaction. Using different silver salts as ion donors and by selecting an appropriate temperature and pH, visible amounts of silver can be deposited in a few minutes at the site of colloidal gold labelling while little non-specific background deposition occurs. Inclusion of protective colloids in the solution can also be used to control the reaction. Although studies of the chemical basis of silver deposition around unlabelled colloidal gold date back to 1939, immunogold enhancement by silver was established in 1983. The IGSS method evolved from the combination of disparate photographic, histochemical and immunogold techniques which have been effectively combined and optimised over the last 10 years to provide a visualisation system which is well suited to many immunohistochemical studies.
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  • 37
    ISSN: 1432-2048
    Keywords: Immunocytochemistry ; Lectin (localization) ; Phaseolus (lectin) ; Phytohemagglutinin ; Seed (lectin)
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    Topics: Biology
    Notes: Abstract We have examined the properties and subcellular localization of phytohemagglutinin (PHA), the major lectin of the common bean (Phaseolus vulgaris.), in the axis cells of nearly mature and imbibed mature seeds. On a protein basis the axis contained about 15% as much PHA as the cotyledons. Localization of PHA was done with an indirect immunolabeling method (rabbit antibodies against PHA, followed by colloidal gold particles coated with goat antibodies against rabbit immunoglobulins) on ultra-thin cryosections which were embedded in plastic on the grids after the immunolabeling procedure. The embedding greatly improved the visualization of the subcellular structures. The small (4 nm) collodial gold particles, localized with the electron microscope, were found exclusively over small vacuoles or protein bodies in all the cell types examined (cortical parenchyma cells, vascular-bundle cells, epidermal cells). The matrix of these vacuoles-protein bodies appears considerably less dense than that of the protein bodies in the cotyledons, but the results confirm that in all parts of the embryo PHA is localized in similar structures.
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  • 38
    ISSN: 1432-2048
    Keywords: Glycine (xanthine dehydrogenase) ; Immunocytochemistry ; Polyclonal antibody ; Root nodule ; Xanthine dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Xanthine dehydrogenase (XDH, EC 1.2.1.37) was purified from root nodules of soybean (Glycine max) and used to prepare a polyclonal rabbit antiserum. Monospecificity of this antiserum was ascertained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoprecipate. During root nodule development of soybean, only one form of XDH was detected on an immunological basis. Titration of XDH by immunoelectrophoresis showed that a remarkable increase in the amount of XDH occurred between two and four weeks after inoculation, in parallel with the increase in enzyme activity. Localization of XDH by immunofluorescence indicated that the enzyme was present exclusively in uninfected cells where it appeared to be associated with discrete organellels
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  • 39
    ISSN: 1432-2048
    Keywords: Avena ; Immunocytochemistry ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phytochrome of oat (Avena sativa L., cv. Garry) coleoptile cells in the red-light-absorbing form, Pr, is diffusely distributed while after conversion to the far-red-light-absorbing form, Pfr, it is observed only in very small areas within the cell. Comparison of phytochrome photoversibility measurements to the distribution of the pigment within the cell indicates that the spectral assay is not influenced by the observed compartmentalization of the chromoprotein. However, the observed compartmentalization of phytochrome is correlated with a loss in spectrophotometrically detectable Pr.
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  • 40
    ISSN: 1432-2048
    Keywords: Cotyledons ; Endoplasmic reticulum ; Ferritin labeling ; Immunocytochemistry ; Phaseolus ; Protein (reserve) ; Reserve protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The ultrastructure of the storage parenchyma cells of the cotyledons of developing bean (Phaseolus vulgaris L.) seeds was examined in ultrathin frozen sections of specimens fixed in a mixture of glutaraldehyde, formaldehyde and acrolein, infused with 1 M sucrose, and sectioned at-80° C. Ultrastructural preservation was excellent and the various subcellular organelles could readily be identified in sections which had been stained with uranyl acetate and embedded in Carbowax and methylcellulose. The cells contained large protein bodies, numerous long endoplasmic reticulum cisternae, mitochondria, dictyosomes, and electron-dense vesicles ranging in size from 0.2 to 1.0 μm. Indirect immunolabelling using rabbit immunoglobulin G against purified phaseolin (7S reserve protein), and ferritin-conjugated goat immunoglobulin G against rabbit immunoglobulin G was used to localize phaseolin. With a concentration of 0.1 mg/ml of anti-phaseolin immunoglobin G, heavy labeling with ferritin particles was observed ober the protein bodies, the cisternae of the endoplasmic reticulum, and the vesicles. The same structures were lightly labeled when the concentration of the primary antigen was 0.02 mg/ml. Ferritin particles were also found over the Golgi bodies. The absence of ferritin particles from other organelles such as mitochondria and from areas of cytoplasm devoid of organelles indicated the specificity of the staining, especially at the lower concentration of anti-phaseolin immunoglobulin G.
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  • 41
    ISSN: 1432-2048
    Keywords: Immunocytochemistry ; (PEP carboxylase) ; PEP carboxylase ; Sorghum
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    Topics: Biology
    Notes: Abstract The localization of phosphoenol pyruvate carboxylase (EC 4.1.1.3.1.) in the leaf cells of Sorghum vulgare was investigated by using three techniques: the conventional aqueous and non aqueous methods gave conflicting results; the immunocytochemical techniques clearly showed that the enzyme is predominantly located in the cytoplasm of mesophyll cells.
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  • 42
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    Sexual plant reproduction 5 (1992), S. 89-100 
    ISSN: 1432-2145
    Keywords: Actin ; Cytoskeleton ; Generative cell ; Immunocytochemistry ; Microtubule ; Mitosis ; Phragmoplast ; Pollen ; Rhodamine phalloidin ; Sperm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Disagreement has arisen over the presence of actin-containing microfilaments (Mfs) in angiosperm generative cells and sperm (GSP). In order to address this issue, we subjected GSP of Tradescantia virginiana, Nicotiana tabacum and Rhododendron laetum to a series of localizations using different antiactins, rhodamine phalloidin and antimyosin. Coordinate staining with antitubulin and Hoechst 33258 defined the status of the microtubule (Mt) cytoskeleton and stages of generative cell division. Additional experiments utilized cytochalasin D (CD). In no instance could Mfs be detected in GSP of the three species. Instead, Mfs seen at the periphery of GSP appear to be continuous with vegetative Mfs and thus are in the vegetative cytoplasm. Mfs are not seen in the constriction zone of dividing T. virginiana generative cells, nor are they indicated in the phragmoplast of N. tabacum and R. laetum. Myosin localizations reveal punctate staining in the vegetative cytoplasm and a thin line of fluorescence around the the outside of the generative cell. While CD seems to delay generative cell division, cytokinesis still takes place. CD-induced Mf fragments are evident in the vegetative cytoplasm but not in GSP. The weight of evidence therefore indicates that GSP do not contain Mfs. The implications of this conclusion for the behavior of GSP and the mechanism of cytokinesis in dividing generative cells are considerable.
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  • 43
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    European journal of clinical pharmacology 32 (1987), S. 631-634 
    ISSN: 1432-1041
    Keywords: salbutamol ; albuterol ; pharmacokinetics ; bioavailability ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Salbutamol was administered to sixteen healthy male volunteers intravenously and by mouth in liquid, tablet, and capsule form using a Latin-Squares design. Pharmacokinetic parameters from intravenous data were similar to previously reported values obtained with oral administration, with a mean terminal half-life of 3.8 h and a mean clearance of 439 ml·min−1·1.73 m−2. Peak plasma concentrations of 10–20 ng·ml−1 were obtained 1–3 h following oral administration. The absolute bioavailability of each of the oral preparations was 44%. While statistically significant differences in lag time and time to peak concentration were noted among the various oral preparations, the drug is rapidly absorbed in all three dosage forms and the observed differences are unlikely to be of clinical significance.
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  • 44
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    European journal of clinical pharmacology 42 (1992), S. 101-105 
    ISSN: 1432-1041
    Keywords: Rufloxacin ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma and urine kinetics of rufloxacin were assessed in healthy volunteers after single (100, 200, 400 and 800 mg) and multiple (300 mg followed by 150 mg daily, Group 1, and 400 mg followed by 200 mg daily, Group 2) oral doses. The kinetics of a single oral dose of 800 mg was assessed in fasting and non-fasting subjects to assess the influence of food intake on drug absorption. The AUCs were 134, 266 and 375 μg · h · ml−1 after 100, 200 and 400 mg, respectively. The AUC after 800 mg p. o. was 715 μg · h · ml −1 in fasting subjects and 614 μg · h · ml−1 in non-fasting subjects. The parameters of the model and the mean renal clearance values indicated some departure from linearity in rufloxacin kinetics. After multiple doses the plasma drug levels during the 6th treatment day were similar to those after the first dose in Group 1 and were about 30–40% higher after the first dose in Group 2. The half-lives after the last dose were much shorter than those estimated in the single dose studies (33–36 h and 50–80 h, respectively).
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  • 45
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    European journal of clinical pharmacology 42 (1992), S. 535-538 
    ISSN: 1432-1041
    Keywords: Meropenem ; Carbapenem ; pharmacokinetics ; uraemia ; haemodialysis
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 24 or 48 h. Meropenem concentrations in plasma and urine were measured by a microbiological assay. The mean peak plasma concentration of meropenem ranged from 28 to 40 μg·ml−1 and was not affected by the degree of renal impairment. The terminal half-life of meropenem was approximately 1 h in subjects with normal kidney function and it was proportionately increased as renal function decreased. A significant linear relationship between total body clearance and creatinine clearance as well as between renal clearance and creatinine clearance was observed. The mean apparent volume of distribution at steady state was not significantly altered in uraemic patients. The mean cumulative urinary recovery of meropenem in healthy volunteers was 77% of the administered dose and it was significantly decreased in patients with renal impairment. Haemodialysis shortened the elimination half-life, from 9.7 h during the predialysis period to 1.4 h during the dialysis period. The dose of meropenem should be reduced in relation to the decrease in creatinine clearance.
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  • 46
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    European journal of clinical pharmacology 34 (1988), S. 179-186 
    ISSN: 1432-1041
    Keywords: ceftazidime ; pharmacokinetics ; elderly patients ; young volunteers ; acute infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ceftazidime have been investigated after single and multiple i.v. doses in 9 young healthy male volunteers and 15 elderly male patients with acute bacterial infections. All subjects had normal, age-correlated glomerular function. Distribution and elimination in young volunteers were unaffected by posture and were similar to what has been reported earlier. In contrast, elderly patients had longer t1/2β (3.1 vs 1.9 h), larger AUC (414.0 vs 276.6 h·mg/l), lower total and renal clearances, reduced urinary recovery over 12 h and enlarged Vss. Total serum clearance of ceftazidime was closely correlated with the51Cr-EDTA clearance. There was no significant change in51Cr-EDTA clearance after seven days of treatment. A reduction in the dose of betalactam antibiotics eliminated by the kidney is advisable in elderly patients with an acute bacterial infection.
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  • 47
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    European journal of clinical pharmacology 42 (1992), S. 559-560 
    ISSN: 1432-1041
    Keywords: Mefloquine ; Thai subjects ; pharmacokinetics ; Primaquine ; drug interaction ; adverse effects
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  • 48
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    European journal of clinical pharmacology 39 (1990), S. 395-397 
    ISSN: 1432-1041
    Keywords: atropine ; exercise ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven healthy males (19–32 y) underwent each of four separate conditions in a repeated measures design. Five of these subjects underwent an additional trial. In four of five trials subjects received 2.0 mg atropine sulfate intramuscularly in the anterolateral portion of the left thigh: at rest (T1); following completion of a single exercise (Ex) bout (T2), (Each bout consisted of 25 min of stationary cycling at 40% VO2 max with 5 min of seated rest), prior to three Ex bouts (T3) and following one and prior to three Ex bouts (T5). Trial 4 (T4) was the same as T3 with the substitution of a saline placebo. Serum samples were collected over a 12 h period and atropine concentration was determined by RIA. Ex trials were compared to T1. Ex prior to atropine (T2) significantly decreased the mean volume of distribution (Vz, 278 vs 2321). Ex in T3 significantly decreased the serum half life (t1/2, 4.2 vs 3.5 h), Vz (278 vs 1981), and clearance (CL, 763 vs 638 ml·min−1) and significantly increased the peak concentration (Cp, 6.7 vs 12.3 ng·ml−1) and area under the curve (AUC, 44.1 vs 53.1 ng·ml−1). In T5, Ex significantly decreased the t1/2 (3.4 h), Vz (182 l) and CL (575 ml·min−1) and significantly increased the absorption rate constant (ka, 0.482 vs 1.1 min−1), elimination rate constant (ke, 0.0012 vs 0.0015 min−1), Cp (14 ng·ml−1) and AUC (53.3 ng·h·ml−1). These results demonstrate that moderate Ex either prior to and/or immediately following drug administration has the capacity to significantly modify atropine pharmacokinetics.
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  • 49
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    European journal of clinical pharmacology 42 (1992), S. 689-691 
    ISSN: 1432-1041
    Keywords: Diphemanil methylsulphate ; pharmacokinetics ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of oral diphemanil methylsulphate have been evaluated in six healthy male volunteers. Absorption of the drug was slow (tmax=2 to 4 h), the mean half-life was 8.35 h, and the amount of the drug recovered in urine within 48 h ranged from 0.6 to 7.4% of the administered dose. The results suggest low bioavailability, assuming that the drug is poorly metabolized.
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  • 50
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    European journal of clinical pharmacology 42 (1992), S. 693-694 
    ISSN: 1432-1041
    Keywords: Loperamide ; loperamide oxide ; diarrhoea ; pharmacokinetics ; dose-proportionality
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of loperamide, after oral administration of increasing doses (1 to 16 mg) of loperamide oxide, has been investigated in 10 healthy male volunteers, using a randomised cross-over design. Comparison of the maximum plasma loperamide concentration and AUC demonstrated that the bioavailability of loperamide was proportional to the dose of loperamide oxide administered.
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  • 51
    ISSN: 1432-1041
    Keywords: Alpidem ; Anxiolytics ; pharmacokinetics ; tolerance ; metabolites ; sedation ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, placebo-controlled, crossover experiment in 21 healthy male volunteers, aged 19 to 27 y, the pharmacokinetics and tolerance of the new anxiolytic drug alpidem (SL80.0342) and its three major metabolites were studied after single doses of 25, 50, 100 and 200 mg. Plasma concentrations of alpidem (in 20 subjects) and metabolites (in 6 subjects) were measured by HPLC over a period of 54 h after dosing. Cmax, tmax and AUC(0–54) and, when possible, t1/2 were determined for alpidem and metabolites and the dose linearity of the parameters was investigated. The time to peak of alpidem was dose independent in most subjects and was short (1–4 h); the mean values at the four dosing levels were 1.9, 1.7, 1.6 and 1.8 h. The peak concentration increased with the dose, the mean values being 17, 34, 88 and 115 ng · ml−1, respectively. In 50% of the subjects cmax tended to stabilize between the 100 and 200 mg dose. Dose linearity was also present for the AUC, which plateaued between the 100 and 200 mg dose in only 3 out of 20 subjects; the mean AUC was 119, 281, 669 and 1117 ng · ml−1 · h, respectively. The apparent half-life of elimination appeared to be dose independent, mean values at the increasing dosing levels being 18.7, 19.9, 18,1 and 17.9 h. A similar relationship between the kinetics parameters and dose of the alpidem was observed for the metabolites SL83.0912, SL80.0522 and SL83.0725. The formation of metabolites was not saturated as their AUCs relative to corresponding alpidem AUCs were not dose related. Thus the kinetics of alpidem and its three major metabolites were linear after doses of 25 to 200 mg. The drug was well tolerated by most of the subjects. Sedation and dizziness occurred mainly after the 100 and 200 mg doses.
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  • 52
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    European journal of clinical pharmacology 43 (1992), S. 67-75 
    ISSN: 1432-1041
    Keywords: Morphine ; Patient-controlled analgesia ; opioids ; pharmacokinetics ; bolus-elimination-transfer ; computer-assisted continuous infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bone marrow transplant patients having severe, prolonged oral mucositis pain (expected to last for one to three weeks) used a computer-controlled infusion system to self-administer morphine for pain control. Individual patient pharmacokinetic information, derived from a pretreatment bolus morphine dose, was used in a new bolus-elimination transfer algorithm to produce rapid adjustments of steady plasma morphine concentrations when the patient requested more or less drug. We evaluated the performance characteristics (bias and precision) of this pharmacokinetically based patient-controlled analgesic infusion system (PKPCA) in a group of 15 cancer patients over six to 14 days. Although we found a three- to fivefold pharmaco-kinetic variability in the tailoring morphine dose data, the PKPCA system was free of systematic bias (insignificant overall prediction error) during the patient-controlled infusions in this study population. The absolute prediction error was 19.9% for the group on the first study day and 25.6% over the entire study period (aggregate results; 6–14 days of continuous use). Two-thirds of the patients exhibited no bias throughout the study period, and individual bias in the others was symmetrically distributed (three patients with underpredictions and two overpredicted). Magnitude of prediction error during the patient-controlled morphine infusions was not related to the magnitude of pharmacokinetic deviation of individual subjects from group parameters. Our results indicate that this PKPCA system provides accurate control of plasma morphine concentration when used by patients to self-administer opioid for prolonged pain relief continuously over 1 to 2 weeks. Use of individual pharmacokinetic information, instead of population parameters, may account for superior performance characteristic of this computer-assisted continuous drug infusion system.
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  • 53
    ISSN: 1432-1041
    Keywords: Indomethacin ; steady-state ; pharmacokinetics ; elderly
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady-state pharmacokinetic profile of indomethacin was examined in twelve healthy volunteers (4 m, 8 f; 20–34 y) and in 12 elderly subjects (7 m, 5 f; 70–88 y). Two formulations of indomethacin were examined, providing duplicate data for each subject group. The subjects received each formulation of indomethacin (25 mg tid) for 6 days in a single blind crossover fashion. On day 7, after an overnight fast, a final 25 mg dose of indomethacin was given and plasma concentrations measured over the following 12 h. Kinetic parameters Cpmin, tmx and AUC (0–12 h) were determined. There were no differences in the pharmacokinetic parameters between young and elderly subjects or between data for the two formulations of indomethacin. AUC values (μg · ml−1 · h), for example, for the two formulations in the young subjects were 5.85 and 6.85 while the values for the elderly subjects were 6.55 and 6.50 respectively. When each treatment period was considered independently there was a significant difference between young and elderly subjects with regard to compliance. The rates of non compliance (over and under compliance) using a capsule count technique were, however, low with a mean maximum value of 5.8% being recorded for the elderly subjects.
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  • 54
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    European journal of clinical pharmacology 41 (1991), S. 449-452 
    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; Caffeine ; pharmacokinetics ; P-450 mono-oxygenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Diabetes may alter the pharmacokinetics of aminopyrine and antipyrine, which are used to assess liver function. Caffeine has recently been used to test liver function, but the effect of diabetes on caffeine kinetics is not known. The kinetics of caffeine has been examined in patients with decompensated Type I and Type II diabetes and in two age- and sex-matched control groups. In both types of diabetes the apparent caffeine clearance, half-life, and apparent volume of distribution were similar to controls. It is concluded that decompensated diabetes does not influence the cytochrome P-448 mono-oxygenase system responsible for caffeine metabolism.
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  • 55
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    European journal of clinical pharmacology 42 (1992), S. 231-233 
    ISSN: 1432-1041
    Keywords: Isradipine ; Haemodialysis ; pharmacokinetics ; dialysability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of isradipine, a calcium-channel blocker, have been studied in eight patients on chronic haemodialysis. A single oral dose of 5 mg was administered on both a non-haemodialysis and a haemodialysis day and the plasma concentrations of isradipine were analyzed. The mean cmax, tmax, AUC, and t1/2 in plasma on the non-haemodialysis day were 5.2 ng·ml−1, 1.4 h, 23.8 ng·h·ml−1, and 3.1 h, respectively. The dialysis clearance of isradipine was negligible (5.0 ml·min−1). The t1/2 values during haemodialysis were not significantly different from those observed during the same period post dose on the non-haemodialysis day. The study demonstrates that supplemental doses of isradipine are not necessary in these patients since isradipine is not significantly removed by haemodialysis.
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  • 56
    ISSN: 1432-1041
    Keywords: Liver cirrhosis ; Spirapril ; ACE inhibitor ; pharmacokinetics ; haemodynamic effects ; liver function tests
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensinconverting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n=10), in patients with chronic, non-cirrhotic liver disease (n=8) and in a control group of healthy subjects (n=16). The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 μg·h·l−1, 923 μg·h·l−1 and 1300 μg·h·l−1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively. Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h−1 in patients vs. 2.00 h−1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls. Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients.
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  • 57
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    European journal of clinical pharmacology 40 (1991), S. 593-597 
    ISSN: 1432-1041
    Keywords: Dopamine ; Newborns ; critically ill patients ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5–20 μg · kg−1 · min−1, for presumed or proven sepsis and hypotensive shock. Steady-state concentrations of dopamine ranged from 0.013–0.3 μg/ml. Total body clearance averaged 115 ml · kg−1 · min−1. The apparent volume of distribution and elimination half life averaged 1.8 1 · kg−1 and 6.9 min, respectively. No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants.
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  • 58
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    European journal of clinical pharmacology 40 (1991), S. 619-624 
    ISSN: 1432-1041
    Keywords: Inulin ; pharmacokinetics ; half life ; distribution ; concentration-dependent clearance ; healthy subjects ; chronic renal failure
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of inulin was studied in 30 healthy male and 10 healthy female volunteers, and 10 patients with stable chronic renal failure (mean creatinine clearance 45 ml·min−1) following intravenous infusion of 70 mg·kg−1 over 5 min. Plasma concentrations fell rapidly initially but the rate of decline decreased continuously over 8 h and a linear terminal elimination phase could not be identified. Inulin was excreted rapidly by the subjects with normal renal function and 97.3% of the dose was recovered in the urine in 8 h. There was a progressive highly significant fall in the renal clearance of inulin after 2 h as plasma concentrations fell below about 150 mg·l−1. Six to 8 h after administration the clearance was less than 50% of the initial value in the healthy volunteers and the corresponding fall in the renal patients was 33%. The concentration-dependent renal clearance of inulin was confirmed in “step-up” and “step-down” constant infusion studies in which clearances were measured at mean plasma concentrations ranging from 35.2 to 186.7 mg·l−1. These studies virtually excluded time, changes in posture and urine flow rate as important factors. There was no statistically significant fall in clearance during the first 2 h and kinetic analysis was based on data obtained over this time. Under these conditions the mean plasma half life, volume of distribution (Vss) and total body clearance of inulin in the healthy males, healthy females and patients with chronic renal failure were 73.2, 65.5 and 172.4 min, 10.5, 9.6 and 8.81·70 kg−1 and 113.3, 111.5 and 43.3 ml·min−1·70 kg−1 respectively. There were no sex differences in any of the kinetic variables. The mechanism of the concentration-dependent clearance of inulin is unknown but the findings are consistent with saturable renal tubular reabsorption. Care is required with the use of inulin for measurement of the glomerular filtration rate by the single injection technique.
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  • 59
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    European journal of clinical pharmacology 40 (1991), S. 631-633 
    ISSN: 1432-1041
    Keywords: Mefloquine ; ampicillin ; Thai subjects ; pharmacokinetics ; enterohepatic recycling ; drug interaction ; adverse effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single oral dose of mefloquine given either alone or with ampicillin has been studied in 8 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with ampicillin (1648 vs 1228 ng·ml−1), as well as a significantly reduced terminal half life (15.3 vs 17.7 days), mean residence time (20.1 vs 23.4 days) and volume of distribution at steady state (14.1 vs 19.4 l·kg−1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 5 days was significantly increased by ampicillin (4.86 vs 3.27 μg·ml−1 day). These changes in mefloquine disposition after antibiotic treatment may be due both to an increase in fractional bioavailability and a reduction in the enterohepatic recycling of mefloquine.
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  • 60
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    European journal of clinical pharmacology 40 (1991), S. 637-638 
    ISSN: 1432-1041
    Keywords: Roxatidine acetate ; sucraflate ; pharmacokinetics
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  • 61
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    European journal of clinical pharmacology 45 (1993), S. 357-361 
    ISSN: 1432-1041
    Keywords: Circadian rhythms ; Indomethacin ; Ketoprofen ; pharmacokinetics ; time-varying models ; nonsteroidal anti-inflammatory drugs
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A one-compartment model with first-order absorption has provided good fits to five sets of indomethacin data and four sets of ketoprofen data taken at different times of day. There was substantial variation in the model parameters with time of administration and most of the features of this variation applied equally to both drugs. From the data examined, the source of variation appears to be mainly in the absorption phase and this was confirmed using a chronokinetic analysis, in which simultaneous fits were obtained with time-variant rate parameters. However, there may also be circadian variation in protein binding. The danger of quoting parameter values for either of these two drugs based on administration at a single time of day has been illustrated, and this may well be true for other drugs.
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  • 62
    ISSN: 1432-1041
    Keywords: Gamma-hydroxybutyric acid ; pharmacokinetics ; dose-proportionality
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg−1. The AUC increased disproportionately with the dose and so the apparent oral clearance decreased significantly as the dose was increased, whereas the terminal half-life and mean residence time increased. The peak plasma concentrations normalised to the lowest dose fell significantly with increasing doses, whilst the corresponding peak times increased. These findings suggest that both the oral absorption and the elimination of GHB are capacity-limited processes. GHB did not bind to significant extent to plasma proteins over the therapeutic concentration range. The pharmacokinetic parameters in healthy volunteers were not significantly different from those previously observed in alcohol-dependent patients with compensated alcoholic liver disease.
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  • 63
    ISSN: 1432-1041
    Keywords: Glyceryl trinitrate spray ; pharmacokinetics ; a/b-ratio ; pulmonary artery diastolic pressure ; finger pulse curve ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course and the magnitude of the effect of glyceryl trinitrate (GTN) on central venous (pulmonary artery diastolic pressure-PAPd) and peripheral arterial (a/b-ratio of the finger pulse wave) haemodynamics were compared in a randomized double-blind cross-over study in 12 patients suffering from congestive heart failure (NYHA II–III) with elevated PADd at rest (≥15 mm Hg). The data were obtained in a bioavailability study of two sprays of glyceryl trinitrate, which differed in their galenical characteristics and in the dose of GTN (0.4 mg vs. 0.8 mg). Following sublingual administration of each spray, PAPd, a/b-ratio and the plasma concentrations of GTN and its metabolites were measured up to 30 min. The relative bioavailability of GTN of the test preparation was estimated to be 157%, 161% and 147%, when calculated from the plasma concentration-time data or the integrated effect of GTN on a/b-ratio or PAPd, respectively. The mean time courses of the decrease in PAPd and the increase in the a/b-ratio of the finger pulse curve were mirror images. Thus, there was a strong correlation between the mean values of PAPd and a/b-ratio following the administration of glyceryl trinitrate. Since the slope of the relationship differed considerably between the patients, the magnitude of effect of GTN on PAPd in the individual patient could not be predicted from the changes in a/b-ratio.
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  • 64
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    European journal of clinical pharmacology 44 (1993), S. 463-466 
    ISSN: 1432-1041
    Keywords: Benazepril ; Proteinuria ; benazeprilat ; ACE inhibitor ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have investigated whether the pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril hydrochloride are altered with proteinuria by studying 8 patients with major proteinuria of different causes who were given a single dose of 10 mg p.o. The maximum plasma concentration of benazepril was found between 0.5 and 2 h after dosing (median 1 h). Its elimination was almost complete within 6 h. Peak plasma levels of benazeprilat, the active metabolite of benazepril, were observed between 1 and 6 h (median 2.5 h). The elimination of benazeprilat from plasma was biphasic, with mean initial and terminal half-lives of 3.0 and 17.3 h, respectively. On average, the pharmacokinetic parameters of benazepril and benazeprilat in the patients did not differ from those in a historical control group of healthy volunteers, but intersubject variability in the AUC and half-lives of benazeprilat was greater in the patients. Plasma ACE was completely inhibited from 1.5 to 6 h after dosing, and at 48 h the mean inhibition was still 42 %. Plasma renin showed substantial intersubject variation. Mean supine blood pressure (systolic/diastolic) was reduced from baseline by a maximum of 18/13 mm Hg at 6 h. Proteinuria was diminished after benazepril in 7 patients. In conclusion, the results of this study suggest that proteinuria in the nephrotic range does not require a change in benazepril dosage.
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  • 65
    ISSN: 1432-1041
    Keywords: dDAVP ; bioavailability ; gastrointestinal tract ; healthy volunteers ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP) from different regions of the gastrointestinal (GI) tract (stomach, duodenum, jejunum, ileum, colon, rectum) has been studied in 6 healthy, male volunteers aged 24 to 35 years, followed for 12 h after each drug administration. For i. v. administration the subjects received 4 μg dDAVP. For intestinal administration 400 μg dDAVP was directly applied to six distinct sites in the GI tract via two or four channel tubes with or without a distal occlusive balloon. Biological effects were assessed and plasma and urinary levels of dDAVP were measured using a specific, sensitive RIA. Urine osmolality remained elevated and diuresis decreased for 12 h following dDAVP administration irrespective of the site of application. After i. v. administration, the half-life of elimination of dDAVP was 60.0 min, plasma clearance 1.7 ml·min−1·kg−1, amount excreted in urine 2.0 μg and renal clearance was 0.8 ml·min−1·kg−1. The mean bioavailability (f) after gastric application was 0.19% (range 0.02–0.35%). f was 0.24% after duodenal application (range 0.04–0.62%), 0.19% after jejunal (range 0.01–0.41%), 0.03% after distal ileal (range 0.01–0.08%), 0.04% after proximal colonic (range 0.01–0.12%) and 0.04% after rectal (0.01–0.10%) application. The bioavailability was significantly higher in the three upper GI regions in comparison to the three lower regions. The bioavailability of dDAVP after gastric, duodenal and jejunal application was similar to that after swallowing a tablet in a previous study. Absorption from the ileum was lower than expected and no preferential site of absorption was found.
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  • 66
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    European journal of clinical pharmacology 42 (1992), S. 171-174 
    ISSN: 1432-1041
    Keywords: Quinine ; Malaria ; pharmacokinetics ; red blood cells ; plasma ; saliva ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quinine has been studied in ten healthy adult Africans after intravenous infusion and oral ingestion of a 500 mg dose. Blood and saliva samples were collected over 48 h and quinine in plasma, red cells and saliva was determined by HPLC. Quinine was rapidly and almost completely absorbed after an oral dose, with absorption half-life of 0.53 h, a tmax of 1–3 h and a bioavailability of 88%. Analysis of the i. v. data gave an apparent volume of distribution of 3.6 1·kg−1 and a plasma clearance of 0.19 l·kg−1·h−1. The concentration-time curves for plasma, red cells and saliva had declining phases were approximately parallel, giving a similar half-life that in all three media. The half-lives after the i. v. infusion also did not different from those after oral administration. The dose was well tolerated by both methods of administration.
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  • 67
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    European journal of clinical pharmacology 42 (1992), S. 175-179 
    ISSN: 1432-1041
    Keywords: 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) ; Triflusal ; triflusal metabolite (HTB) ; pharmacokinetics ; protein binding ; ultrafiltration ; binding constant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) is the main active metabolite of the platelet anti-aggregant drug triflusal. Its binding to plasma proteins of rats and healthy volunteers in vitro and in vivo has been studied. Rats were given a single oral dose of 50 mg·kg−1 triflusal and the healthy volunteers received 300 mg as a single oral dose or a multiple dose regimen of 600 mg every 24 h and 300 mg every 8 h, both for 13 days. Protein-free HTB was obtained by ultrafiltration. Unbound and total HTB concentrations were determined by HPLC. HTB was primarily bound to albumin in plasma. The Scatchard plots suggested two types of binding sites for HTB on the albumin molecule. In rats, the binding constants (K=intrinsic affinity constant, n=number of binding sites) were K1=1.4×105 l·mol−1, n1=1.23, and K2=4.1×103 l·mol−1 and n2=3.77. The mean plasma concentration in rats after oral administration was 185 (37) μg·ml−1 (protein-free HTB: 2.44 (0.77)%). The binding constants in human plasma were K1=4.7×105 l·mol−1, n1=1.93, K2=4.3 l·mol−1 and n2=4.28. The plasma HTB concentration in man (n=8) was 35 μg·ml−1 (Cmax) after a single oral dose of triflusal 300 mg, 172.96 μg·ml−1 (Cmax·ss) during the multiple dosage regimen of 300 mg every 8 h, and 131 μg·ml−1 (Cmax·ss) during the multiple oral dose regimen of 600 mg every 24 h. Unbound HTB ranged from 0.27 to 0.43%, depending on dose. HTB had high affinity for plasma albumin, which was not saturable after therapeutic doses. It showed linear elimination.
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  • 68
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    European journal of clinical pharmacology 42 (1992), S. 181-185 
    ISSN: 1432-1041
    Keywords: Glycerol ; brain oedema ; serum ; cerebrospinal fluid ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Glycerol 50 g infused i. v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom was given 500 ml of a 10% solution IV over 4 h, serum and CSF were repeatedly sampled during and after the infusion and glycerol was measured enzymatically. The highest serum glycerol level of 191–923 mg/l was observed at the end of the infusion. The maximum CSF glycerol of 18.7–110.8 mg/l was attained 0–1 h after the end of the infusion. Elimination both from serum and CSF approximated a single-exponential decay; the elimination half-life from serum was 0.29–0.56 h compared to 1.03–3.68 h from CSF. In six of the seven cases there was a temporary reversal of the serum/CSF concentration gradient during glycerol elimination. The ratios of the AUCs of CSF and serum, which describe the overall penetration of glycerol into CSF, ranged from 0.09–0.31. In conclusion, the serum level of glycerol produced by giving 50 g IV glycerol over 4 h may not be sufficiently high reliably dehydrate to brain tissue in many patients, and the slow elimination of glycerol from the CSF may be related to the so-called rebound phenomenon.
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  • 69
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    European journal of clinical pharmacology 42 (1992), S. 187-191 
    ISSN: 1432-1041
    Keywords: Dipyrone ; Acetylation phenotype ; metabolism ; pharmacokinetics ; urinary excretion ; metabolite clearance
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The formation and urinary excretion of the dipyrone metabolites, methylaminoantipyrine (MAA), aminoantipyrine (AA), formylaminoantipyrine (FAA) and acetylaminoantipyrine (AAA) were determined following administration of a single oral 1.0 g dose of dipyrone to 12 healthy volunteers. The AAA/AA plasma ratio showed that 3 subjects were slow and 9 were rapid acetylators. Pharmacokinetic parameters were determined separately for each group. A good correlation was found between the plasma and urine AAA/AA ratios. The renal clearance of the four metabolites was similar for both phenotypes. A significant difference in the rate of formation of dipyrone metabolites was found for AA, 0.25 (slow) vs 0.1 ml·min−1·kg−1 (rapid), and for AAA 0.75 (slow) vs 7.53 ml·min−1·kg−1 (rapid). There were comparable differences between slow and rapid acetylators in the AUC and the urinary excretion extrapolated to infinity for AA and AAA. The present results show that the kinetics of dipyrone metabolites in plasma and urine can provide a useful measure of the activity of the enzymes involved in their production.
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  • 70
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    European journal of clinical pharmacology 42 (1992), S. 197-201 
    ISSN: 1432-1041
    Keywords: Digoxin ; Salbutamol ; serum ; skeletal muscle digoxin ; pharmacokinetics ; drug interaction ; serum potassium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of the β2-adrenoceptor agonist salbutamol has previously been shown to decrease serum digoxin concentration in healthy volunteers. A possible explanation of the phenomenon is a β2-adrenoceptor-mediated increase in the specific binding of digoxin to skeletal muscle. The present study was undertaken to further elucidate the effect of salbutamol on the pharmacokinetics of digoxin in man. Nine volunteers were studied on two occasions during salbutamol or placebo treatment. On test days salbutamol, 4 μg·kg−1·h−1 or saline was infused for 10 h, preceded and followed by four and three days, respectively, of oral administration. A single i. v. injection of digoxin 15 μg·kg−1, was given 20 min after starting the infusion. At the end of the infusion a muscle biopsy was taken from the vastus lateralis. Blood samples for the analysis of serum digoxin and potassium were repeatedly taken over 72 h. Urine was collected over a period of 24 h for determination of the renal excretion of digoxin and potassium. The serum digoxin concentration, expressed as the AUC 0–6 h was 15% lower during salbutamol infusion than during saline infusion. Salbutamol caused significantly faster elimination of digoxin from the central volume of distribution to deeper compartments. Salbutamol had no effect on the renal clearance of digoxin. The skeletal muscle digoxin concentration tended to be higher (48%) during salbutamol compared to placebo treatment. The serum potassium concentration was significantly lower after salbutamol compared to placebo, as was the rate of renal excretion of potassium. The results support the hypothesis that the salbutamol-induced decrease in serum digoxin is caused by increased distribution of digoxin to skeletal muscle (and possibly other tissues), and that this may be secondary to a β2-adrenoceptor-mediated increase in Na-K-ATPase activity.
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  • 71
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    European journal of clinical pharmacology 42 (1992), S. 203-207 
    ISSN: 1432-1041
    Keywords: Nicorandil ; pharmacokinetics ; angina pectoris ; uraemia ; adverse effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of oral nicorandil 20 mg 12 hourly for 9 doses was evaluated in 21 hospitalized patients with angina pectoris due to coronary heart disease and with normal and impaired renal function. Patients were divided into 3 groups based on creatinine clearance (CLCr): GROUP I (n=6) 〉 80 ml/min, GROUP II (n=8) 20–80 ml/min, and GROUP III (n=7) 〈 20 ml/min. After the first dose, the total clearance of nicorandil (CL) value did not change with increasing renal failure and so was not dependent on creatinine clearance. After the last dose CL was 51 l·h−1 in Group I, 44 l·h−1 in Group II and 56 l·h−1 in Group III, and it was not related to creatinine clearance. The percentage of the dose excreted in the urine was 0.4%. No significant difference was noted in any of the other pharmacokinetic parameters examined in the three groups, not even on comparing values obtained on the first and last days of treatment. The findings suggest that there is no need to change the dose of nicorandil in subjects with different degrees of renal failure.
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  • 72
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    European journal of clinical pharmacology 46 (1994), S. 83-85 
    ISSN: 1432-1041
    Keywords: Enuresis ; Oxybutynine chloride ; children ; pharmacokinetics ; adverse effects ; anticholinergic actions
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Anticholinergic adverse-effects in children treated with conventional doses of oxybutynine led us to measure plasma oxybutynine levels in children. 18 children, aged 5 to 13 y, who required treatment with oxybutynine chloride for daytime incontinence were studied. Plasma concentrations were measured on the fifth day of a course of treatment in which the dose was adapted to the child's body weight; the dose was given twice daily at 12-hour intervals. In 10 children aged between 5 and 8 y, the mean dose was 0.1 mg · kg−1. In 8 children aged between 10 and 13 years, the mean dose was 0.15 mg · kg−1. The highest concentration was usually found between 1 and 2 h after administration. The subsequent fall in concentration was rapid and after 6 h oxybutynine was no longer measurable in 14 of the children. The concentrations found were not different from those seen in adults given equivalent doses. The results show that plasma concentrations in children were not very different from those observed in adults if the dose were adapted to the body weight of the children. No special differences in paediatric use were revealed that might explain the particular adverse-effects. The results of the study argue against the dosage regimen proposed before these adverse events were detected. They strongly favour a dose adapted to the body weight of the child, with a 12-hour interval between doses.
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  • 73
    ISSN: 1432-1041
    Keywords: Steroid 5α-reductase inhibitor ; Testosterone metabolism ; MK-0434 ; pharmacodynamics ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A four-period, two-panel, single-rising-dose study (0.1–100 mg) was conducted in healthy males to investigate the pharmacodynamics, tolerability and pharmacokinetics of MK-0434, a steroid 5α-reductase inhibitor. MK-0434 was associated with a significant reduction in dihydrotestosterone, which was maximal at 24 h and maintained through 48 h post treatment. The maximum reduction was approximately 50 % and occurred at all doses above 5 mg (10, 25, 50 and 100 mg). MK-0434 appeared to have no effect on serum testosterone at these single doses. Rising single doses of MK-0434 were associated with an increase in Cmax and AUC but the changes were less than proportional to dose, most likely due to nonlinear absorption. MK-0434 given in single doses up to 100 mg was without significant adverse effects in healthy male volunteers. In summary, MK-0434 is a well-tolerated, potent, orally active 5α-reductase inhibitor in man.
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  • 74
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    European journal of clinical pharmacology 46 (1994), S. 261-265 
    ISSN: 1432-1041
    Keywords: Cystic fibrosis ; Cyclosporin ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Cyclosporin (CsA) is currently the main immunosuppressive agent used in organ transplantation with considerable improvement in graft survival. Oral CsA solution is highly lipophilic, and its bioavailability may be reduced in cystic fibrosis (CF) heart-lung transplant recipients with pancreatic, gastrointestinal, and hepatic insufficiency. The bioavailability of oral CsA solution in 7 CF transplant recipients (5 male and 2 female with a mean age of 27 years and a mean weight of 49 kg) and 3 non-CF heart-lung recipients (1 male and 2 female with a mean age of 41 years and a mean weight of 60 kg) was studied. Following intravenous CsA administration, the kinetic curves were similar with no significant difference in the volume of distribution and clearance of CsA demonstrated between the CF and non-CF groups. The mean daily dose of oral CsA in 7 CF subjects (23.3 mg·kg−1) was significantly higher than the 3 non-CF heart-lung recipients (4.8 mg·kg−1). The mean maximum blood concentration of CsA for the oral dose was 776 ng·ml−1 for the 7 CF subjects, which was comparable with the mean peak values of 789 ng·ml−1 for the 3 non-CF control subjects. Poor enteral absorption of CsA probably accounts for the significantly lower mean bioavailability in the 7 CF subjects (14.9%) compared with the 3 non-CF control subjects (39.4%). The effects on the bioavailability of oral CsA solution by pancreatic enzymes (Creon) and histamine-2 antagonist (ranitidine) were also evaluated in the 7 CF subjects. No significant difference was demonstrated.
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    European journal of clinical pharmacology 44 (1993), S. 247-251 
    ISSN: 1432-1041
    Keywords: Proguanil ; Pregnancy ; Malaria ; cycloguanil ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and whole blood concentrations of proguanil, its active metabolite cycloguanil, and the inactive metabolite 4-chlorophenyl-biguanide, were measured by HPLC in 10 healthy Karen women in the last trimester of pregnancy, following a 200 mg single oral dose of proguanil. Four of these women were restudied 2 months after delivery. The pharmacokinetic properties of proguanil were similar during and after pregnancy. Median peak plasma concentrations of proguanil during pregnancy and following delivery were 212 and 215 ng·ml−1, and occurred at 4.5 and 5 h, respectively. Mean plasma AUC values for proguanil during and following pregnancy were 94 and 98 ng·h·ml−1·kg−1, respectively. Corresponding whole blood AUC values were 361 and 396 ng·h·ml−1·kg−1. The mean elimination half lives and mean residence times of proguanil in plasma and whole blood were 12.3 and 19.6 h and 13.8 and 20.7 h respectively during pregnancy. Following pregnancy these values were 17.1 and 19.7 h for plasma and 19.7 h and 20.2 h for whole blood respectively. Mean peak plasma and whole blood concentrations of cycloguanil following pregnancy were 25 and 22 ng·ml−1 respectively. During pregnancy peak cycloguanil concentrations in both plasma and whole blood were markedly lower, 13 and 12 ng ml−1, respectively. Two pregnant women (neither of whom were restudied) were probably poor metabolisers of proguanil. The mean ratio of proguanil to cycloguanil plasma AUC was 16.7 in the third trimester of pregnancy and 7.8 following pregnancy, compared with less than 5 in previously reported studies. The concentrations of 4-chlorophenylbiguanide in both plasma and whole blood in pregnant subjects were also lower than those after pregnancy. These data show that blood concentrations of the active antimalarial metabolite cycloguanil are reduced in late pregnancy and that the currently recommended dose of proguanil could be inadequate for antimalarial prophylaxis in pregnant women.
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  • 76
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    European journal of clinical pharmacology 44 (1993), S. 265-269 
    ISSN: 1432-1041
    Keywords: Cyclosporine ; Renal transplantation ; pharmacokinetics ; intraindividual variation ; circadian variation
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The intraindividual variability and circadian variation of oral cyclosporine (CsA) pharmacokinetics were studied over 24 h in 18 renal transplant recipients at steady state, and in 10 of the patients during a second 24 h period. The absolute percentage intraindividual difference in daytime AUC (0–12 h) ranged from 2% to 54% (mean 30%), and the corresponding variability in nighttime AUC (0–12 h) ranged from 5% to 80% (mean 34%). The pharmacokinetic variables t1/2, tmax and Cmax were more variable than the AUC (0–12 h) both during the day and at night. The evening trough level was significantly lower than the morning trough level; 185 ng · ml−1 versus 223 ng · ml−1. This, together with a significantly longer t1/2 in the night than the day, suggested circadian variability in the pharmacokinetics of CsA. In a separate retrospective study in 162 renal transplant recipients given CsA by constant intravenous infusion, repeated CsA blood concentration measurements at steady state showed lower concentrations during the day than the night, suggesting higher CsA clearance during daytime. It is concluded that CsA pharmacokinetics in renal transplant recipients, besides the well-known interindividual variability, also displays large intraindividual variability as well as circadian variation. Our findings further emphasize the necessity and difficulty of pharmacological monitoring in the clinical use of CsA in organ transplantation.
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  • 77
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    European journal of clinical pharmacology 44 (1993), S. 301-302 
    ISSN: 1432-1041
    Keywords: Adriamycin ; Haemodialysis ; adriamycinol ; pharmacokinetics ; moment analysis
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  • 78
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    European journal of clinical pharmacology 44 (1993), S. 305-306 
    ISSN: 1432-1041
    Keywords: Atenolol ; bioavailability ; intestinal absorption ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We investigated the dose proportionality after the intake of oral atenolol 25, 50, 100 and 150 mg. Standard tablets were taken by 8 healthy volunteers in randomised order of doses. The area under the curve divided by dose did not differ between the doses, indicating that the absorption of this hydrophilic compound, with known incomplete bioavailability, was constant over the range tested.
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  • 79
    ISSN: 1432-1041
    Keywords: Esmolol ; β1-Adrenoceptor antagonist ; tricresylphosphate ; pharmacokinetics ; effect kinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of esmolol at different rates of infusion (100, 250 and 500 μg·kg−1 BW·min−1) were compared with β-adrenoceptor occupancy (β1 and β2, estimated by a subtype selective radioreceptor assay) and plasma concentrations of esmolol and its acid metabolite were measured by HPLC. Up to a rate of infusion of esmolol of 500 μg·kg−1 BW·min−1 there was a maximal β1-receptor occupancy of 84.7% while β2-receptor occupancy was below the detection limit; confirming the β1 selectivity of esmolol. Exercise-induced increases in heart rate and systolic blood pressure were reduced by esmolol in a dose-dependent manner. The estimated EC50 values of rate of infusion for the reduction in heart rate and systolic blood pressure during exercise were 113 and 134 μg·kg−1 BW · min−1, respectively. Additionally, heart rate and systolic blood pressure were reduced moderately at rest. Because of the short elimination half-life of esmolol caused by the rapid hydrolysis to its acid metabolite, 45 min after end of infusion high plasma concentrations of the metabolite (maximally 80 μg·ml−1) but no esmolol were detectable. Since no in vivo effects have been observed, despite the presence of high plasma concentrations of the metabolite, the metabolite did not participate in the observed effects up to an infusion rate of esmolol of 500 μg·kg−1 BW·min−1. The plasma concentrations of antagonist detected by radioreceptor assay and plasma concentrations of esmolol detected by HPLC showed a good correlation (r=0.97). Since the cardiovascular effects, determined before and 45 min after termination of infusion of esmolol were similar, it can be concluded that the observed effects on heart rate and systolic blood pressure are exclusively mediated by esmolol.
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  • 80
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    European journal of clinical pharmacology 49 (1996), S. 387-391 
    ISSN: 1432-1041
    Keywords: Key words Liver function tests; elderly ; pharmacokinetics ; geriatrics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66–92 y) and 12 healthy volunteers (20–35 y). Methods: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). Results: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 μmol*h⋅l−1, clearance was reduced (5.0 vs. 11.8 l⋅h−1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P 〈 0.0001). Conclusion: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
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  • 81
    ISSN: 1432-1041
    Keywords: Ramipril ; Piretanide ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers. The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0–4 h) and ramiprilat (0–24 h) (from 15.8 to 19.8 ng·ml−1·h, and from 63.4 to 74.6 ng·ml−1·h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73 % of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide. The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril. Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers.
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  • 82
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    European journal of clinical pharmacology 46 (1994), S. 573-574 
    ISSN: 1432-1041
    Keywords: Standard deviation ; Arithmetic mean ; pharmacokinetics
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  • 83
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    European journal of clinical pharmacology 46 (1994), S. 565-567 
    ISSN: 1432-1041
    Keywords: Phenytoin ; Saliva ; therapeutic drug monitoring ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of atropine-induced reductions in saliva flow rate on saliva phenytoin concentrations were evaluated in a randomised placebo-controlled crossover study in a group of epileptic patients stabilised on the drug. Pretreatment with atropine caused significant reductions in saliva flow rates during the first 4 h, compared to saline. The AUC0–4 h for saliva flow rate was significantly reduced by atropine (245 g vs 327 g) and the saliva phenytoin AUC0–4 h was significantly increased (5.6 μg · ml−1 · h vs 4.5 μg · ml−1 · h) without affecting plasma phenytoin concentrations. The saliva/plasma phenytoin AUC0–4 h ratio was therefore significantly increased by atropine (0.15 vs 0.12). However, there was a poor correlation between saliva/plasma phenytoin concentration ratios and saliva flow rates for the two treatments in the individual patients (correlation coefficient ranged from 0.25 to 0.65). These findings demonstrate that saliva phenytoin concentrations are increased by reductions in saliva flow rate. Caution is therefore required when saliva phenytoin concentrations are used for therapeutic monitoring in the presence of factors which may affect saliva flow rate.
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  • 84
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    European journal of clinical pharmacology 47 (1994), S. 61-65 
    ISSN: 1432-1041
    Keywords: Cyclosporine A ; kidney transplant ; nephrotic syndrome ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetic parameters of cyclosporine (CsA) were determined in 23 kidney transplant recipients and 19 children with nephrotic syndrome, after intravenous and oral administration. The mean bioavailability was 39 %, blood clearance was 0.55 l · h-1 · kg-1 and volume of distribution at steady-stade was 2.77 l · kg-1. The absorption profile was monophasic (67 %), biphasic (29 %) or poor (4 %). The maximum blood concentration of CsA was significantly higher in children with a monophasic profile than in children with a biphasic profile (550 vs 380 ng · ml-1). Blood clearance was significantly higher in the transplant recipients than in the patients with nephrotic syndrome (0.65 vs 0.43 l · h-1 · kg-1. Although age, haematocrit, creatinine clearance, serum albumin and cholesterol differed between the two groups, only haematocrit and creatinine clearance were significantly (negatively) correlated with CsA clearance.
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  • 85
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    European journal of clinical pharmacology 47 (1994), S. 81-84 
    ISSN: 1432-1041
    Keywords: Dihydrotachysterol ; bioavailability ; pharmacokinetics ; human ; HPLC
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability of four preparations containing dihydrotachysterol (DHT2) was tested in two separate trials with administration of single, oral doses of 1 mg per individual. The relative bioavailability of corresponding preparations (capsules vs capsules and oral solution vs oral solution) was tested in a randomised, crossover pattern within the same group of volunteers. Two different groups of 24 healthy volunteers took part in each trial. Solution and capsule bioavailability was also compared inter-individually. A new sensitive HPLC-method (quantification limit 0.5 ng · ml-1) was used for the measurement of DHT2 concentration in serum. Three of the preparations tested had a similar bioavailability (mean AUC values of 195.5–223 ng · h · ml-1); the bioavailability of the fourth preparation (A.T.10 oral solution) was considerably lower (mean AUC value 111.5 ng · h · ml-1). The present dosage recommendations of all four preparations are identical. A new dosage recommendation is thus required for the oral solution with low bioavailability (A.T.10).
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  • 86
    ISSN: 1432-1041
    Keywords: Doxycycline ; bioavailability ; pH dependent absorption ; pharmacokinetics ; carrageenate ; adverse events
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of increased gastric pH (obtained by pre-treatment with omeprazole) on the bioavailability of doxycycline monohydrate and doxycycline carrageenate has been investigated in 24 healthy volunteers, using an open, randomised, four-treatment, four-period, crossover, 2×2 factorial design. Each subject received a single dose of 100 mg of each of the doxycycline formulations with and without pre-treatment with omeprazole (40 mg daily for 7 days). The two formulations were bioequivalent (rate and extent) during fasting without omeprazole pre-treatment, whereas after omeprazole, the monohydrate showed a highly significant decrease in bioavailability (38% for AUC and 45% for Cmax) compared to the carrageenate formulation, which was not affected by prior administration of omeprazole. Many of the subjects did not reach a therapeutic plasma level of doxycycline during the combination of omeprazole and doxycycline monohydrate, and most adverse events (mainly gastrointestinal) were reported after this combination. As large populations of patients have a high gastric pH due to frequent use of H2-blockers, proton pump inhibitors and antacids, as well as to physiological achlorhydria, the decreased absorption of doxycycline monohydrate may well have a clinical impact, for example when the patients are treated with tetracyclines for an infection.
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  • 87
    ISSN: 1432-1041
    Keywords: Medifoxamine ; pharmacokinetics ; pharmacodynamics ; elderly volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and psychomotor effects of medifoxamine, a 5 HT reuptake inhibitory antidepressant, were studied in healthy elderly volunteers after single and multiple dosing. The elimination half life (t1/2z) after single doses of 300 mg was 2.8 h — almost identical to that found in young volunteers. After seven days of dosing at 100 mg three times daily the mean corrected AUC after 300 mg significantly increased from 1.04 to 1.34 mg.h.l−1 and t1/2z increased to 4.0 h (NS). There were no significant changes in critical flicker fusion frequency, symbol digit substitution, continuous attention or choice reaction times.
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  • 88
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    European journal of clinical pharmacology 46 (1994), S. 179-180 
    ISSN: 1432-1041
    Keywords: Teicoplanin ; haemodialysis ; renal failure ; pharmacokinetics
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  • 89
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    European journal of clinical pharmacology 46 (1994), S. 237-242 
    ISSN: 1432-1041
    Keywords: Metoprolol ; bioavailability ; bioequivalence ; receptor binding assay ; pharmacokinetics ; sustained release formulation
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability and pharmacodynamic bioequivalence of a conventional and an experimental sustained-release formulation of 100 mg metoprolol tartrate were studied in a randomised cross-over study in seven healthy volunteers by assessing over 24 h the plasma kinetics of R,S-metoprolol, its β1-adrenoceptor binding component, and by determining the extent to which the active drug moiety in plasma occupied rabbit lung β1-and rat reticulocyte β2-adrenoceptors. The formulations differed markedly in their kinetic characteristics: the peak plasma concentration (Cmax) of R,S-metoprolol after administration of the conventional formulation was 140 ng·ml−1, (n=7) and it was approximately one-third of that after the sustained-release formulation, 49 ng·ml−1, (n=6); the AUC0–24 h-values for the formulations were 700 and 310 ng·h·ml−1, respectively. The Cmax for the β1-adrenoceptor binding component of metoprolol was 180 ng·ml−1 (n=7) after administration of the conventional, and 74 ng·ml−1 after administration of the sustained-release formulation. The corresponding AUC0–24 h-values for the receptor binding component were 920 and 470 ng·h·ml−1 (n=7). Thus, the kinetic differences between R,S-metoprolol and the β1-receptor binding component were considerable and they were affected by the type of formulation. In general, after administration of the sustained-release formulation, the percentage β1- and β2-adrenoceptor occupancy of metoprolol in plasma was 5–15% less than after administration of the conventional formulation. At 0.5–1.5 h after drug intake the average β1-adrenoceptor occupancy of the conventional formulation varied between 80–90% and that of the sustained release formulation between 20–76%. At these times the differences in receptor occupancy were significant; at 0.5–2 h after drug intake the average β2-adrenoceptor occupancy of the conventional formulation varied from 20–30%, and that of the sustained-release formulation was 2–17%. At other times the difference in receptor occupancy between the formulations was not significant. The results demonstrate that plasma concentration-kinetics were more discriminating than β-adrenoceptor-binding in analysing bioequivalence. It was possible to determine the bioavailability of the active ingredient of metoprolol and to study pharmacodynamic bioequivalence by using receptor binding assays.
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  • 90
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    European journal of clinical pharmacology 47 (1995), S. 507-511 
    ISSN: 1432-1041
    Keywords: Methotrexate ; Juvenile rheumatoid arthritis ; pharmacokinetics ; age dependence
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Children with juvenile rheumatoid arthritis (JRA) have been reported to require higher doses (per kg body weight) of methotrexate (MTX) than adults with rheumatoid arthritis to control their disease. The purpose of the present study was to characterise the plasma pharmacokinetics of MTX and its major metabolite, 7-hydroxymethotrexate (7-OHMTX) in children, and to compare the results with those previously obtained in adults. Thirteen patients (age 5–16 y) with JRA (median disease duration 5.5 y) were studied after once weekly oral administration of MTX (median 0.21 mg·kg−1). The analytical method was sufficiently sensitive to permit determination of plasma and urinary concentrations of MTX and 7-OHMTX during the entire dose interval in most of the patients. The dose normalized area under the plasma concentration versus time-curve (AUC) of MTX increased with the age of the children and was lower than previously found in adults. The dose normalized AUC of 7-OHMTX was not dependent on age. No correlation was found between the AUCs of MTX and 7-OHMTX. The results suggest that the age-dependence of the pharmacokinetics of MTX might explain the observation that at least some children require higher doses of MTX than adults to obtain a sufficient therapeutic effect.
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  • 91
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    European journal of clinical pharmacology 47 (1995), S. 525-530 
    ISSN: 1432-1041
    Keywords: Antipyrine disposition ; Obesity ; pharmacokinetics ; oxidative metabolism ; weight reduction
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Following an overnight fast and 2 days of abstention from caffeine, a single 1.0-g oral dose of antipyrine was administered to 20 obese but otherwise healthy subjects (group A) and 11 healthy volunteers (group B). Weight, Body Mass Index (BMI) and % of Ideal Body Weight (IBW) were significantly greater in the obese than in the lean group. (Mean 110.4 vs 62.7 kg; 38.5 vs 22.3 kg · m−2 and 181vs 106 % respectively). In a subgroup of 6 obese subjects (group C) antipyrine was given again 11.3 months later after a 29.8 kg mean weight loss. Antipyrine apparent volume of distribution (V) and elimination half-life (t 1/2) were significantly greater in the obese than in the lean group (V 49.9 vs 34.3 l respectively; t 1/2 15.5 vs 12.0 h respectively), but its clearance rate (CLo) values were similar. V corrected for total body weight was significantly reduced in group A than in group B (0.45 vs 0.55 l · kg−1 respectively). Stratified comparison of antipyrine pharmacokinetics between obese and lean subjects according to age, gender and smoking habits did not alter the overall results. In group C, weight reduction was associated with a significant decrease in antipyrine V (from 51.8 to 47.5 l) and t 1/2 (from 15.1 to 12.7 h), and a non-significant increase in antipyrine CLo. We conclude that in severely obese subjects, antipyrine total V is mildly increased but V corrected for total body weight is significantly decreased. In addition, obesity is associated with a slight prolongation of antipyrine t 1/2 whereas its CLo is unaltered. These findings may indicate that obesity, even in its extreme form, has a negligible effect on the oxidative metabolic capacity of the liver.
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  • 92
    ISSN: 1432-1041
    Keywords: Piroxicam ; β-Cyclodextrin ; pharmacokinetics ; healthy volunteers ; multiple dose ; adverse event
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract CHF1194 is an inclusion complex of β-cyclodextrin with the nonsteroidal anti-inflammatory drug piroxicam. In man, β-cyclodextrin acts as a carrier of piroxicam. As the inclusion complex of piroxicam-β-cyclodextrin is wettable and more water soluble, the absorption rate of the drug is increased whilst its other pharmacokinetic characteristics remain unchanged. The aim of the present study in 12 healthy subjects was to compare the oral bioavailability of 20 mg piroxicam in a CHF1194 tablet and a plain piroxicam capsule after a single dose and after two weeks of once daily administration, and also to assess the plasma levels and urinary excretion of β-cyclodextrin after CHF1194 administration. The two treatments were administered in cross-over fashion, separated by a wash-out period of three weeks. Piroxicam, 5′-hydroxypiroxicam and β-cyclodextrin were monitored in plasma and urine for 120 h after the first and last doses. Clinical tolerance was excellent and no adverse event occurred during either phase of the study. The extent of absorption of piroxicam from the CHF1194 tablet after the single dose was equivalent to that after the plain piroxicam capsule, within confidence limits of less than 80–125%. After repeated dosing, CHF1194 yielded the same steady-state systemic concentrations of piroxicam and 5′-hydroxypiroxicam as the reference capsule, and similar excretion pattern of the metabolite. After both single and multiple dosing, piroxicam was absorbed more rapidly after CHF1194, an expected consequence of the complexation of piroxicam with β-cyclodextrin. This may be of therapeutic interest as it might accelerate the onset of pain relief. The pharmacokinetics of piroxicam was linear after the doses used here, suggesting that long term treatment with CHF1194 should not require any change in dosing regimen. Even after 14 days of repeated administration of CHF1194, β-cyclodextrin could not be detected in plasma or urine, suggesting that in man the unchanged oligosaccharide was absorbed to a very small extent.
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  • 93
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    European journal of clinical pharmacology 46 (1994), S. 575-575 
    ISSN: 1432-1041
    Keywords: Renal clearance ; pharmacokinetics
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  • 94
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    European journal of clinical pharmacology 47 (1994), S. 75-79 
    ISSN: 1432-1041
    Keywords: Diltiazem ; Angina pectoris ; controlled release formulation ; metoprolol ; bioavailability ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Diltiazem CR tablets 120 mg b.i.d. for 1 week were compared with plain tablets 60 mg q.i.d. in 13 healthy male volunteers in a study of pharmcokinetic variables. Their antianginal efficacy was also compared in 23 patients with stable angina pectoris who were already on metoprolol. Both studies were of randomised, cross over design, and the clinical study was double blind. The pharmacokinetic variables of the two formulations were very similar except for the longer tmax of 4.4 h for diltiazem CR in comparison to 2.9 h for the plain tablets. The mean relative bioavailability of diltiazem CR in comparison with plain tablets was 1.14. The clinical study showed that after four weeks on diltiazem CR 120 mg b.i.d. or diltiazem plain tablets 60 mg q.i.d. in addition to metoprolol, there were significant decreases in weekly anginal attacks from 11 to 5 attacks/week, the number of nitroglycerin tablets consumed from 6 to 3 tablets/week, and an increase in the maximum workload from 116 to 126 and 123 W for diltiazem CR and plain diltiazem tablets, respectively, as compared to placebo. Five of the patients were angina free during diltiazem treatment. No difference in antianginal efficacy between the two preparations was seen. It was concluded that CR 120 mg b.i.d. appears bioequivalent to plain diltiazem tablets 60 mg q.i.d.
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  • 95
    ISSN: 1432-1041
    Keywords: Oxcarbazepine ; 10,11-dihydro-10-hydroxy-carbamazepine ; renal impairment ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have studied the effect of renal impairment on the pharmacokinetics of oxcarbazepine, its active monohydroxy-metabolite (which predominates in plasma), their glucuronides, and the inactive dihydroxy-metabolite after a single oral dose of oxcarbazepine (300 mg). Six subjects with normal renal function and 20 patients with various degrees of renal impairment participated. The mean areas under the plasma concentration-time curves of oxcarbazepine and its monohydroxy-metabolite were 2–2.5-times higher in patients with severe renal impairment (CLCR〈10 ml·min−1) than in healthy subjects. The apparent elimination half-life of the monohydroxy-metabolite [19 (SD 3) h] in these patients was about twice that in healthy subjects. The effect of renal impairment on the plasma concentrations of glucuronides was more marked. The renal clearances of the unconjugated monohydroxy-metabolite and its glucuronides (the main compounds recovered in urine) correlated well with creatinine clearance. The maximum target dose in patients with slight renal impairment (CLCR〉30 ml·min−1) should not be changed. In patients with moderate renal impairment (CLCR10–30 ml·min−1) it should be reduced by 50%. In patients with severe renal impairment (CLCR〈10 ml·min−1), the glucuronides of oxcarbazepine and its monohydroxy-metabolite are likely to accumulate during repeated administration, and dosage adjustment of oxcarbazepine in these patients could not be proposed from this single administration study.
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  • 96
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    European journal of clinical pharmacology 48 (1995), S. 385-390 
    ISSN: 1432-1041
    Keywords: Furosemide ; Dialysis ; continuous ambulatory peritoneal ; drug disposition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Single doses of oral and intravenous furosemide were given to 8 healthy male volunteers (40 mg) and 11 patients with renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD) (80 mg). In the volunteers, absorption was variable. Only one half of the intravenous dose and one third of the oral dose was available for renal pharmacological action as judged by the urinary recovery. In the patients, absorption was also variable and was markedly delayed (t max 128 vs 90 min) but more complete (bioavailability 70.1 vs 53.6%). The differences between the two groups were not significant, however (95% C.I.: -90 to 30 and -40.4 to 7.5 respectively). The mean elimination half-life was significantly longer in the patients following both the oral (228 vs 65.1 min) and intravenous dose (195 vs 60.3 min). The total body clearance of furosemide in the volunteers was 138 ml·min−1 and this was much lower in the CAPD patients (61.9 ml·min−1) in whom the renal clearance was minimal. The peritoneal clearance of furosemide was negligible. Although there were trends indicating differences in absorption between the two groups, the significant differences in furosemide disposition observed in CAPD patients were due to renal failure.
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  • 97
    ISSN: 1432-1041
    Keywords: Caffeine ; Cardio-green ; Indocyanine Green ; altitude ; metabolism ; pharmacokinetics ; hypoxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of chronic exposure to high altitude on the pharmacokinetics of caffeine and cardiogreen (ICG) were examined in eight healthy males (23–35 y) at sea level (SEA) and following 16 days residence at 4300 m (ALT). ICG (0.5 mg · kg−1) was administered as an intravenous bolus and caffeine (4 mg · kg−1) in an orally ingested solution. The concentration of ICG, caffeine, and the primary metabolites of caffeine (MET) were determined in serial blood samples and their pharmacokinetics computed. In comparison to SEA, ALT resulted in a significant decrease in the caffeine half-life (t1/2, 4.7 vs 6.7 h) and area under the curve (2.5 vs 3.7 g · 1−1 · min−1), and increased clearance (117 vs 86 ml · min−1 · 70 kg−1). In ALT the area under the curve of ICG significantly decreased (85 vs 207 mg · 1−1 · min−1) and the volume of distribution and clearance increased (5.2 vs 2.41 and 532 vs 234 ml · min−1 respectively) compared to SEA. There was a significant increase in the AUC ratio of MET to caffeine indicating that either metabolite formation or elimination was increased in ALT. These results demonstrate that in humans, chronic exposure to 4300 m results in the modification of the pharmacokinetics of caffeine and ICG.
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  • 98
    ISSN: 1432-1041
    Keywords: Diltiazem ; sustained-release formulation ; pharmacokinetics ; bioavailability ; bioequivalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The usual dosage regimen of diltiazem (Tildiem) is 60 mg 3–4 times a day. A sustained-release formulation has been developed (Mono-Tildiem LP 300 mg) in order to allow a single daily administration. Two repeated dosing studies were performed in healthy volunteers. The absolute bioavailability of sustained-release diltiazem LP 300 mg was investigated using concomitant i.v. administration of 13C-labelled drug: absolute bioavailability of the “once a day” formulation was 35%. The second study compared sustained-release diltiazem LP 300 mg with the standard formulation of diltiazem. The results showed that the diltiazem plasma concentrations obtained after the LP formulation remained stable between 2 and 14 h after administration and were compatible with a once a day administration. Relative bioavailability of sustained-release diltiazem LP 300 mg was 79.3% compared with diltiazem. Therefore, a unitary dose of sustained-release diltiazem LP 300 mg was chosen as the dose equivalent to the daily dose administered with the standard diltiazem formulation.
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  • 99
    ISSN: 1432-1041
    Keywords: Diabetes ; Human insulin ; Lorazepam ; pharmacokinetics ; glucuronidation ; enterohepatic circulation ; animal insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics of lorazepam was examined in 10 male patients with insulin-dependent diabetes mellitus before and following treatment with neomycin and cholestyramine. Neomycin and cholestyramine were given in an attempt to block the enterohepatic circulation of lorazepam and so to permit an in vivo estimate of hepatic glucuronidation. The volume of distribution and clearance of free lorazepam in diabetic patients were not significantly different from the corresponding estimates in 14 normal controls. Neomycin and cholestyramine increased the clearance of lorazepam by 63% consistent with their effect in non-diabetic controls. However, patients on beef/pork insulin exhibited a greater than normal increase on this interupting regimen (125%), and had a significantly greater neomycin/cholestyramine cycling-interrupted clearance of lorazepam than either normal controls or patients on human insulin (15.4 vs. 6.96 and 7.87 ml·min−1·kg−1). The clearance was correlated positively and significantly with HbA1c and glycated proteins (fructosamine), but only in patients on human insulin. Thus, the pharmacokinetics of lorazepam was not altered in patients with insulin-dependent diabetes mellitus. However, it is possible that there are differences in the rate and extent of hepatic glucuronidation and enterohepatic circulation of lorazepam between patients treated with beef/pork and human insulins and between diabetics treated with beef/pork insulin and non-diabetic controls.
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 48 (1995), S. 273-277 
    ISSN: 1432-1041
    Keywords: Mesalamine ; 5-aminosalicylic acid ; controlled release capsules ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract One gram single dose of Pentasa controlled-release capsules was administered to 24 healthy volunteers under fasting condition. Mean plasma 5-aminosalicylic acid (5-ASA) and acetyl 5-ASA concentrations peaked at 0.53 μg · ml−1 and 1.33 μg · ml−1 from 3 to 4 hours following dosing, respectively. The half-lives of both compounds could not be determined as absorption of 5-ASA was continuous throughout the gastrointestinal tract. An average of 29.4% (CV: 27%) of the dose was excreted in the urine primarily as acetyl 5-ASA. Up to 91.1% of the dose was released from the capsules. Forty percent of the dose (CV: 40%) was eliminated in the feces, with 8.9% of the dose remained as formulation bounded 5-ASA, indicating that controlled-release capsules continue to release drug throughout the GI tract. 5-ASA contributed 46.7% of the salicylates eliminated in the feces and acetyl 5-ASA accounted for the balance. Controlled-release capsules produced three times more total salicylates and 10 times more total and free 5-ASA in the feces than did 5-ASA suspension. Thus, while lower systemic levels of salicylates were absorbed, greater therapeutic quantities of 5-ASA were available in the bowel.
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