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  • bioavailability  (130)
  • 42.60  (90)
  • phosphorus
  • Springer  (276)
  • Copernicus
  • 1980-1984  (276)
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  • Springer  (276)
  • Copernicus
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  • 1
    ISSN: 1432-0649
    Keywords: 32.80 ; 42.60 ; 6.30
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The velocity distribution of evaporated Zr atoms has been measured by means of laser-induced fluorescence using a cw dye laser by scanning the laser line across the Doppler-broadened absorption line profile of the atoms. It is shown that the experimental data can be explained on the basis of an excitation theory for a three-level system developed from basic principles. It was calculated that the probability for an atom to be in the excited state mainly depends on the radiation-power density of the laser and on the residence time of the atom in the exciting laser light. It was found that the laser frequency must be well stabilized in order to meet the assumptions in the excitation calculation. Otherwise deviations to the theoretical predictions appear in the experimental results due to the jitter of the dye laser.
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  • 2
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    Applied physics 35 (1984), S. 123-126 
    ISSN: 1432-0649
    Keywords: 42.50 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Spatial separation of wavelengths in a CO2-laser resonator helps to avoid competitions. We have achieved this by means of a nearly concentric resonator with a grating or prism in its center. Thus, we demonstrated independent multiline emission with a variety of output spectra. The temporal sequence of the lines was conveniently controlled by varying their losses.
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  • 3
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    Applied physics 33 (1984), S. 23-27 
    ISSN: 1432-0649
    Keywords: 42.55 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract For the first time stable cw output of a FIR-CO2 hybrid laser has been achieved at wavelengths shorter than 300 μm. Due to the saturable absorber characteristic of the FIR laser gas, cw or pulsed emission is observed on both, the CO2 and the FIR laser output, depending on the operating conditions. Results are reported on different resonant lines in CH3OH and the 67 μm Raman line in NH3. The good efficiency of this laser is also demonstrated by the excitation of two new emission lines in CH3OH, namely 49 and 56 μm, pumped by 9R(22) and 9R(24), respectively.
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  • 4
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    Applied physics 33 (1984), S. 57-61 
    ISSN: 1432-0649
    Keywords: 33 ; 42.60 ; 82.50
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A laser photodesorption microscope has been applied to obtain 4×103-fold images of rhodamine crystals on a tip with a diameter of 66μm. Peculiarities of the formation of these images have been studied with different values of electric field strength on the tip and laser pulse intensities.
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  • 5
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    Applied physics 33 (1984), S. 179-185 
    ISSN: 1432-0649
    Keywords: 06 ; 07.60 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We describe a study, performed using heterodyne techniques, of the frequency fluctuations of two completely independent ring dye lasers locked to independent reference cavities. Single laser linewidths of less than 750 Hz were achieved, the principal limitation being residual vibrations from the noisy laboratory environment. With future design and environmental improvements, ultranarrow linewidths are expected thus providing a useful tool for a great variety of high precision experiments.
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  • 6
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    Applied physics 33 (1984), S. 213-218 
    ISSN: 1432-0649
    Keywords: 35 ; 82.40 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract CARS spectra of NH3 and the free NH2-radical in the NH stretch region at 3334 and 3220 cm−1 have been obtained, respectively. The NH2 radicals were generated by laser photolysis of 0.5 mbar NH3 at 193 nm with an ArF-exciplex laser and detected by time resolved CARS spectroscopy.
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  • 7
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    Applied physics 34 (1984), S. 63-67 
    ISSN: 1432-0649
    Keywords: 06 ; 07.60 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract An infrared frequency measurement chain is reported, the simplicity of which allows phase-coherent frequency measurements up to 30 THz. Frequency measurement is demonstrated on the 10P(28) line of the Lamb-dip stabilized13CO2-laser.
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  • 8
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    Applied physics 34 (1984), S. 129-137 
    ISSN: 1432-0649
    Keywords: 33.50 ; 42.10 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A theoretical description of a three-pulse transient grating technique is given where the pump pulses form orientational gratings. Including energy relaxation and angular reorientation the temporal behavior of the diffraction efficiency and energy transmission is discussed with respect to the dependence on the corresponding rate constants and the results are compared with experimental data for Rh6G and RhB. The polarization plane of the pulse diffracted by the grating is found to be rotated in dependence on its initial polarization.
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  • 9
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    Applied physics 35 (1984), S. 163-166 
    ISSN: 1432-0649
    Keywords: 42.50 ; 42.55 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We present an analytical expression for the small-signal gain of a Free Electron Laser (FEL) in the presence of a Gaussian mode. To describe the electron beam evolution we use the one-dimensional (1-d) Vlasov equation. Our perturbation result, valid for small values of the parameterq (length of the undulatorL divided by the Rayleigh rangeZ R), can be extrapolated to values ofq≈4÷5.
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  • 10
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    Applied physics 33 (1984), S. 63-74 
    ISSN: 1432-0649
    Keywords: 42.60 ; 78.30 ; 78.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract This review covers the field of vapor-phase dye lasers (VPDL) with special emphasis on prospects of gas lasers with optical pumping. Some peculiarities of the gaseous active medium and a possibility to control its density near the critical point are discussed. High specific laser energies (∼0.3J/cm−3), low thresholds, and high efficiencies (20–40%) made it possible to construct a powerful tunable VPDL.
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  • 11
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    Applied physics 33 (1984), S. 103-113 
    ISSN: 1432-0649
    Keywords: 42.68 ; 42.80 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A long-path absorption procedure for the determination of tropospheric OH concentrations is described in detail. Initial measurements using this method were carried out in Frankfurt a. M. By including in the evaluation the visible radiation of a frequencydoubled dye laser used in the measurements, it was possible to mathematically reduce the signal fluctuations caused by the scattering and density fluctuations of tropospheric air. The resulting detection limit was 3×106 OH per cm3. SO2 concentrations which had to be simultaneously determined in order to eliminate an interference effect, could be detected in the range of 1–40 ppb on the absorption path.
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  • 12
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    Applied physics 33 (1984), S. 9-16 
    ISSN: 1432-0649
    Keywords: 42.60 ; 42.20 ; 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We derive the most general equations of motion for the electrons and the electromagnetic field in a free-electron laser including the effects of diffraction and pulse propagation. The field evolution is expressed in terms of the amplitudes and phases of a complete set of transverse modes. The analytic solution is given in the small-signal regime, where the theory is shown to be in excellent agreement with a recent experiment at Orsay.
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  • 13
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    Applied physics 33 (1984), S. 83-90 
    ISSN: 1432-0649
    Keywords: 82.50 ; 82.40 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Tritium isotope separation by CO2-laser induced multiphoton dissociation of CTF3 is investigated. For the optimization of the performance of this working substance, trifluoromethane, the conditions to yield high-selectivity at high-operating pressure and low-critical fluence for complete dissociation are studied using our deconvolution procedure. The irradiation conditions are varied over the following ranges; wavenumber: 1052–1087 cm−1, gas temperature: 25°C to −78°C, CHF3 pressure: 5–205 Torr. The selectivities exceeding 104 are observed for 85–205 Torr CHF3 at −78°C by the irradiation at 1057 cm−1.
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  • 14
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    Applied physics 34 (1984), S. 29-31 
    ISSN: 1432-0649
    Keywords: 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Directional and wavelength sweep of a pulse train from a distributed-feedback dye laser is studied and found not to be a thermal effect, rather a gain-induced one. The directional sweep can be used for single-pulse selection.
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  • 15
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    Applied physics 35 (1984), S. 71-75 
    ISSN: 1432-0649
    Keywords: 42.60 ; 42.55 ; 42.72
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A simple model of the energy transfer between a booster dye and the active dye in a flashlamp pumped planar waveguide dye laser is described. Analytical results are compared with experiments for several dyes in the 600–650 nm region. A twofold increase of laser output was found at a wavelength (630 nm) which is of particular interest for several applications.
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  • 16
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    Applied physics 35 (1984), S. 119-122 
    ISSN: 1432-0649
    Keywords: 42.72 ; 42.80 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The output of a CO2 laser, operating on theP I(18) transition of13C16O2 at 26941 GHz (11.128 μm) was phase-locked to a 5 MHz signal from a primary Cs frequency standard by means of a frequency chain having only CO2 lasers as infrared sources. Simultaneously, four other CO2 lasers in the chain were phase-locked to the 26941 GHz output. This provided CO2 laser frequencies at 26 450 305, 26 940 815, 28 694 625, 29 442 480, and 33 185 715 MHz having zero long-term-average frequency error relative to the Cs standard, and the ±10−13 (≃3 Hz) long-term absolute uncertainty of the standard.
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  • 17
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    Applied physics 33 (1984), S. 187-193 
    ISSN: 1432-0649
    Keywords: 42.50 ; 42.55 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract It is shown by numerical analysis based on Lamb's equations of motion, that standing-wave lasers with purely homogeneously broadened emission lines exhibit regular multimode oscillations. Specifically, modes lying far from the line centre are quenched due to mode competition, and the amplitudes of the oscillating modes approach steady-state values. The stabilization of the amplitudes is normally accompanied, or followed, by an evolution of the phases towards a phase-locked regime, where the relative phasesψ n = 2φ n −φ n + 1 −φ n − 1 [φ n phase in then th mode, defined by (6)] attain either the value 0 or ± π. The build-up times for the relative phases are found to vary over a wide range.
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  • 18
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    Applied physics 33 (1984), S. 219-223 
    ISSN: 1432-0649
    Keywords: 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We describe the generation of excimer-laser pulses of 〈10 ps pulse width and up to 40 mJ pulse energy at 248.5 nm and their use in the measurement of ps gain dynamics in a KrF amplifier. Small-signal gain of 〉2×104, saturation energy density of 2.0 mJ/cm2, and gain recovery time of 4 ns were measured. In contrast to XeCl* no short-gain rcovery time was found in KrF* and the stored inversion could be fully depleted bya single ps pulse.
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  • 19
    ISSN: 1432-0649
    Keywords: 42.68 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract An analysis of 532 nm lidar data is presented for the retrieval of vertical extinction profiles. The strong influence of the relative humidity on the extinction-to-backscatter ratio is parametrized for this purpose. A comparison is made between remotely sensed and locally measured extinction coefficients, using reference values in aircraft and at ground level.
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  • 20
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    Applied physics 34 (1984), S. 191-192 
    ISSN: 1432-0649
    Keywords: 42.55 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A pulsed xenon ion laser has been used to pump a rhodamine 6G dye laser utilizing a ring resonator. The dye laser has been passively mode-locked; a pulsewidth of 0.5 ps and a 50 kW peak power have been obtained.
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  • 21
    ISSN: 1432-0649
    Keywords: 42.80 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The values of the chopping disc slot and mark space widths relative to the radius of the Gaussian beam are found, which achieve optimum harmonic-like and efficient amplitude modulation of the cw laser beam. The simple approximation for the waveform of the modulated laser power valid for these optimum or near optimum values of the chopping disc parameters is presented.
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  • 22
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    Applied physics 33 (1984), S. 17-21 
    ISSN: 1432-0649
    Keywords: 52.00 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A comparison of the operating characteristics of the high-voltage regime of the discharge in a hollow-cathode tube, the hollow-canthode discharge (HCD) and the discharge to a plane cathode are presented. The disappearnce of the hollow-cathode effect and the transition to a high-voltage discharge after inserting several anode rods into the cathode cylinder is exhibited. The similarity between the operating characteristics of such a high-voltage discharge and of a plane cathode discharge is shown. The loss of ions at the anode rods, as well at insulators or floating conductors is believed to be the reason behind the increase of the operating voltage and the disappearance of HCD characteristics. Practical means of increasing the operating voltage are mentioned.
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  • 23
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    Applied physics 33 (1984), S. 75-77 
    ISSN: 1432-0649
    Keywords: 42.30 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We report upon some experiments done on a continuous-wave argon-ion laser which offers 300 W output power in the visible and 34 W in the ultraviolet region of the spectrum, limited by the degradation of the resonator mirrors. To avoid destruction of the outcoupling mirror, a folded three-mirror instead of a two-mirror cavity was tried, resulting in nearly the same output power.
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  • 24
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    Applied physics 33 (1984), S. 95-98 
    ISSN: 1432-0649
    Keywords: 42.60
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    Topics: Physics
    Notes: Abstract Generation of single dye laser pulses of 12 ps pulse width (FWHM) and 1.2 mJ pulse energy is described using only one XeCl-excimer laser as pump source. At 1 Hz pulse repetition rate the stability of amplitude and pulse width of these pulses is excellent.
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  • 25
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    Applied physics 35 (1984), S. 233-236 
    ISSN: 1432-0649
    Keywords: 42.60 ; 07.77 ; 34.50
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    Topics: Physics
    Notes: Abstract The effect of resonant laser-light upon a charge-exchange source of eV-range sodium atoms is to decrease the Na kinetic energy by about 2 eV. The mechanism probably involves a reduction of the space charge in the low-energy ion precursors. The reduction is caused by electrons created in collisional ionization of laser-excited atoms. This is related to the well-known optogalvanic effect. A knowledge of the existence of this effect can be important for the design of experiments involving laser driven chemistry.
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  • 26
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    Applied physics 35 (1984), S. 199-200 
    ISSN: 1432-0649
    Keywords: 42.60 ; 07.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We report results of harmonic mixing experiments between millimetric oscillators and FIR laser radiations up to 3 THz, using micrometer-size Schottky-barrier diodes. Signal-to-noise ratios suitable for precise frequency counting have been obtained for harmonic numbers up to 40.
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  • 27
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    Applied physics 35 (1984), S. 227-231 
    ISSN: 1432-0649
    Keywords: 42.55 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The feasibility of using the electrically excited XeF(C»A) excimer medium as an efficient wideband amplifier in the blue-green region of the spectrum has been investigated. Calculations show that for an intense blue-green optical flux input the amplification characteristics of XeF(C»A) improve, as a result of both bleaching of the pump induced absorbers and by additional production of XeF(C) level population. The removal of one of the major absorbing species, Xe** in the XeF (C»A) laser mixture by means of a pulsed ruby laser probe beam has been demonstrated.
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  • 28
    ISSN: 1432-0649
    Keywords: 42.60 ; 42.65
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We report the observation of coherent uv emission at 330.2±0.5 nm when sodium vapor in a heatpipe is irradiated with a pulsed visible dye laser with output wavelength in the 570–595 nm region. It is found that intense uv emission can be produced from Na atoms as well as from Na2 molecules. The excitation functions and their dependence on vapor density and laser power density are presented and the mechanisms for producing the emission are discussed.
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  • 29
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    Nutrient cycling in agroecosystems 5 (1984), S. 371-382 
    ISSN: 1573-0867
    Keywords: nitrogen ; phosphorus ; dry areas ; apparent recovery fraction ; fertilizer management
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Agronomic efficiency (AE) is defined as the increase in economic yield of a crop per unit fertilizer applied. Components of AE are physiological efficiency and apparent recovery fraction. The latter can be further separated into uptake efficiency and availability index. Ways to increase the nitrogen fertilizer use efficiency in rainfed agriculture through fertilizer management are discussed.
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  • 30
    ISSN: 1432-0649
    Keywords: 42.60 ; 42.55
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    Topics: Physics
    Notes: Abstract To improve the gain in the Orsay storage ring Free Electron Laser (FEL) experiment, the 17 period permanent magnet undulator has been modified to form an optical klystron (OK). We report the measurement of spontaneous emission and the effects on it of energy spread and angular spread. Gain and laser induced bunch lengthening measurements with the OK are also reported and are in very good agreement with the FEL classical theory. The spontaneous emission spectrum which is easy to measure with good signal to noise ratio, turns out to be a very good diagnostic tool forenergy spread and angular spread measurements on storage rings. The factor of four increase in the small gain obtained by converting the undulator NOEL into an OK was the critical factor in the recent operation of the ACO storage ring laser above threshold.
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  • 31
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    Applied physics 35 (1984), S. 31-36 
    ISSN: 1432-0649
    Keywords: 42.60 ; 33 ; 36
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    Topics: Physics
    Notes: Abstract A spectroscopic dye laser system-pumped by a Copper Vapor Laser (CVL)-has been built and optimized for different dye solutions operating in the spectral range from 530 to 890 nm. Conversion efficiencies up to 40% were reached in broad band operation, 24% with a prism expander grating cavity, and 20% in grazing incidence configuration, which operated at typical band widths of 3 GHz. Second harmonic generation (SHG) of the dye laser output produced tunable uv-radiation between 260 and 408 nm at conversion efficiencies ≦5%. Fundamental and SHG output were used for resonant ionization experiments in molecular beams.
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  • 32
    ISSN: 1432-0630
    Keywords: 42.60 ; 68.55 ; 61.80
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract New results are reported concerning the vanadium oxidation by cw CO2 laser irradiation in air at atmospheric pressure. Particular emphasis is paid both to the initial stage and the development of the oxidation process under the action of the laser radiation. Some aspects are finally discussed concerning the quantitative theoretical interpretation of the experimentally recorded data.
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  • 33
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    European journal of clinical pharmacology 26 (1984), S. 513-520 
    ISSN: 1432-1041
    Keywords: xipamide ; electrolyte excretion ; bioavailability ; elimination ; extrarenal clearance ; chronic renal failure ; furosemide ; hydrochlorothiazide ; amiloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a single oral dose of 40 mg xipamide on urinary excretion of Na+, K+, Cl−, Ca2+ and Mg2+ in healthy subjects and in patients with varying degrees of renal impairment was compared with various conventional diuretics. Xipamide caused marked excretion of Na+ and Cl−, whereas the diuretic produced only moderate kaliuresis; urinary excretion of Ca2+ was increased in proportion to Na+, like the loop diuretics. Xipamide affected electrolyte excretion even in patients with a creatinine clearance below 30 ml/min, as do the loop diuretics, too. Therefore, the pharmacodynamic characteristics of xipamide are more like those of a loop diuretic than of a thiazide. Xipamide was good bioavailable, its t1/2β was 7 h and urinary recovery of the undegraded drug was 40% of the given dose. In renal insufficiency, t1/2β increased from 7 to only 9 h, yielding a moderate increase in the AUC. Urinary recovery of the drug was reduced in proportion to the reduction in the creatinine clearance of the patient. Therefore, significant extrarenal elimination of the diuretic must be postulated, which suffices to prevent significant drug accumulation in renal failure.
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  • 34
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    European journal of clinical pharmacology 27 (1984), S. 105-110 
    ISSN: 1432-1041
    Keywords: phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
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  • 35
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    European journal of clinical pharmacology 27 (1984), S. 595-602 
    ISSN: 1432-1041
    Keywords: furosemide ; bioavailability ; generic tablet formulations ; intrasubject variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Intrasubject variation in bioavailability (rate and extent) and disposition of furosemide 40 mg was investigated using a repeated, randomized, double-blind cross-over study in 8 healthy subjects. Two generic tablet formulations (Lasix and Furix) and intravenous furosemide were compared on 6 separate days. Extensive intrasubject variability after oral administration was observed in AUC, mean absorption time (MAT) and urinary excretion. The variability (error variance) within the dosage forms was as large as that between the two generics. These variations most probably depended on the absorption process, since the repeated i.v. doses showed only marginal intrasubject variability. Absolute bioavailability was 56% for Lasix and 55% for Furix (AUC). The range was 20 to 84% between individuals and the maximal range within one individual was 20 to 61%. Confidence interval and Bayesian analysis showed a high probability of non-equivalence not only between but also within the generics when the separate cross-over experiments were analyzed (8 observations). When extending the analysis to 16 observations, bioequivalence was demonstrated for the two generic tablets. Rate of absorption, quantified as MAT, was 128 min for Lasix and 98 min for Furix (16 observations). Since MAT was significantly longer (p〈0.001) than the mean residence time after the i.v. dose (57 min), absorption was evidently the rate-limiting step in the overall kinetics of oral furosemide. Intraindividual variation in absorption is a confounding factor in bioavailability studies of furosemide using limited numbers of subjects. This is important to consider when designing and evaluating bioavailability studies for drugs showing these variations.
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  • 36
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    European journal of clinical pharmacology 26 (1984), S. 405-407 
    ISSN: 1432-1041
    Keywords: theophylline ; drug absorption ; bioavailability ; food intake ; sustained-release preparations ; Theolin Retard
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of theophylline from a sustained release tablet preparation (Theolin® Retard 300 mg) was studied in 10 subjects both when fasting and immediately after a standardized breakfast. Intravenous aminophylline was used as the reference material. Food did not influence the absorption from Theolin Retard. The bioavailability was complete (93% after 30 h) both with and without food, and no difference was found in the time to peak of the plasma concentration curve (7 h), or the mean residence time (14 h). The absorption characteristics, with predominantly zero order kinetics, did not change with concomitant intake of breakfast.
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  • 37
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    European journal of clinical pharmacology 27 (1984), S. 111-114 
    ISSN: 1432-1041
    Keywords: chlorambucil ; chronic lymphocytic leukaemia ; phenylacetic acid mustard ; food intake ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4–7.1) under fasting and 3.3 (range 1.3–7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.
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  • 38
    ISSN: 1432-1041
    Keywords: nitroglycerin ; plasma concentration ; transdermal administration ; bioavailability ; pharmacodynamics ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 6 healthy volunteers, intravenous infusions of nitroglycerin 4.8 and 10.6 µg/min yielded mean steady-state plasma concentrations of 0.5±0.02 and 0.82±0.04 ng/ml as determined by a gas chromatographic/mass spectrometric method. The plasma concentrations reached in the same subjects 17 h after application of Nitroderm TTS 5 and 10 with in vivo release rates of 3.7 and 5.7 µg/min were 0.28±0.01 and 0.37±0.01 ng/ml, respectively. Thus, 75% of the quantity of nitroglycerin released by the systems passed into the circulation. The inter-individual and intra-individual variations in plasma concentrations were similar for both modes of administration. The nitroglycerin-induced morphological changes in the fingerpulse wave were clearly dose-dependent, but it seems that this pharmacodynamic parameter is determined less by the plasma concentration than by the nitroglycerin content of the vascular wall.
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  • 39
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    European journal of clinical pharmacology 26 (1984), S. 133-135 
    ISSN: 1432-1041
    Keywords: co-dergocrine mesylate ; geriatric patients ; hydergine ; bioavailability ; steady state
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relative bioavailability of the newly developed formulation of co-dergocrine mesylate (Hydergine spezial, 1×4 mg) was determined in elderly patients under steady state conditions, with conventional Hydergine forte tablets (2×2 mg) as a reference. Both formulations were given once a day for 8 days in a randomised cross-over design. The areas under the curve showed that the bioavailability of the new tablet was about 30% higher (28±6.3%) than that of Hydergine forte. The peak plasma concentration was reached 3±0.9 h after administration. Because of its greater relative bioavailability higher plasma levels were found 2–24 hours after the Hydergine spezial formulation than after Hydergine forte tablets.
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  • 40
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    European journal of clinical pharmacology 26 (1984), S. 261-264 
    ISSN: 1432-1041
    Keywords: indomethacin capsules ; bioequivalence ; volunteers ; pharmacokinetics ; statistical significance ; bioavailability ; comparative bioequivalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Two, separate 6×6 Latin square cross-over bioequivalence studies were performed in adult male volunteers using 10 different indomethacin capsule preparations marketed in India together with the pure drug powder as the standard. The products were evaluated with respect to plasma level at various times up to 8 h following administration of a 50 mg (2 × 25 mg) dose. Plasma samples were analysed by a fluorimetric method. Various pharmacokinetic parameters were calculated according to a two compartment model. Statistical evaluation of the data employed analysis of variance for a cross-over design (ANOVA) and Duncan's multiple range test to ascertain the significance of differences between the products. Of the 10 products studied, two were found to be bioinequivalent.
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  • 41
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    European journal of clinical pharmacology 26 (1984), S. 463-470 
    ISSN: 1432-1041
    Keywords: dihydroergotamine ; 8′-hydroxy-dihydroergotamine ; plasma metabolites ; bioavailability ; receptor affinity ; healthy volunteers ; liver microsomal incubates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations and urinary excretion of dihydroergotamine and its metabolites have been measured after a single oral administration of 3 mg tritium-labelled drug to 6 male volunteers. The plasma level of non-volatile radioactivity declined biphasically with α- and β-phase half-lives of 2.1 h and 32.3 h, respectively. The peak plasma concentration was reached within 3.2h. Urinary excretion of total non-volatile radioactivity was low, amounting to 1.0% of the dose. The parent drug and four metabolites could be quantitated in urine and plasma samples. Metabolite 4 (8′-hydroxy-dihydroergotamine) was isolated from incubates of rat and monkey liver microsomal preparations. In human liver microsomal incubates, metabolite 4 was shown to be the primary metabolite of dihydroergotamine. In receptor binding studies performed with mammalian brain preparations, metabolite 4 had IC50-values at 6 monoaminergic binding sites similar to those of dihydroergotamine. Thus, it appears that the active principle consists at least of dihydroergotamine and its 8′-hydroxy derivative. As the concentration of metabolite 4 exceeded 5–7 times that of dihydroergotamine in urine and plasma, the bioavailability of dihydroergotamine should be reevaluated, taking into account the plasma concentrations of the parent drug and of its acitve metabolite, 8′-hydroxydihydroergotamine.
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  • 42
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    European journal of clinical pharmacology 26 (1984), S. 533-534 
    ISSN: 1432-1041
    Keywords: amiodarone ; bioavailability ; clearance estimation
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    Topics: Chemistry and Pharmacology , Medicine
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  • 43
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    European journal of clinical pharmacology 26 (1984), S. 125-127 
    ISSN: 1432-1041
    Keywords: nadolol ; pharmacokinetics ; plasma levels ; urinary excretion ; bioavailability ; circadian rhythm
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 7 healthy subjects (3 males and 4 females), the kinetics of nadolol was investigated after oral doses of 60 and 120 mg. The t1/2 was 14.0±1.8 h. The peak plasma level was doubled on doubling the dose (from 69±15 to 132±27 ng/ml, respectively) and the urinary excretion (13.5%) rose similarly. The half-life of elimination was longer at night than in the day, probably because of the slower nocturnal flow of urine.
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  • 44
    ISSN: 1432-1041
    Keywords: cimetidine ; cystic fibrosis ; bioavailability ; renal clearance ; renal function differences
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and metabolism of cimetidine were studied in five cystic fibrosis patients (mean age 12.6 years) after oral and intravenous administration. As compared to healthy adult volunteers, cystic fibrosis children had an elevated cimetidine total body clearance (474 vs 300 ml/min/m2) as well as renal clearance (293 vs 232 ml/min/m2) whether normalized for body weight or surface area differences. Cimetidine elimination was elevated in juvenile cystic fibrosis patients as compared to adult volunteers, however, it did not differ significantly from that previously seen in age matched children. There were no appreciable differences in cimetidine metabolism after either route of administration. Differences between adults and cystic fibrosis children were attributed to developmental and age related differences between the two groups. The recommended pediatric dose of 15 to 20 mg/kg, although four-fold greater than that used in adults, produces serum concentrations similar to those seen in adults, and is adequate for most juvenile cystic fibrosis patients.
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  • 45
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    European journal of clinical pharmacology 26 (1984), S. 197-207 
    ISSN: 1432-1041
    Keywords: furosemide ; bioavailability ; pharmacokinetics ; oral administration ; i.v. administration ; drug absorption ; moment analysis ; food effect ; dissolution effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Furosemide 40 mg was administered to 8 healthy subjects as an i.v. bolus dose, as 1 tablet in the fasting state, and as 1 tablet and a solution after food intake. The i.v. data gave a total body clearance of 162±10.8 ml/min and a renal clearance of 117±11.3 ml/min; the volume of distribution at steady state was 8.3±0.61. Oral administration gave a bioavailability of the tablet (fasting) of 51%. Food intake slightly reduced the bioavailability, but not to a significant extent. There was no significant difference in availability between the tablet and the solution. Moment analysis gave a mean residence time after the i.v. dose, MRTi.v., of 51±1.5 min. The mean absorption times (MAT) for all oral doses were significantly longer than the MRTi.v., indicating absorption rate-limited kinetics of furosemide. On average, food delayed the absorption by 60 min. The MAT for the tablet in the postprandial state was significantly longer than for the solution, indicating dissolution rate-limited absorption of the tablet.
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  • 46
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    European journal of clinical pharmacology 26 (1984), S. 271-273 
    ISSN: 1432-1041
    Keywords: cimetidine ; prednisolone ; aluminium phosphate ; antacids ; bioavailability ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten fasting subjects received 200 mg cimetidine orally either with water or 11 g aluminium phosphate mixture in a randomized, single dose, two-way cross-over study. Blood samples were taken for 12 h and urine was collected for 24 h. Cimetidine in plasma and urine was analysed by HPLC. There were no significant differences between the treatments with respect to peak plasma concentration, time to peak plasma concentration, area under the plasma concentration-time curve, and urinary excretion. In 12 healthy subjects the absorption of prednisolone was investigated when given alone and together with 11 g aluminium phosphate. Blood samples were taken over 16 h and prednisolone in plasma was analysed by HPLC. There were no significant differences in the values of area under curve (AUC), Cmax and tmax. The results indicate that aluminium phosphate does not reduce the bioavailability of cimetidine and prednisolone.
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  • 47
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    European journal of clinical pharmacology 26 (1984), S. 347-355 
    ISSN: 1432-1041
    Keywords: cimetidine ; cirrhosis ; pharmacokinetics ; bioavailability ; clearance reduction
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of impaired liver function on the pharmacokinetics of cimetidine was studied in 8 patients with advanced cirrhosis given single doses of 100 mg i.v. and 400 mg p.o. on separate days. Compared to a control group of 10 healthy volunteers, the total renal and nonrenal clearance was significantly reduced in the cirrhotic patients; (total plasma clearance mean ± SD) 356±181 vs 789±262 ml/min (p〈0.01); renal clearance (Clr) 296±100 vs 588±181 ml/min (p〈0.01) and nonrenal clearance (Clnr) 97±111 vs 205±89 ml/min (p〈0.05). Compared to published results for age-matched ulcer patients, both total and nonrenal clearance were lower whereas renal clearance was within the reported normal range. A significant reduction in volume of distribution (Vdβ) was found, from 2.1±0.1 l/kg in controls to 1.0±0.4l/kg, and in the patient group there was a significant correlation between Vdβ and total plasma clearance (r=0.72, p〈0.05). Volume of distribution in steady state (Vdss) did not differ from published results in age-matched controls. No significant change in half-life was found. Bioavailability, estimated by AUC-measurement, showed considerable patient variability (21–143%), with a mean of 70±39%. This was lower than in the controls. In contrast, measurement of urinary excretion showed higher bioavailability in the patients (66±23 vs 51±8%). No correlation was found between any of the kinetic parameters and the clinical and laboratory data. It is suggested that patients with advanced cirrhosis should be closely observed when given cimetidine, and a reduction in dose should be concidered if side effects are to be avoided.
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  • 48
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    European journal of clinical pharmacology 27 (1984), S. 105-110 
    ISSN: 1432-1041
    Keywords: phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
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  • 49
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    European journal of clinical pharmacology 27 (1984), S. 111-114 
    ISSN: 1432-1041
    Keywords: chlorambucil ; chronic lymphocytic leukaemia ; phenylacetic acid mustard ; food intake ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4–7.1) under fasting and 3.3 (range 1.3–7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.
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  • 50
    ISSN: 1432-1041
    Keywords: nitroglycerin ; plasma concentration ; transdermal administration ; bioavailability ; pharmacodynamics ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 6 healthy volunteers, intravenous infusions of nitroglycerin 4.8 and 10.6 µg/min yielded mean steady-state plasma concentrations of 0.5±0.02 and 0.82±0.04 ng/ml as determined by a gas chromatographic/mass spectrometric method. The plasma concentrations reached in the same subjects 17 h after application of Nitroderm TTS 5 and 10 with in vivo release rates of 3.7 and 5.7 µg/min were 0.28±0.01 and 0.37±0.01 ng/ml, respectively. Thus, 75% of the quantity of nitroglycerin released by the systems passed into the circulation. The inter-individual and intra-individual variations in plasma concentrations were similar for both modes of administration. The nitroglycerin-induced morphological changes in the fingerpulse wave were clearly dose-dependent, but it seems that this pharmacodynamic parameter is determined less by the plasma concentration than by the nitroglycerin content of the vascular wall.
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  • 51
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    European journal of clinical pharmacology 27 (1984), S. 367-369 
    ISSN: 1432-1041
    Keywords: flurbiprofen ; syrup ; suppository ; kinetics ; children ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight subjects, aged 6–12 years and weighing 18.8–36.7 kg, received single doses of flurbiprofen 50 or 75 mg (corresponding to 1.4–2.7 mg/kg) as syrup and suppository in a Latin square design. Half-life (2.7–3.2 h), elimination constant (0.22–0.26 h−1), area under the plasma level curve (72.4–77.3 µg·h·ml−1) and time to reach the concentration peak (1–0.75 h) were similar after the syrup and suppository. Flurbiprofen showed equivalent bioavailability after oral and rectal administration and the same pharmacokinetic profile was confirmed in children as observed in adults.
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  • 52
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    European journal of clinical pharmacology 27 (1984), S. 623-624 
    ISSN: 1432-1041
    Keywords: cimetidine ; bioavailability ; renal clearance
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    Topics: Chemistry and Pharmacology , Medicine
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  • 53
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    European journal of clinical pharmacology 26 (1984), S. 269-270 
    ISSN: 1432-1041
    Keywords: cyclophosphamide ; cytostatic drug ; cancer therapy ; female breast cancer ; bioavailability ; rapid release formulations ; gastric juice resistant formulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Cyclophosphamide (CP) is an alkylating cytostatic compound, which is activated to its cytotoxic form in the liver [1]. Since the therapeutic range of CP in the treatment of human tumours, is small like other cytostatics, a constant high bioavailability is essential for its oral administration. Although CP has become one of the most widely used cytostatics [2], there do not appear to have been any bioavailability investigations providing the necessary information. The development of a very sensitive gas chromatographic analytical method has now permited investigation of the pharmacokinetics of oral CP in conventional clinical doses [3, 4, 5, 6].
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  • 54
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    European journal of clinical pharmacology 27 (1984), S. 85-89 
    ISSN: 1432-1041
    Keywords: digitoxin ; radioimmunoassay ; pharmacokinetics ; bioavailability ; digitoxin metabolites
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of digitoxin were examined in six normal human subjects using an assay that separates digitoxin from its metabolites. After intravenous administration, the mean systemic clearance was 2.44 ml/min; the volume of distribution was 0.47 l/kg; and the elimination half-life was 6.5 days. After oral administration, the elimination half-life was 5.8 days. The bioavailability was 81.5% using the specific assay. Using a non-specific, direct serum digitoxin radioimmunoassay the bioavailability was 98.0%. Assay of aqueous fractions from extracted serum samples indicated higher levels of water-soluble metabolites following oral compared to intravenous digitoxin administration. These findings suggest that previously reported values for digitoxin bioavailability using non-specific methods may be falsely elevated due to the presence of digitoxin metabolites in serum.
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  • 55
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    European journal of clinical pharmacology 27 (1984), S. 85-89 
    ISSN: 1432-1041
    Keywords: digitoxin ; radioimmunoassay ; pharmacokinetics ; bioavailability ; digitoxin metabolites
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of digitoxin were examined in six normal human subjects using an assay that separates digitoxin from its metabolites. After intravenous administration, the mean systemic clearance was 2.44 ml/min; the volume of distribution was 0.47 l/kg; and the elimination half-life was 6.5 days. After oral administration, the elimination half-life was 5.8 days. The bioavailability was 81.5% using the specific assay. Using a non-specific, direct serum digitoxin radioimmunoassay the bioavailability was 98.0%. Assay of aqueous fractions from extracted serum samples indicated higher levels of water-soluble metabolites following oral compared to intravenous digitoxin administration. These findings suggest that previously reported values for digitoxin bioavailability using non-specific methods may be falsely elevated due to the presence of digitoxin metabolites in serum.
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  • 56
    ISSN: 1573-8744
    Keywords: hydrochlorothiazide ; triamterene ; hydroxytriamterene sulfate ; pharmacokinetics ; bioavailability ; renal clearance ; interaction
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Hydrochlorothiazide, triamterene, and hydroxytriamterene sulfate were monitored in the plasma and urine of 24 healthy young men taking single doses of a liquid preparation containing both hydrochlorothiazide and triameterene, liquid preparations containing either of these drugs alone, and a combination tablet recently formulated with a dose ratio of hydrochlorothiazide: triamterene (1∶1,5) found to give optimal potassium-sparing effect. In contradiction to a recent publication, no interaction between the drugs affecting the bioavailability or renal clearance of either could be demonstrated. The previous report of drug-drug interaction probably arose from formulationrelated problems with bioavailability from the two capsule and two tablet products which had been studied. A well-formulated hydrochlorothiazide-triamterene combination tablet promotes plasma concentrations and urinary excretion of hydrochlorothiazide, triamterene, and hydroxytriamterene sulfate which are virtually identical to those seen after either a combination liquid dosage form or simple liquid forms containing only one of the two drugs.
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  • 57
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    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 289-313 
    ISSN: 1573-8744
    Keywords: protein binding ; pharmacokinetics ; bioavailability ; disopyramide ; heart failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and bioavailability of total (bound plus unbound) and unbound disopyramide were compared following the simultaneous administration of an oral dose of disopyramide and an intravenous dose of14C-disopyramide in five normal volunteers and in 11 patients with congestive heart failure. The binding of disopyramide varied between 60 and 92% in patients and between 81 and 88% in normal subjects at postequilibrium drug concentrations of 10−7M. The binding of disopyramide to serum protein was concentration-dependent in all study subjects at serum concentrations achieved following drug administration. The association constant for the first binding site in serum from normal subjects and patients averaged 8.7X105 M−1 and 4.4X10 5 M−1, respectively (p 〈 0.05). The unbound clearance of disopyramide averaged 277ml/min and 209 ml/min in normal subjects and in patients (p 〈 0.05). When normalized for body weight, the unbound clearance between patients and normal subjects was not significantly different. The elimination half-life of unbound concentrations in normal subjects and in patients averaged 4.9 and 6.1 h, respectively (p 〈 0.05). The clearance and elimination half-life of total disopyramide was the same in both groups. Although the bioavailability of disopyramide averaged 0.85 in both groups, it was more variable in patients owing to the variability in the fraction of the dose absorbed. The unbound renal clearance and volume of distribution at steady state of disopyramide was related to cardiac index. The ratio of elimination half-lives of total and unbound disopyramide was related to the extent of serum protein binding.
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  • 58
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    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 315-331 
    ISSN: 1573-8744
    Keywords: theophylline ; antacids ; interaction ; bioavailability ; steady state
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    Topics: Chemistry and Pharmacology
    Notes: Abstract We examined the influence of a large-volume, therapeutic antacid regimen, administered for three full days, on the steady-state bioavailability of a conventional-release and sustained-release theophylline product, Aminophyllin and Theodur, respectively. Nine stable asthmatics voluntarily completed a four-phase investigation requiring a total stay of 12 days in the Clinical Research Unit. The treatments consisted of administration of the formulations mentioned with and without antacids to each patient in a randomized sequence. Four patients participated in an additional phase where antacids were administered q2h around the clock for three days. After coadministration of theophylline plus antacids for two days, theophylline therapy was discontinued while numerous blood samples were obtained over 22 hr and analyzed for theophylline content via radioimmunoassay. Antacids had no predictable, consistent influence on theophylline absorption rate as determined by the absorption rate constant, the time to maximal theophylline concentration, or the lag time for theophylline absorption. Antacids had no detectable influence on theophylline elimination half-life and had no consistent, statistically significant effect on the extent of theophylline bioavailability, according to measurements of maximal concentration, AUCmeasured over the appropriate steady-state dosing interval, or elimination-rate adjusted AUC.The substantial intraindividual changes for all parameters of theophylline bioavailability that occurred for control and treatment phases likely represent spontaneous, random between-day variability in theophylline disposition independent of antacid administration, as evidenced by the comparability of the percent coefficient of variation for parameters of biovailability across all phases. Our data demonstrate that therapeutic antacid administration has no effect on steady-state theophylline bioavailability and does not alter the intrinsic variability in theophylline absorption. Based on the results of our data, it is unlikely that a clinically significant (〉20%) decrease in theophylline absorption would occur in any patient treated intensively with antacids concurrently.
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  • 59
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    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 83-91 
    ISSN: 1573-8744
    Keywords: bioavailability ; bioequivalence ; hypothesis tests ; sample size determination
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    Topics: Chemistry and Pharmacology
    Notes: Abstract The clinical problem of testing for equivalence in comparative bioavailability trials is restated in terms of the proper statistical hypotheses. A simple t-test procedure for these hypotheses has been devloped that is more powerful than the methods based on usual (shortest) and symmetric confidence intervals. In this note, this new procedure is explained and an example is given, including the method for sample size determination.
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  • 60
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    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 437-450 
    ISSN: 1573-8744
    Keywords: first-pass ; bioavailability ; Michaelis-Menten ; volume of distribution ; absorption rate constant
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Two approaches used for bioavailability determination of drugs with Michaelis-Menten elimination kinetics were examined by computer simulation. The first method involved treating the drug as though its clearance remained constant during elimination, and the conventional method of taking the ratio of areas under the curve resulting from the oral and intravenous doses was used to calculate bioavailability. The second approach involved using the Michaelis parameters, Vmax and Km,to determine concentration dependent clearance values, but based these calculations on peripheral drug concentrations rather than on concentrations entering or in the liver. We have developed a simulation method that was used to test the accuracy of the above two methods. In the simulations described, Vmax, Km,and hepatic blood flow were chosen to represent a drug with an extraction ratio of 0.9 under linear conditions, but with Michaelis-Menten kinetics occurring at the doses given. Absorption was assumed to be first-order, and metabolism was assumed to occur only in the liver. These simulations showed that the most accurate determination of bioavailability requires knowledge of the direct contribution of oral absorption to the concentration of drug entering the liver. Unexpectedly, the results also showed that if a drug has a large volume of distribution or a large absorption rate constant, or both, use of the much simpler conventional method of bioavailability determination may be appropriate even in cases where the degree of saturation is substantial.
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    Hydrobiologia 111 (1984), S. 49-56 
    ISSN: 1573-5117
    Keywords: nutrient enrichment ; yield coefficient ; nitrogen ; phosphorus ; mass culturing ; phytoplankton ; sea water
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    Topics: Biology
    Notes: Abstract Natural phytoplankton of Cabo Frio area was grown in 42 m-deep artificially upwelled seawater enriched with increasing concentrations of nitrogen or phosphorus. Respective values allowing maximum biomass, maximum uptake of initial reserve and maximum yield coefficient are rather conflicting. Notwithstanding, respective values of 75 µg at 1−1 nitrogen and 5 µg at 1−1 phosphorus, and therefore N:P = 15, appeared to be the best compromise for initial nutrient levels.
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    Hydrobiologia 112 (1984), S. 131-136 
    ISSN: 1573-5117
    Keywords: reed ; harvest ; nitrogen ; phosphorus ; redox potential ; oxygen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract An investigation of the effects of repeated winter harvest and removal of dry reed culms on water and sediment chemistry was made in a shallow lake dominated by closed, monospecific reed stands. The oxygen concentration and redox potential in the water, as well as temperature, showed regular diurnal fluctuations inside the reed stands. Ammonium and nitrate + nitrite did not exhibit diurnal fluctuations and differences between a harvested and an unharvested reed area were small. Molybdate reactive phosphorus (MRP) concentration was higher in the unharvested area. Because the winter harvest caused an almost doubling of shoot production compared to the unharvested area, net addition of reed litter (leaves, stubble and culms) to the sediment of the harvested area was similar to that of the unharvested area. It is concluded that removal of reed culms in winter has the largest effect on microclimate in spring, and that the rate of mineralization and reducing intensity in the substrate are not immediately affected. Significantly higher summer standing crop of reed after harvest may have caused lower phosphate concentration in the water column and sediment interstitial water.
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  • 63
    ISSN: 1573-5117
    Keywords: enrichment ; phosphorus ; nitrogen ; phytoplankton ; tropical reservoir
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effects of enrichment with phosphate (0–500 µg. 1−1) and forms of nitrogen (nitrate, nitrite, ammonia an and urea) (0–3500 µgg. −1) on the phytoplankton growth of Lobo Reservoir (Brazil) were studied in July, 1979. Suspended matter, chlorophyll a, cell concentrations and the carotenoid:cchlorophyll ratio were estimated following 14 days of ‘in situ’ incubation. Phosphate alone caused no significant effects, but enrichment with nitrogen caused a substantial increase on the growth of phytoplankton. Comparison between the different forms of nitrogen showed insignificant effects after their additions with 350 µg. −1 and in combination with phosphate. However, when nitrogen was added in large quantities (3 500 µg. −1), significant differences between the nitrogeneous forms were found, with urea causing the strongest effect. In July, nitrogen is mhe main limiting nutrient to phytoplankton growth of Lobo Reservoir.
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  • 64
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    European journal of nutrition 22 (1983), S. 185-194 
    ISSN: 1436-6215
    Keywords: sugar substitutes ; D-glucose ; bioavailability ; D-glucitol (D-sorbitol) ; D-mannitol ; Palatinit® ; D-glucosyl-α(1→1)-D-mannitol ; D-glucosyl-α(1→6)-D-glucitol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Zur Vertiefung des Verständnisses vom Stoffwechsel des Zuckeraustauschstoffes Palatinit® wurden seine zwei Bestandteile D-Glucosyl-α(1→1)-D-mannit und D-Glucosyl-α(1→6)-D-glucit [D-Glucosyl-α(1→6)-D-sorbit] nach dem Verfahren von Karimzadegan et al. auf ihre Glucose-Bioverfügbarkeit an ketotischen Ratten untersucht. Bei Umwandlungsraten in Glucose von 6 bzw. 20 % für Mannit und Glucit (Sorbit) sowie von 39 bzw. 42% für Glucosylmannit und Glucosylglucit erhält demnach der metabolische Glucose-Pool nicht das volle Glucose-Äquivalent aus diesen Verbindungen. Von dem Anteil an präformierter Glucose in den Glucosylhexiten — theoretisches Maximum 50 % — sind nur 36 % aus Glucosylmannit bzw. 32 % aus Glucosylglucit bioverfügbar. Die im Vergleich zur Theorie verminderte Bioverfügbarkeit von Glucose aus Palatinit® wird auf partiellen mikrobiellen Abbau in unteren Darmabschnitten zurückgeführt. Die an Ratten erhaltenen Ergebnisse werden auch für alle anderen Spezies gelten, welche in Caecum und/oder Colon Kohlenhydrate vergären. Die Unterschiede zwischen D-Glucosyl-α(1→1)-D-mannit und D-Glucosyl-α(1→6)-D-glucit werden durch unterschiedliche Verzögerung der Glucoseresorption im Dünndarm, wo auch D-Glucit angreift, bedingt. Die Ermittlung der Glucose-Bioverfügbarkeit gewährt weitgehende Einblicke in das Schicksal von Kohlenhydraten einschließlich der Symbiose zwischen Säugetier und Mikroorganismen im Dickdarm. Da ein ziemlich vollständiger Überblick über die metabolischen Konsequenzen nach ihrer Zufuhr erhalten wird, sollte das Verfahren zur Messung der Bioverfügbarkeit von Glucose daher bei Abschätzungen der Lebensmittelsicherheit anderer Zuckeraustauschstoffe ebenfalls angewandt werden.
    Notes: Summary For the sake of metabolic insight into the fate of the sugar substitute Palatinit®, its two components D-glucosyl-α(1→1)-D-mannitol and D-glucosyl-α(1→6)-D-glucitol [D-glucosyl-α-(1→6)-D-sorbitol] were assayed for glucose bioavailability by the procedure of Karimzadegan et al. using ketotic rats. With conversion rates into glucose of 6 and 20 %, respectively, for free mannitol and glucitol (sorbitol), 39 % for glucosylmannitol and 42 % for glucosylglucitol, the metabolic glucose pool of the rat does not receive the full carbohydrate complement of these compounds. The preformed glucose moiety of the glucosylhexitols is bioavailable by 36 and 32 %, respectively, from glucosylmannitol and glucosylglucitol, with 50 % as theoretical maximum. Less than theoretical bioavailability of glucose from Palatinit® is ascribed to microbial attack in the hindgut. The data on rats are held valid also for other species demonstrating carbohydrate fermentation in the caecum and/or colon. Differences between D-glucosyl-α(1→1)-D-mannitol and D-glucosyl-α(1→6)-D-glucitol are caused by a differential delay of glucose absorption in the small intestine, also exerted by D-glucitol. The deep metabolic insight offered by the glucose bioavailability assay into the fate of carbohydrates includes the mammal-microbial symbiosis in the large bowel. Since a rather complete survey of the metabolic consequences after their intake can be obtained, the assay system should be generally applied in assessments of food safety also of other sugar substitutes.
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  • 65
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    Applied physics 30 (1983), S. 135-142 
    ISSN: 1432-0649
    Keywords: 42.55 ; 42.60 ; 42.80
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract An analysis of cw synchronously pumped dye lasers is presented. Under the assumption that the cavity (tuning element) bandwidth is much wider than the bandwidth of the transform limited pulses generated, the pulse forming dynamics is rigorously treated. It is shown that for a finite mismatch between the lengths of the dye and the pump lasers, a steady-state pulse develops in the dye laser cavity with a conserved pulseshape. The characteristics (energy, shape, peak power, duration) of these pulses of ultimate width are quantitatively determined as a function of cavity mismatch. An analytical solution for the pulse envelope is determined, which yieldsI(t)∝Sech2(t/t p ) to a good approximation.
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  • 66
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    Applied physics 30 (1983), S. 161-176 
    ISSN: 1432-0649
    Keywords: 32 ; 42.50 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A new method for determining trace amounts of elements in a substance has been developed. It is based on thermal evaporation and atomization of a substance in vacuum and detection of the released trace atoms by the laser stepwise photoionization technique. A rather effective way of detecting atoms is their multistep excitation to Rydberg states by the radiation of tunable dye lasers with their subsequent ionization by electric field pulses. The analytical laser spectrometer consisting of several tunable, pulsed dye lasers, a vacuum chamber with an atomizer and a recording system is described. The microimpurities of elements have been detected in pure materials: the contents of Na impurities in CdS crystals (2×10−6%) and Al impurities in germanium (2×10−7%). The detection limit of about 10−9% was determined. A technique for direct determination of the content of elements in natural water and human blood is described. A high sensitivity, universality and other merits of the method enable it to be used in determining traces of many important elements at a level of 10−8 to 10−11% almost in any matrix.
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  • 67
    ISSN: 1432-0649
    Keywords: 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We have shown that distributed feedback dye lasers are capable of generating single transform-limited pulses of 1.6–3.5 ps duration when pumped by a mode-locked Nd: YAG laser. A short-pulse amplifier has been constructed in which the level of amplified spontaneous emission could be kept below 10−3 by properly taking into account the polarization anisotropy of the gain and by precise timing of the pump pulses. A sensitive autocorrelator is described which allows to measure pulse duration in a single shot.
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  • 68
    ISSN: 1432-0649
    Keywords: 42.60 ; 42.65 ; 61.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Absorption recovery kinetics data on the picosecond time-scale of a high signalto-noise ratio can be obtained by using continuously operating synchronously modelocked dye lasers. We show that such data make it possible to determine multiple exponential decays with small differences in rate constants. We also show that an absolute prerequisite to accomplish this is that the measurements are performed at a number of different wavelengths, and that the decays are monitored in a time interval corresponding to several lifetimes. These considerations are demonstrated by measurements on two carbocyanine dyes, DQOCI and pinacyanol, respectively.
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  • 69
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    Applied physics 32 (1983), S. 127-135 
    ISSN: 1432-0649
    Keywords: 42.55 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract A cw uv copper hollow cathode laser is described, which could be operated for a longer time duration with an output power of 7 mW in the 260 nm region. A double-cathode configuration with a protection for the mirrors from metal-vapour deposition is presented. Characteristics of the laser output power, the spontaneous emission, and the ion densities in the negative glow were measured as depending on the discharge current, the neon gas pressure, and the size of the cathode slit. The observed saturation of the laser output power at high discharge current (1 A/cm2) and the optimum slot size are discussed.
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  • 70
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    Applied physics 32 (1983), S. 119-122 
    ISSN: 1432-0649
    Keywords: 42.80 ; 42.60
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    Topics: Physics
    Notes: Abstract The model which reproduces accurately and conveniently the waveform of the amplitude modulated cw laser light in the TEM00 mode by a mechanical chopper is developed. It is found that its predictions are in good agreement with the strict, completely accurate but rather lengthy and inconvenient treatment and with the experiment. The criterion for the efficient amplitude modulation of the laser light by a mechanical chopper is formulated.
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  • 71
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    Applied physics 31 (1983), S. 15-17 
    ISSN: 1432-0649
    Keywords: 35 ; 07.65 ; 42.60
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    Topics: Physics
    Notes: Abstract An absorption method which permits time-selective measurements at different wavelengths has been developed in order to explore magnetic field effects on photoinduced electron transfer reactions in linked and unlinked donor-acceptor systems.
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  • 72
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    Applied physics 32 (1983), S. 7-8 
    ISSN: 1432-0649
    Keywords: 42.60 ; 42.80
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    Topics: Physics
    Notes: Abstract Bistable operation of a dual-wavelength synchronously mode-locked cw dye laser is reported. Wavelength switching is found to depend on the pump power and the dye laser cavity lengths.
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  • 73
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    Applied physics 30 (1983), S. 29-33 
    ISSN: 1432-0649
    Keywords: 42.55 ; 42.60
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    Topics: Physics
    Notes: Abstract This report describes an experimental examination of the output characteristics of the continuous-wave (cw) carbon monoxide flame chemical laser (FCL) of the CS2/O2/N2O type in case of small CS2/O2 reactants ratios (tipically CS2/O2≦1/10). A linear burner which gives a homogeneous and stable flame was used during the experimental study. The measurements of temperature distribution in CS2/O2 as well as CS2/O2/N2O flames show maximum temperatures of 1040 and 890 K, respectively. The addition of nitrous oxide (N2O) leads to dramatically enhanced output laser power caused primarily by V−V transfer processes. A chemical efficiency, based on the reaction O+CS→CO*+S, of 3% was achieved. The spectral composition of the CO FCL of the CS2/O2/N2O type shows lasing in the region from 5.130 to 5.586 μm. Experimental results were obtained with a nondispersive optical cavity.
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  • 74
    ISSN: 1432-0649
    Keywords: 82.50 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The initial stage of thermochemical instability induced by an absorbing inclusion within a transparent matrix, which irradiated by a laser beam, is studied. The instability results in a low threshold (formally non-threshold) optical breakdown of the matrix. It is brought about by the additional absorption of the laser light by the products of the chemical reactions in the matrix. The instability is characterized by a certain induction time when the rate of the chemical reactions is almost steady. When the induction is over, their rate rapidly increases. Theoretical estimate of the induction time are offered. The experimental study of the induction time dependence on the laser-beam intensity confirmed the theoretical estimation.
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  • 75
    ISSN: 1432-0649
    Keywords: 82.50 ; 82.40 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Isotope separation of tritium from deuterium in heavy water was attempted by CO2-laser-induced, highly-selective multiphoton dissociation of C2TF5 present in C2DF5. Single-step T/D separation factors exceeding 3000, 1000, and 500 were attained, respectively, for the first time with CO2 laser 10P(34) 931.0 cm−1 at 10, 20, and 30 Torr pentafluoroethane pressures at −78 °C (i.e., equivalent to 15, 30, and 45 Torr at room temperature).
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  • 76
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    Applied physics 32 (1983), S. 123-125 
    ISSN: 1432-0649
    Keywords: 42.60
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    Topics: Physics
    Notes: Abstract Short (〈0.5 ns) ultraviolet laser pulse generation by quenching of resonator transients is described. An output energy of 100–150 nJ at λ=340 nm is obtained using a pump energy of only 5–7 mJ at 308 nm. This pulse was amplified up to 100 μJ by a two stage amplifier.
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  • 77
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    Applied physics 30 (1983), S. 5-10 
    ISSN: 1432-0649
    Keywords: 42.60
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    Topics: Physics
    Notes: Abstract Bi-directional and folded laser amplifiers are analysed in the constant intensity approximation. Simple analytical expressions are developed for gain, output intensity and extraction efficiency. The analysis is applied to electron-beam pumped KrF lasers and expressions for saturation intensity, small-signal gain coefficient and intrinsic efficiency in terms of gas composition and pump power per unit volume are given. The problem of fluorine burn-up in KrF lasers is discussed. Under certain conditions the analysis is shown to be equally applicable to oscillators and comparison is made with previous experimental results and computer code predictions.
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  • 78
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    Applied physics 30 (1983), S. 99-104 
    ISSN: 1432-0649
    Keywords: 42.60 ; 07.65
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    Topics: Physics
    Notes: Abstract Some new experimental data on the time development of ultrashort superfluorescence (SF) in the dye solution are presented. The correlation between temporal behaviour change and the change of the spectral and spatial intensity distribution gives direct evidence of the important role of the selffocusing phenomenon in the formation of the ultrashort SF pulse synchronized with the pumping one. The oriental relaxation of solvent molecules in the dye solution not only influences the duration of the dye SF via the selffocusing mechanism but also causes a temporal change of spontaneous emission spectrum. At least two different relaxation times were found in the fluorescence spectrum of the dye in several polar solutions.
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  • 79
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    Applied physics 31 (1983), S. 193-199 
    ISSN: 1432-0649
    Keywords: 42.60 ; 42.65
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    Topics: Physics
    Notes: Abstract It is shown that LiF crystals with F 2 − colour centers may be used in lasers for cavity Q-switching and in high-power Nd: glass laser systems for, increasing the contrast and the self-excitation threshold. Also Lif crystals with F 2 − centers are successfully used for the generation of ultrashort pulses, for the generation of difference frequencies in the ir spectral range and in intracavity spectroscopy experiments.
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  • 80
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    Applied physics 32 (1983), S. 49-52 
    ISSN: 1432-0649
    Keywords: 42.60 ; 42.65
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    Topics: Physics
    Notes: Abstract Methods for simultaneous measurements of more than one flow velocity component using coherent Raman spectroscopy are proposed. It is demonstrated that using a kilowatt broad-band probe pulse (3–30 GHz) along with a megawatt narrow-band pump pulse (∼100 MHz), coherent Raman signal resulting from a single laser pulse is sufficient to produce a high-resolution Raman spectrum for a velocity measurement.
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  • 81
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    Applied physics 32 (1983), S. 39-42 
    ISSN: 1432-0649
    Keywords: 42.60 ; 42.65.C
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    Topics: Physics
    Notes: Abstract System parameters of an optical parametric generator pumped by the third harmonic of a Nd:glass laser are presented. The tuning range extends from 5700 to 22,700 cm−1; i.e., it covers a frequency range of 17,000 cm−1. Experimental data on spectral bandwidths, conversion efficiencies, and pulse shape are discussed. A pump beam with a divergence of four degrees simultaneously generates the entire visible spectrum (blue to red) separated by the angle of emission.
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  • 82
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    Applied physics 32 (1983), S. 113-118 
    ISSN: 1432-0649
    Keywords: 42.60 ; 92.60T ; 92.65
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Monitoring of the height distribution of atmospheric ozone up to 50 km is being performed with a ground-based lidar system, which has been in operation since October 1982 on the summit of Zugspitze in the German Alps. Daily and monthly averages of the ozone profile are being obtained with high precision. Furthermore, stratospheric aerosol layers, originating from the eruption of El Chichon volcano in Mexico in sping 1982 are being recorded.
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  • 83
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    Applied physics 31 (1983), S. 71-74 
    ISSN: 1432-0630
    Keywords: 42.60 ; 61.80 ; 78.50
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract By annealing Si layers amorphised by ion-implantation with a cw CO2 laser beam in oxygen rich environments, it has been possible to incorporate O atoms into the recrystallized lattice. Absorption measurements on such regrown layers by infrared spectrometry have shown that the impurities are preferentially bonded into substitutional lattice sites, rather than existing interstitially. Supplementary RHEED studies have indicated thatβ-cristobalite, a crystalline form of SiO2, has been formed. These investigations highlight the importance of the ambient during cw laser annealing.
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    Applied physics 32 (1983), S. 159-161 
    ISSN: 1432-0630
    Keywords: 66.30 ; 61.70 ; 42.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The entire sodium ion content of sodiumβ″ alumina (Na1.67Mg0.67Al10.33O17) can be replaced with a variety of lanthanide ions by simple diffusion reactions at moderate temperatures (500–700°C). Lanthanideβ″ alumina crystals are hard, clear, chemically stable, and have well-defined crystal structures. The fluorescence spectrum of Nd3+ inβ″ alumina is similar to that in YAG. The lifetime of the4 F 3/2 state of Nd3+ in completely-exchangedβ″ alumina (350μs at 1021 Nd3+ cm−3) is about 45% longer than in YAG (240μs at 1020Nd3+ cm−3). The lanthanideβ″ aluminas may be of considerable interest as new phosphor and laser host materials.
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    European journal of clinical pharmacology 24 (1983), S. 127-136 
    ISSN: 1432-1041
    Keywords: statistical analysis ; nonparametric statistical methods ; bioavailability ; confidence interval ; ANOVA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary For a two-way cross-over design, which appears to be the most common experimental design in bioavailability studies, 95%-confidence limits for expected bioavailability can be obtained by classical analysis of variance (ANOVA). If symmetry of the confidence interval is desired about zero (differences) or unity (ratios) rather than about the corresponding point estimator, Westlake's modification can be used. Two nonparametric methods and their adaptations to bioavailability ratios are reviewed, one based on Wilcoxon's signed rank test (Tukey), and the other on Pitman's permutation test. The necessary assumptions and the merits of these procedures are discussed. The methods are illustrated by an example of a comparative bioavailability study. A FORTRAN program facilitating the procedures is available from the authors upon request.
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    European journal of clinical pharmacology 24 (1983), S. 791-796 
    ISSN: 1432-1041
    Keywords: furosemide ; bioavailability ; diuretic effect ; urine sodium ; urine potassium ; power of ANOVA ; tablet formulations ; urinary flow rate ; normal volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relative bioavailability and diuretic effect of 2 commercially available tablet preparations of furosemide 40 mg was examined in 10 healthy male volunteers. A close linear relationship between the urinary excretion rate of furosemide and the rate of sodium ion excretion in urine and/or flow rate of urine was demonstrated. There were no significant differences in the urinary excretion of furosemide, sodium and potassium ions or urinary volume following the oral doses. The difference in drug content affected the urinary recovery of furosemide over 24 h but had no effect on the pharmacological response. The analytical power of ANOVA using the various parameters of the responses to furosemide was no lower than when the parameters of urinary excretion of furosemide were used.
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  • 87
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    European journal of clinical pharmacology 25 (1983), S. 237-241 
    ISSN: 1432-1041
    Keywords: triamterene ; bioavailability ; pharmacokinetics ; metabolism ; hydroxy triamterene sulphate ; urinary excretion ; i.v. administration ; first-pass-effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. The formation of OH-TA-ester was very rapid and the concentration of the metabolite exceeded that of TA at all times. After i.v. administration the urinary recovery of TA and OH-TA-ester was 4.4% and 50.9%, respectively. The bioavailability of TA was 52%, corresponding to absorption of 83%. TA is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active.
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    European journal of clinical pharmacology 25 (1983), S. 449-453 
    ISSN: 1432-1041
    Keywords: canrenone ; pharmacokinetics ; plasma level ; bioavailability ; urinary excretion ; spironolactone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy male volunteers received canrenoate-K 200 mg (Sincomen® pro injectione) by intravenous injection and one week later spironolactone 200 mg (Sincomen®-100) orally. Plasma levels and urinary excretion of unchanged canrenone were determined up to 24 h by a specific HPLC method. Following intravenous administration, the maximum plasma level of 2066±876 ng/ml was found after 29±15 min and thereafter the concentration declined with a half-life of 3.7±1.2 h. Total clearance was 4.2±1.7 ml/min·kg. After oral ingestion, the maximum concentration of 177±33 ng/ml was observed at 4.4±0.9 h. The absolute bioavailability of canrenone was 25±9%. Within 24 h, respectively 0.4 and 0.6 mg, canrenone were excreted by the kidney after intravenous and oral administration. The half-life of elimination was 4.9±1.8 h (i.v.) and 3.9±1.2 h (p.o.).
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    European journal of clinical pharmacology 24 (1983), S. 103-108 
    ISSN: 1432-1041
    Keywords: dexamethasone ; bioavailability ; pharmacokinetics ; ‘first-pass’ effect ; pre-systemic elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and oral biovailability of dexamethasone were studied in 6 patients with neurological disease being treated with high dosages of the drug. A specific high performance liquid chromatographic assay was used to measure dexamethasone concentrations. Unlike the previously published mean figure of 0.78 for the oral bioavailability of the drug given in single doses to healthy volunteers, the mean bioavailability of dexamethasone in the patients studied was 0.53±SD 0.40. It appeared more likely that this incomplete bioavailability was due to presystemic elimination than to poor absorption. The intravenous clearance of the drug was relatively high (0.4902±SD 2291 l kg−1, approximately 65% of expected hepatic plasma flow), the oral clearance higher (2.5804±SD 3.2181 l kg−1 h−1) while the absorption rate constant (4.8729±8.4998 h−1), suggested rapid absorption after oral administration. Prior phenytoin and possibly prior dexamethasone therapy is likely to have contributed to the higher clearance values of the drug in these patients than the values reported in healthy volunteers after single dose studies.
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  • 90
    ISSN: 1432-1041
    Keywords: oxmetidine ; pharmacokinetics ; bioavailability ; plasma half-life ; clearance ; oral dose ; i.v. dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration curves and urinary excretion of oxmetidine after administration of single i.v. (100 mg) and oral (200 mg) doses have been studied in 11 patients with peptic ulcer disease. The mean bioavailability of the drug was 70% (range 53–91%). After intravenous administration, the mean plasmat 1/2β was 3.0 h, the mean apparent volume of distribution 0.7 l/kg, the mean total plasma clearance 12.3 l/h and the mean plasma renal clearance was 0.7 l/h. Following intravenous and oral administration an average of 6% and 3%, respectively, of unchanged drug was found in the urine. The plasma concentration curve after oral administration in most patients exhibited two maxima, with peak concentrations appearing between 45 and 210 min after dosing.
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    European journal of clinical pharmacology 25 (1983), S. 689-693 
    ISSN: 1432-1041
    Keywords: amiodarone ; bioavailability ; calculation ; linear pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Methods for estimating the bioavailability of drugs with long elimination half-lives are examined. Provided both absorption and disposition are linear a simple linear regression method is developed which can be used to calculate bioavailability in situations where only an incomplete estimate of the area under the curve (AUC) is available. The regression method and the traditional method of comparing the AUC following an oral dose to the AUC following an i.v. dose were applied to simulated data. It was found that the AUC ratio method works well as long as absorption is complete within the time over which the AUC is computed. The regression method is less precise than the AUC ratio method but is more accurate for drugs with long absorption half-lives. When applied to published data on a beta blocker the two methods produced comparable results. The bioavailability of amiodarone in three human subjects was calculated to be 0.20, 0.44 and 0.98 using the regression method with similar results from the ratio method. It is not possible to estimate the clearance of amiodarone from single dose data.
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  • 92
    ISSN: 1432-1041
    Keywords: chlorambucil ; prednimustine ; plasma concentrations ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlorambucil has been investigated in a cross over study after oral administration of the free drug (10 mg) and its prednisolone ester (prednimustine, 100 mg). The bioavailability of chlorambucil was about five times lower when given as prednimustine as compared to administration of the free drug. The peak plasma concentration was about twice as high and it was obtained more rapidly when the free drug was given. No intact prednimustine could be detected in plasma.
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  • 93
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    European journal of clinical pharmacology 24 (1983), S. 563-568 
    ISSN: 1432-1041
    Keywords: indomethacin ; multi-dose kinetics ; controlled release formulation ; capsule formulation ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a controlled release (CR) formulation of indomethacin 75 mg (Indocid-Retard®) given once daily was compared with a conventional 25 mg indomethacin capsule (Indocid®) given 3 times daily for 7 days, to 14 healthy volunteers, using a randomized, cross-over, multiple-dose study design. The following differences in plasma indomethacin profiles after the 2 treatments were observed: average peak concentrations (Cmax) for the CR regimen were higher and the time to peak (Tmax) was significantly delayed. Trough (pre-morning dose) plasma concentrations (Cmin) on Days 2, 5, 6 and 7 were significantly lower after the CR-formulation. No statistically significant differences between preparations for area under the plasma concentration time curve (AUC0–24h) or for renal clearance were observed. Average steady-state plasma concentrations (C p ss ) on Day 7 of the multiple dose regimens averaged 0.477 and 0.427 µg/ml for the 75 mg CR once daily and the conventional 25 mg t.i.d. treatments, respectively. These results show that the bioavailability of the CR and conventional indomethacin formulations under these multiple-dose conditions was not significantly different.
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  • 94
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    European journal of clinical pharmacology 24 (1983), S. 537-542 
    ISSN: 1432-1041
    Keywords: morphine ; analgesic activity ; tablets solution ; pharmacokinetics ; bioavailability ; pain score ; dose-response relationship ; chronic pain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady-state kinetics of morphine given as tablets and solution were compared in 7 cancer patients with chronic pain. There was no accumulation of morphine (20–40 mg) when repeatedly administered every 4 to 6 h. The mean steady-state concentration of morphine during the dose interval varied between 5.9 and 68.4 ng/ml (20.7–240 nmol/l), and was linearly related to the daily dose of morphine. There were no significant differences between the tablets and the solution of morphine with regard to relative oral bioavailability or peak concentration. The time-to-maximum plasma concentrations was significantly longer for the tablets. The pain score profile, assessed by a visual analogue scale during a dose interval, showed a similar pattern after the two oral formulations of morphine. No significant linear relationship between the scores and the plasma concentrations of morphine was observed.
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  • 95
    ISSN: 1432-1041
    Keywords: metoprolol ; bioavailability ; young ; elderly ; metoclopramide ; probanthine ; gut motility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of metoprolol was studied in eight healthy young and seven healthy elderly volunteers. Large interindividual differences in the bioavailability of metoprolol were observed in both groups. However, there was no significant difference in AUC, peak plasma concentration or elimination half-life between young and elderly, but time to peak concentration was significantly longer in the elderly. Pretreatment with metoclopramide had no effect on AUC but caused significant increases in peak concentration and decreases in time to peak concentration in both groups. Probanthine pretreatment (only to the young) resulted in a significant decrease in peak concentration of metoprolol and a significant increase in time to peak concentration but had no effect on the AUC. These results suggest that alterations in gastric emptying and gut motility due to ageing or other drugs have no effect on the overall availability of metoprolol to the systemic circulation but may have significant effects on the time to peak plasma concentration and peak concentration achieved after a single oral dose.
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  • 96
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    European journal of clinical pharmacology 25 (1983), S. 419-424 
    ISSN: 1432-1041
    Keywords: dihydrocodeine ; pharmacokinetics ; acid metabolites ; radioimmunoassay ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum concentrations of dihydrocodeine and its acid metabolites have been determined in seven human volunteers (6 male) who received the drug orally (30 mg and 60 mg) and intravenously (30 mg) on separate occasions, and in twenty-four patients (12 male) receiving 25 mg or 50 mg of the drug intravenously. The concentrations were estimated by radioimmunoassay on reconstituted extracts from serum after an extraction process which effectively separates dihydrocodeine from its polar acidic metabolites. The intravenous data show that dihydrocodeine kinetics followed a two-compartment distribution model. The concentration curves after oral administration indicated relatively rapid absorption with mean peak concentrations at 1.6h–1.8h. The mean half-lives varied between 3.3h–4.5h. From the AUC, the mean bioavailability of orally administered drug was 21% (range 12–34%). The peak levels of the acidic metabolites occurred between 1.8h–2.0h after oral administration and 2.2h–2.5h after i.v. administration, and they were significantly greater after oral administration. The low bioavailability of dihydrocodeine, together with the earlier and higher plasma levels of the acid metabolites after oral administration is suggestive of substantial first-pass metabolism.
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  • 97
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    European journal of clinical pharmacology 25 (1983), S. 467-473 
    ISSN: 1432-1041
    Keywords: hydralazine ; heart failure ; pharmacokinetics ; bioavailability ; metabolism ; hypertension ; dapsone ; acetylator phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of various disease states, other than hypertension, on the pharmacokinetic behaviour of hydralazine is not completely known. In the present study the pharmacokinetics of oral hydralazine has been evaluated in 7 patients with severe, chronic heart failure, using 8 compensated hypertensives as controls. The pharmacokinetics was evaluated by measuring the plasma concentrations of hydralazine (“apparent” and “real” hydralazine) and hydralazine pyruvate hydrazone, and by assessing acetylator phenotype after a small dose of dapsone. The AUC (area under the plasma concentration curve) following a single, oral 50 mg dose was significantly larger in patients with chronic heart failure NYHA Class III–IV than in patients with essential hypertension without cardiac decompensation. A decreased rate of hepatic elimination of hydralazine is suggested as a major contributory factor to this finding.
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  • 98
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    European journal of clinical pharmacology 25 (1983), S. 553-556 
    ISSN: 1432-1041
    Keywords: Endralazine ; pharmacokinetic ; acetylator phenotype ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Endralazine (E), a new hydralazine-like antihypertensive was given intravenously (0.05 mg/kg) to 10 normal volunteers (5 slow and 5 fast acetylators). Plasma levels were fitted to a 3 compartment model and pharmacokinetic parameters (area under curve [AUC 0 ∞ ], clearance, volume of distribution, half-lives) obtained in the usual way. Bioavailabilities of 5 and 10 mg oral doses of E were determined from the AUC 0 ∞ generated in a previous study of oral E given to the same subjects. E had high system bioavailability (73.5–99.1%) suggesting that it was almost completely absorbed without undergoing appreciable first-pass metabolism. Furthermore, dose size and acetylator phenotype did not significantly affect the bioavailability of E. This behaviour contrasts with that of hydralazine where systemic bioavailability was 〈40%, and 2 to 3 times higher in slow acetylators than in fast acetylators. It is concluded that the bioavailability of E is high and not influenced by acetylator phenotype; these properties suggest some clinical advantages for the drug.
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  • 99
    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; children ; sustained-release ; diurnal ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absolute oral bioavailability of a sustained release theophylline tablet (Nuelin-SR250), given 12 hourly was determined in 14 asthmatic children aged 5 to 13 years. In 4 of the patients, mean bioavailability of the fourth dose was 38.9±8.4% and that of the sixth dose was 67.9±25.9% (p〈0.05) in the other ten patients. This suggests steady-state had not been achieved after four doses. In the initial study with 9 patients, a significant diurnal variation in predose plasma theophylline concentrations was observed, as the mean morning predose concentrations were 2.9 fold greater than the mean evening predose concentrations (p〈0.005). Dual peak plasma concentrations occurred in 5 out of the 9 patients. The mechanism of this diurnal variation was investigated in a further 5 asthmatic children (10.8 years ±1.6). Morning and night steady-state plasma theophylline concentrations during a continuous intravenous infusion of aminophylline were not different (14.9±5.3 mg/l vs. 15.6±5.9 mg/l), demonstrating that there was no diurnal variation in the plasma clearance of theophylline. The diurnal variation in predose concentrations with Neulin-SR250 was confirmed with the morning concentrations again being 2.6 fold greater than those in the evening. However, bioavailability was not significantly different for day (09.00–21.00) and night (21.00–09.00) dosing intervals after doses 6 and 7 respectively of Nuelin-SR250. The plasma concentration versus time profiles suggested that the diurnal variation in predose concentrations was due to slower absorption of the evening dose.
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  • 100
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    European journal of clinical pharmacology 24 (1983), S. 509-515 
    ISSN: 1432-1041
    Keywords: cibenzoline ; pharmacokinetics ; bioavailability ; urinary excretion ; antiarrhythmic drug ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of cibenzoline (UP 339.01), a new antiarrhythmic drug, was studied after i.v. and oral administration to 5 healthy subjects. Cibenzoline levels in plasma and urine cibenzoline were measured by a GLC method. After i.v. administration, the total clearance was 826 ml · min−1. The fraction of cibenzoline excreted unchanged in the urine was 0.602 and it was correlated with the creatinine clearance. After i.v. and oral administration, the renal clearances were 499 ml · min−1 and 439 ml · min−1, and the half-lives were 4 h 01 min and 3 h 24 min, respectively. The differences were not significant. Availability by the oral route was 0.92, the maximum plasma concentration being observed at 1 h 36 min. The results were compared with those for other antiarrhythmic drugs.
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