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  • pharmacokinetics  (182)
  • 42.55  (64)
  • Springer  (246)
  • Frontiers Media
  • Springer Nature
  • 2015-2019
  • 1975-1979  (246)
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  • Springer  (246)
  • Frontiers Media
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  • 1
    ISSN: 1432-0630
    Keywords: 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Lasing in atomic lines of noble gases and fluorine, prior to excimer radiation, was observed in an electric discharge ArF/XeF excimer laser. Some Ar/Xe lines end at metastable levels, which are very important for the formation of ArF/XeF excimer molecules. Five new lasing lines of atomic fluorine have been obtained. Consideration is given to the use of lasing in atomic and molecular lines, that occurs in one burst, in investigations of the excitation kinetics of excimer states under the conditions of a high-pressure electric discharge.
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  • 2
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    Applied physics 14 (1977), S. 277-282 
    ISSN: 1432-0630
    Keywords: 42.55 ; 52
    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 paper deals with the properties andI-V characteristics of discharges in narrow capillaries used, for example, for He−Ne waveguide lasers. It has been observed that discharges in He−Ne waveguide lasers are unstable because of the strongly falling characteristic. A theory is presented which assumes that at low currents wall charges restrict the positive column to a narrow plasma channel and are the main reason for the observed falling characteristic. A numerical evaluation for helium gives results which agree well with experimental data.
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  • 3
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    Applied physics 18 (1979), S. 333-338 
    ISSN: 1432-0630
    Keywords: 87 ; 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Energy transfer in DNA-dye-complexes after excitation in the UV down to 220 nm by means of a tunable laser was investigated. DNA of different base composition and polynucleotides were compared. The dyes proflavine, acridine orange and ethidium bromide were used. The energy transfer from DNA-bases to dye molecules was measured in dependence of the excitation wavelength and the base composition of the DNA. Models of the energy transfer from DNA to dye and of the molecular structures of the DNA-dye-complex (intercalation) could be deduced.
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  • 4
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    Applied physics 19 (1979), S. 47-51 
    ISSN: 1432-0630
    Keywords: 42.55 ; 42.80
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The possibility of building free-electron lasers and masers with quasi-circular undulators is considered. The two-mirror cavity is replaced by a suitable waveguide. The magnetic field along the orbit has a continuous component superimposed on the alternating one. Besides allowing large freedom for electron guiding and focusing, the structure allows effective negative mass conditions, which may enhance the electron beam modulation when space charge effect are important. Furthermore the radiation frequency can be higher than that in a linear undulator with the same electron energy, and long interaction times are possible in a compact structure.
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  • 5
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    Applied physics 19 (1979), S. 345-351 
    ISSN: 1432-0630
    Keywords: 78.55 ; 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract PrP5O14, PrxLa1−xP5O14, and PrxY1−xP5O14 (0≦x≦1) single crystals of laser quality were synthesized and their crystallographic and optical parameters measured. Laser emissions in the visible (λ=637.4 nm) with no mirrors in place (superradiance) and also in various optical resonators have been observed.
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  • 6
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    Applied physics 13 (1977), S. 97-99 
    ISSN: 1432-0630
    Keywords: 42.55 ; 82.50
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract First cw laser oscillation with thresholds below 1 mW was observed for various B1Пu → X1 ∑ g + transitions of diatomic molecular sodium excited by different argon laser lines in the range of 454–488 nm. For pump powers of 0.5 W output powers up to 3 mW and single-pass gain up to 0.1 cm−1 were obtained. Some properties of the heat pipe laser system are discussed.
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  • 7
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    Applied physics 13 (1977), S. 383-385 
    ISSN: 1432-0630
    Keywords: 42.55 ; 42.80
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract An optically pumped FIR laser was operated with a copper mesh Fabr-Perot output coupler. With this device a Gaussian output beam was obtained andthe degree of coupling could be varied continuously, thus allowing optimum coupling. From the measured properties of the wire mesches grains of two FIR laser lines are calculated and the saturation intensities estimated.
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  • 8
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    Applied physics 14 (1977), S. 25-28 
    ISSN: 1432-0630
    Keywords: 42.55 ; 42.80
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract A new device for magnetically displacing the output mirror of a laser resonator and synchronously tilting an etalon in order to obtain single-mode tuning of a dye laser over a tuning range of at least 10 GHz is described. Comparatively large displacements with good linearity of a coil mounted on a membrane and placed inside the strong magnetic field of a ring magnet are obtained for currents in the order of several hundred milliamperes. Together with etalon flats of appropriate thickness and reflection mounted in the resonator of the laser a versatile instrument for application in intra and extra cavity spectroscopy has been developed.
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  • 9
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    Applied physics 14 (1977), S. 393-398 
    ISSN: 1432-0630
    Keywords: 34 ; 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract A flowing afterglow method has been used to study a number of reactions of importance in KrF lasers using NF3 as the fluorine donor. Total rate constants are reported for Kr*(3 P 2)+NF3 and Kr++NF3. The thermal energy attachment coefficient has been measured for NF3 and the cross section for the electron excitation process Kr*(3 P 2) +e→Kr*(3 P 1)+e has been estimated. The relevance of these results to discharge pumped KrF lasers is discussed.
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  • 10
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    Applied physics 14 (1977), S. 193-197 
    ISSN: 1432-0630
    Keywords: 42.55 ; 52
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Planar and cylindrical discharges for argon lasers are compared by plasmatheoretical calculations. The maximum laser output power available in the two arrangements is computed in dependence of various parameters neglecting saturation mechanisms. A transverse discharge arrangement confining the positive column by two parallel walls is described and experimental laser threshold values for the current and pressure are reported.
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  • 11
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    Applied physics 14 (1977), S. 255-268 
    ISSN: 1432-0630
    Keywords: 42.80 ; 42.55 ; 85.60
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract GaAs double heterostructure semiconductor injection lasers which now exhibit more than 25000 h cw room temperature lifetime are of great interest for future use as directly modulated transmitters for high bit-rate fiber optical communications. The effects limiting this application are modulation distortions, spectral width and additional spectral broadening in the case of modulation and spontaneous fluctuations of the output power. The dynamic and spectral behavior of injection lasers, the methods of high bit-rate modulation and the improvement of the high bit-rate modulation capability by coupling two lasers are discussed.
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  • 12
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    Applied physics 15 (1978), S. 185-190 
    ISSN: 1432-0630
    Keywords: 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Electron energy loss studies of POPOP andp-terphenyl in the vapor phase at an incident electron energy of 25 eV have been performed. The spectra covering an energy loss between 0 and 9 eV revealed a considerable initial triplet population under electron impact excitation. The implications for electron-beam pumped vapor phase dye lasers are discussed.
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  • 13
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    Applied physics 15 (1978), S. 229-232 
    ISSN: 1432-0630
    Keywords: 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract A new type of discharge tube for high-power argon-ion lasers constructed of a segmented metal-ceramic compound system is described. Up to date, the system has been operating for 1500 h without failure. The maximum cw output is 140 W, limited by the destruction of the mirrors.
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  • 14
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    Applied physics 15 (1978), S. 439-450 
    ISSN: 1432-0630
    Keywords: 42.55 ; 42.65
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract A theoretical model for the ultrashort-pulse (USP) generation by lasers with saturable absorbers is presented. The gain medium is assumed to be a two-level system whereas the absorber is described by a four-level system which is characterized by a two-stage absorption process and the pertinent relaxation times. Laser dynamical equations are developed in the rate-equation approximation and boundary conditions appropriate for an unidirectional ring cavity are established. Evolution of USP is investigated for different combinations of parameter values appropriate for solid-state laser systems by computer simulation, employing a finite difference approximation for the dynamical equations. It is shown that USP output is attainable even if the cross-section of the excited-state absorption isgreater than that of the ground-state absorption and the laser is operating just above threshold. In fact, it is found that through the participation of a strong excited-state absorption the discrimination against satellite pulses is enhanced so that single-pulse output is more achievable. Furthermore, it is proposed that single picosecond pulses may be obtainable from relatively broad initial peaks by utilizing the high pulse-selection and pulse-shortening efficiency of the absorber due to the contribution of the excited-state absorption. The applicability of the present model to singlet-triplet crossing and photoisomer formation is also discussed.
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  • 15
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    Applied physics 16 (1978), S. 297-301 
    ISSN: 1432-0630
    Keywords: 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract A grating-tuned cw dye laser with an emission bandwidth of less than 1 GHz and output power in excess of 400 mW has been constructed. This was accomplished using a newly developed holographic grating with sinusoidal groove profile, which resulted in an enhanced spectral efficiency up to 94%. The low losses and the broad spectral working range (more than 1000 Å) which can be easily covered by simple rotation make these gratings an attractive single-stage tuning element for low-gain cw lasers.
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  • 16
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    Applied physics 16 (1978), S. 151-154 
    ISSN: 1432-0630
    Keywords: 42.65 ; 42.55 ; 33
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract We observed tunable UV radiation down to 175 nm by SRS of the output of a frequency-doubled dye laser in H2. The high power output of the 4th anti-Stokes to 5th Stokes line generated by the frequency doubled dye laser and the 8th anti-Stokes to 3rd Stokes line generated by the undoubled dye laser represents a broadly tunable coherent radiation source between 189 nm and 2064 nm.
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  • 17
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    Applied physics 13 (1977), S. 109-110 
    ISSN: 1432-0630
    Keywords: 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract A simple technique is described that allows the generation of a short pulses (1 ns) from dye lasers pumped by a much longer (7 ns) N2-laser pulse. Dye-laser pulses, either with a narrow bandwidth or a short duration, can thus be obtained with the same N2-laser pump.
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  • 18
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    Applied physics 17 (1978), S. 367-370 
    ISSN: 1432-0630
    Keywords: 42.55 ; 78.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract We report on room temperature quasi-cw laser action in K5Nd(MoO4)4 at a wavelength of 1.067 μm. The crystal was pumped with the 5140 Å line of an argon ion laser. Due to thermal effects actual cw lasing was not possible. Chopping the pump light with a low duty cycle of 1∶1000 leads to quasi-cw laser action and stable output power. We have determined the fundamental laser parameters: threshold pump powerA T=15 mW, slope efficiency η=22%, and internal lossesL=2.5%. In order to explain the measured relaxation oscillations, diffusion of the excited 4f-excitons is considered. According to a recently developed theory, a diffusion constant ofD=2×10−6cm2/s explains the observed results.
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  • 19
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    Applied physics 14 (1977), S. 121-122 
    ISSN: 1432-0630
    Keywords: 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Frequency-tunable generation by means of F 2 + and F 2 − colour centers in a LiF crystal is reported. Colour centers were created by illuminating LiF crystals with electrons of 3 meV energy at the electron current density of 1 μA/cm2. The pumping source was a ruby laser with a peak power of 20 MW, a pulse duration of 20 ns, and a repetition rate of 1 Hz. The frequency tuning is obtained in the range of 0.88–1.25 μm. Discussed are the ways of pumping of colour centers and the possibility of lasing in the spectral region of 0.85 to 2 μm in the type of colour centers under investigation.
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  • 20
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    Applied physics 18 (1979), S. 257-260 
    ISSN: 1432-0630
    Keywords: 32 ; 42.55
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract We have demonstrated the feasibility of Doppler-free polarization spectroscopy with a train of ultrashort pulses from a synchronously pumped mode-locked dye laser. The sensitivity of the method is compared with saturation spectroscopy with a single-mode laser.
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  • 21
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    Applied physics 15 (1978), S. 191-196 
    ISSN: 1432-0630
    Keywords: 42.55
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    Notes: Abstract A guideline for the optimum design of linear wall-ablation lamps is presented with a simple empirical formula which describes the luminescent characteristics of lamps. The absolute luminescent efficiency of the wall-ablation lamp was measured. A high-energy dye laser with a quadruple-elliptical cylindrical cavity was constructed using these lamps, and an output energy of 23.3 J (11.6 MW) was obtained with an overall efficiency of 0.31 %. The energy-flow diagram of this laser system was computed with a rate-equation analysis, and the conversion efficiency from electrical input to laser output was determined. One can expect an overall efficiency of about 2 %.
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  • 22
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    Applied physics 17 (1978), S. 181-187 
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    Keywords: 42.55
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    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract A complete theoretical model for optically pumped dye lasers is studied using the rate equation approach which includes excited singlet and triplet state absorption effects. Closed-form solutions under steady-state conditions reveal a novel nonlinear threshold phenomenon: partial reabsorption of the excited laser light can lead to a discontinuous onset of laser oscillation above laser threshold. Theoretical and experimental results for a transversely and longitudinally pumped rhodamine 6G laser are presented in terms of softmode and hardmode behavior at threshold.
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  • 23
    ISSN: 1432-0630
    Keywords: 33 ; 42.55
    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 characteristics of a stable, external-resonator spin-flip Raman laser (SFRL), pumped by a cw carbon monoxide laser of controlled mode quality and spectral content, are determined using a combination of molecular spectroscopy, Raman amplifier and confocal Fabry-Perot interferometer measurements, and heterodyne detection. Single-frequency output of a free-running external-resonator is demonstrated with an inherent linewidth of 〈10 kHz and a short-term frequency jitter of ≃100 kHz. With the resonator length actively controlled to lock an axial mode frequency to the peak of the spontaneous gain, the linewidth of the SFRL output was maintained below 2 MHz. In this mode of operation, small variations in the output tuning rate, corresponding to the magnetic field dependence of the conduction-electrong-factor, were calibrated. Molecular absorption spectra obtained using gas cells both inside and outside the resonator have been used to illustrate the high resolution, wide-range tuning capability and sensitivity of the system. Lambda-doubling of the $$^2 \pi _{3/2} $$ of the Q-branch head of nitric oxide was measured for values ofJ down to 13/2, below which the splitting is less than the Doppler width. The splittings agreed with predictions using parameters obtained by conventional spectra for higherJ-values.
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  • 24
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    Applied physics 19 (1979), S. 241-242 
    ISSN: 1432-0630
    Keywords: 33 ; 42.55
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    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Several new laser lines using optically pumped deuterated methanol molecules have been discovered. These not only increase the spectral coverage of pumped methanol isotopes but may assist in the assignment of a molecular structure.
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  • 25
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    Applied physics 19 (1979), S. 399-403 
    ISSN: 1432-0630
    Keywords: 42.55
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    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The selection of a single longitudinal mode of a dye laser can be achieved with double or triple Michelson reflectors instead of Fabry-Perot etalons inside the laser cavity. These systems can be adapted to commercial multimode dye lasers. They provide a high efficiency and a good geometrical quality of the output beam. With a 7 watt pump power (λ=514.5 nm line of the Ar+ laser), a tunable output power of 1 watt was obtained at the peak of R6G, in the main output beam; the total single-mode power, including the auxiliary output beams, exceeded 1.4 watt. These results correspond to efficiencies of 14% and 20%, respectively (24% and 30% slope efficiencies). We discuss in the text why these efficiencies are comparable to those of ring lasers. In the infrared, with a 4.5 watt pump power (red lines of a Kr+ laser), 250 mW of single-mode output power in the main output beam was obtained at 780 nm with Oxazine 750.
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  • 26
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    Applied physics 19 (1979), S. 427-429 
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    Keywords: 33 ; 35 ; 42.55
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    Notes: Abstract Spectral coincidences between CO-laser lines and NO fundamental absorption lines were reinvestigated in order to resolve discrepancies between recently published papers. The absorption of CO laser radiation by NO and NO/Ar mixtures was measured and fitted by calculations using a Voigt profile for the NO line shapes. A new coincidence with a frequency offset of less than the NO Doppler width was found.
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  • 27
    ISSN: 1432-0630
    Keywords: 07 ; 42.55
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    Notes: Abstract A liquid-nitrogen cooled12C16O laser was operated both Q-switched and cw. A total of 276 lasing transitions were observed in cw using an intracavity grating for line selection. In the Q-switch mode, 230 lines occurred without dispersive element in the cavity.
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  • 28
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    Applied physics 18 (1979), S. 235-241 
    ISSN: 1432-0630
    Keywords: 42.65C ; 42.55 ; 33.20
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    Notes: Abstract Design and performance characteristics of a tunable ir waveguide Raman laser pumped by a high power dye laser are described. Using SRS up to third Stokes order in compressed H2, the wavelength range from 0.7 to 7 μm has been covered without gaps. Taking advantage of a waveguide structure in the scattering chamber, energy conversion efficiencies better than 1% with power levels in excess of 80 kW for the third Stokes component have been achieved. The experimental results support the theoretical predictions that a 4-wave parametric process is responsible for the production of the third Stokes component.
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  • 29
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    Applied physics 20 (1979), S. 41-50 
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    Keywords: 41 ; 42.55 ; 95
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    Notes: Abstract The interaction of free electrons and free electromagnetic radiation, in the presence of a uniform magnetic field, can result in stimulated emission or absorption. We analyze the dynamics of single electrons by solving the classical, relativistic Lorentz force equations of motion in these combined fields. An electron may gain energy from, or lose energy to, the radiation field, depending crucially on the phase and oscillation frequency of the electron's helical motion within the superposed, circularly polarized light wave. To first order in the radiation field strength, electrons in a monoenergetic, uniformly distributed beam become spatially bunched, but there is no net energy change. To second order, however, the beam may experience a gain or loss of energy, corresponding to attenuation or amplification of radiation. We compare the bunching of this laser process to the bunching processes involved in 1) the Stanford free-electron laser and 2) the cyclotron maser, and find significant differences in each case. Our analytic results provide a clear, simple picture of the interaction process, and can be useful in exploring light amplification in astrophysical magnetic fields, the magnetosphere, or in laboratory devices.
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  • 30
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    Applied physics 20 (1979), S. 61-65 
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    Notes: Abstract We show that a laser can efficiently accelerate charged particles if a magnetic field is introduced to improve the coupling between the particle and the wave. Solving the relativistic equations of motion for an electron in a uniform magnetic field and superposed, circularly polarized electromagnetic wave, we find that in energy-position phase space an electron traces out a curtate cycloid: it alternately gains and loses energy. If, however, the parameters are chosen so that the electron's oscillations in the two fields are resonant, it will continually accelerate or decelerate depending on its initial position within a wavelength of light. A laboratory accelerator operating under these resonant conditions appears attractive: in a magnetic field of 105 Gauss, and the fields of a 5×1012 W, 10 μm wavelength laser, an optimally positioned electron would accelerate to 700 MeV in only 10m.
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  • 31
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    Applied physics 20 (1979), S. 97-99 
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    Notes: Abstract A narrow-band tunable double-wavelength dye laser with a bandwidth of 0.1 cm−1 is described. The output at one of the wavelengths is found to be completely linearly polarized in the plane of incidence.
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  • 32
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    Applied physics 13 (1977), S. 107-108 
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    Notes: Abstract Intense laser oscillation has been observed from ArF molecules at 1933 Å. Excitation of the gas mixture NF3:Ar:He=1:55:630 at total pressures above 2.1 atm was produced by a transverse electric discharge. The range of fine tuning was from 1927 Å to 1936 Å. An output energy of 0.8 mJ was measured from a laser pulse 15 ns in duration.
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  • 33
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    Applied physics 17 (1978), S. 257-267 
    ISSN: 1432-0630
    Keywords: 42.55 ; 32.60
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    Notes: Abstract The effect of transversally applied magnetic fields on the polarization behavior of a single-mode gas laser is theoretically investigated, stressing the importance of the additivity of respective contributions influencing the time evolution of polarization parameters. By adding a new element to the existing theory, namely the contribution of magnetic-field-free regions in the active medium, and by considering the relatively large effects that small cavity anisotropies can cause, several apparent discrepancies between experiments and existing theory are resolved.
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    Applied physics 15 (1978), S. 59-63 
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    Notes: Abstract Feedback controlled self-excitation of optical pulses of nanosecond duration has been observed to occur rather reliably in a CW dye ring laser, oscillating in a traveling mode. These observations are described analytically by means of a direct time domain approach. It is shown that a steady-state Gaussian pulse whose time duration determined from the self consistency condition in terms of system characteristics describes accurately the observed pulse behaviors.
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  • 35
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    Applied physics 19 (1979), S. 39-41 
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    Notes: Abstract It is shown that when a distributed feedback dye laser is used to generate a train of picosecond pulses, the narrow lines observed in the spectrum are not longitudinal modes, but are due to the intrapulse refractive index changes caused by the heating effect of the pumping pulse.
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  • 36
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    Applied physics 18 (1979), S. 415-419 
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    Notes: Abstract Remarkable intensity fluctuations were observed in the LiNdP4O12 (LNP) laser by placing a moving ground-glass plate across the ouput beam. Resonance-like behaviors were also observed by tuning the moving velocity of the ground-glass plate, with respect to relaxation oscillations. Classical rate equations including the modulation term were given to explain the observed phenomena. Similar intensity fluctuations corresponding to relaxation oscillations were observed when the LNP laser light beam was coupled to an optical fiber.
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  • 37
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    Applied physics 19 (1979), S. 35-37 
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    Notes: Abstract Results of an investigation of 19 organic dyes pumped by a 1.7 MW discharge-pumped XeCl excimer laser are reported. The dye-laser emission covered a wide wavelength range from 340 nm to 710 nm.P-terphenyl shows efficient laser action. The highest energy conversion efficiency exceeds 40% in visible region. In comparison with 250 kW nitrogen laser pumping, higher efficiencies are obtained for most of these dyes in the same dye-laser configuration.
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  • 38
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    Applied physics 19 (1979), S. 185-189 
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    Notes: Abstract We have studied the interaction of stimulated spin-flip Raman scattering and stimulated recombination radiation in n-InSb using a CW CO pump laser. A change in linewidth and output power of second Stokes spin-flip radiation is observed when the tuning curve of the first Stokes stimulated spin-flip radiation and the stimulated recombination radiation cross. The observations are explained using a simple rate equation model.
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  • 39
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    Applied physics 18 (1979), S. 77-80 
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    Notes: Abstract We report, for the first time, on room temperature cw laser action of NdP5O14 and NdAl3(BO3)4 at 1.3 μm wavelength. The emission cross sections of the transition4 F 3/2→4 I 13/2 are 0.24·10−19 cm2 and 1.74·10−19 cm2, respectively. The lowest observed threshold was 45 mW and the slope efficiency was nearly 10%. The minimum threshold is expected to be about 5 mW of absorbed pump light for both materials.
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  • 40
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    Notes: Abstract Laser induced nonlinear absorption profiles in a three-level system have been recorded to study the effect of elastic collisions upon optical coherences. In our particular system, the signal is due to a pure double-quantum term, where we have separated the effect of phase-interrupting collisions from the effect of velocity-changing collisions. Experimental results show that the effect of velocity-changing collisions is very small, and that broadening of the signal is due to phase-interrupting collisions mainly. We are able to determine the increase of the decay rate of the coherent superposition (the “coherence”) of two levels of same parity [Dγ 13/dp=(6.5±1) MHz/Torr] and an upper limit for the mean velocity change (ũ≲5m/s).
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  • 41
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    Applied physics 19 (1979), S. 165-170 
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    Notes: Abstract Computer calculations of ETDL performance indicate that dye laser output can be manipulated by an appropriate choice of a donor (absorber)-acceptor (dye) couple. Studies of relevant laser induced inter- and intramolecular energy transfer processes are presented.
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  • 42
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    Applied physics 19 (1979), S. 221-224 
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    Keywords: 42.10 ; 42.55 ; 42.65
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    Notes: Abstract Wave front of a light pulse is shown to be unstable as it propagates through a resonant saturable absorber, if its frequency is higher than the resonance frequency of the absorber. When ΔωT 2∼1, a small-scale transverse instability with the dimension of (λl abs)1/2 grows rapidly. Its growth-rate is of the order of the small-signal-absorption length of the medium.
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  • 43
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    Applied physics 19 (1979), S. 257-264 
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    Notes: Abstract Employing injection-locking techniques an oscillator configuration was found comprising in a simple way all the features required for fusion directed high-power CO2 laser systems. The oscillator provides emission in single axial modes on rotational transitions which can be freely selected by feeding fluencies of a few mW/cm2 at the particular transition into the oscillator cavity. In the same way simultaneous emission on selectable lines can be achieved. By the same principle the oscillator can be forced to emit in any orientation of polarization. The set up is relatively simple, the alignment rather uncritical, and the operation reliable. Gaussian-shaped nanosecond pulses with low forepulse power are produced with the help of a pulse cutter and saturable multiline absorber. The set up is described and its features are demonstrated by measurements.
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  • 44
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    Applied physics 13 (1977), S. 1-3 
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    Notes: Abstract Disappearance of NF3 and appearance of NF2 and N2F2 in an excimer laser is followed quantitatively with a mass spectrometer. A model for the kinetics is presented.
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  • 45
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    Applied physics 13 (1977), S. 55-58 
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    Notes: Abstract NdxLa1−xP5O14 (0.25≦x≦1) single crystals, placed within a confocal optical resonator, were pumped with ruby laser fundamental and second-harmonic nanosecond pulses. In both cases laser oscillations at 1.05 μm exceeding in duration many times the pumping pulse were obtained.
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  • 46
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    Applied physics 14 (1977), S. 343-350 
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    Notes: Abstract By means of nonlinear absorption spectroscopy data necessary for the interpretation of molecular spectra can be obtained in such spectral regions, where conventional spectroscopic methods yield only a quasi-continuous absorption curve. Using a Zeeman-tuned He−Ne laser at the wavelength of 3.39μm we have measured significant differences in the intensity and temperature behaviour for several ethane absorption lines, the analysis of which made possible a preliminary qualitative assignment of these lines.
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  • 47
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    Applied physics 14 (1977), S. 377-380 
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    Notes: Abstract Due to spatial hole burning, standing-wave dye lasers require a large amount of selectivity inside the cavity for single-mode operation. The output power of these lasers is limited by losses caused by the frequency selecting elements. In a travelling-wave laser, on the other hand, spatial hole burning does not exist, thereby eliminating the need for high selectivity. A travelling-wave cw dye laser was realized by unidirectional operation of a ring laser, yielding single mode output powers of 1.2 W at 595 nm and of 55 mW in the UV-region with intracavity frequency doubling.
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  • 48
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    Applied physics 15 (1978), S. 265-270 
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    Notes: Abstract For a homogeneously broadened two-level ring laser model the stability of the cw laser oscillation in the presence of a passive medium is investigated. The passive material is treated similar to the active material, but without an external pumping mechanism. Stable and unstable regions are shown for various parameters. The stability region of the cw solution becomes extremly small for certain parameters.
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  • 49
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    Applied physics 16 (1978), S. 155-158 
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    Keywords: 42.55 ; 78.60 ; 85.60
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    Notes: Abstract Dynamic characteristics of laser diodes are numerically calculated on multi-mode rate equations, including spatial relaxing interaction causing mode competitions or jumps. It is revealed that the interaction effect is classified into three cases [“independent (or inhomogeneous)”, “competition (or intermediate)”, and “monopoly (or ideally homogeneous)”], that an optimum relaxing coefficient value exists to minimize relaxation oscillations in rise and decay transients, and that the optimum value is related to the relaxation period. Calculated results are discussed in comparison with the experimental results.
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    Notes: Abstract The room temperature cw oscillation at 1.05 and 1.32 μm of lithium neodymium tetraphosphate [LiNd(PO3)4, LNP] lasers in an external resonator and, for the first time, also in a Fabry-Perot resonator with directly applied mirrors is reported. The growth and fluorescence properties of the LNP crystals are briefly described. Laser parameters such as threshold pump power, output power, differential efficiency, optical gain, emission cross section and laser modes are both measured and calculated. Laser experiments show the threshold pump power to be lower for 1.05 μm than for 1.32 μm emission because of the smaller emission cross section; the pump power density is lower for the external resonator than for the Fabry-Perot resonator because of its higher mode losses.
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    Applied physics 14 (1977), S. 199-203 
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    Keywords: 42.55 ; 82.50
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    Notes: Abstract Loss of gain in a dye medium as a result of decomposition by pump photons is considered in terms of disappearance of dye molecules and the appearance of a new, single chemical product having absorption in the fluorescence band. The cases of small signal gain and saturated gain are applied to a single pass through a transversely excited amplifier. Loss of output, defined as “quantum yield of laser deterioration”,Q L , is related to the true quantum yield of molecular destruction of the dye,Q M , and other known parameters. For the experimentally common, saturated gain condition, the smallestQ L can be isQ M , which requires a photochemically bleachable dye with high gain, preferably at high concentration, in a long cavity, operating at high injection and pumping fluxes. Reversing these conditions, the highest valueQ L can be, compared withQ M , is unrestricted.
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  • 52
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    Applied physics 17 (1978), S. 303-307 
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    Notes: Abstract A new and simple technique for measuring the effective diameter of a laser beam used in material processing is described. The time for the temperature of a spot heated by the laser beam to rise to 90% of equilibrium is compared with that predicted theoretically for a Gaussian TEM00 laser beam. A Gaussian beam diameter equivalent is thus deduced. This calculated diameter is of particular relevance to applications where the laser is used as a heat source.
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    Applied physics 17 (1978), S. 393-400 
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    Notes: Abstract Stimulated Raman scattering by polaritons when employing a nonlinear crystal inside the cavity of the laser with Q-switching and locked to fundamental frequency was theoretically studied. The equations were formulated describing the dynamics of the fundamental, Stokes and polariton waves under the assumption of instant Q-switching and uniformity of radiation except in the longitudinal direction. Numerical solutions of the equations were found and analysed. We demonstrate the influence, on generation characteristics, of the most important parameters, such as the effective nonlinearity, the initial level of population inversion, the feedback of the Stokes wave and the group mismatch between a Stokes and a pump wave. Optimum generation conditions are determined. Possibilities of the method are discussed for the generation of a) giant pulses which are controllable with regard to carrier frequency and duration but are unachievable with other methods, b) Stokes pulses of very small duration and high energy having sharp trailing edges, and c) analogous polariton pulses in the middle and far infrared range. The generation using a number of polariton branches in LiNbO3 was considered as an example. Calculations are in qualitative agreement with experimental data.
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    Applied physics 17 (1978), S. 211-232 
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    Notes: Abstract Physical principles, new ways and means of creation, schemes, characteristics and features of efficient high-power tunable pulse Raman lasers, operating in the near and middle ir are reviewed. The paper includes: tunable dye and Nd lasers as pump sources; promising active media and their optimal excitation methods; optical systems for producing spatially homogeneous pumping; the physics of Raman oscillators and their practical schemes, efficient high pulse energy liquid N2 and compressed H2 Raman oscillators, covering several bands in the range between 1.4 and 9.2 μm; the physics and construction of efficient tunable Raman amplifiers-convertors, amplifying in the saturation regime of spontaneously scattered or beforehand produced and collimated external Stokes signals, obtained in the spectral range between 0.83 μm and 18 μm. Raman laser using a, so-called, broadband pump where the linewidth of pumping light is broader than the spontaneous scattering linewidth, are also discussed. Features of both amplification and oscillation regimes of such broadband pumped Raman lasers are reported, and conditions for the efficient frequency conversion are determined.
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    Notes: Abstract Design and operating caracteristics of high pulse repetition rate NH3 laser producing up to 20 W of average output power are described. The NH3 laser, operating in the 12–13 μm region was optically pumped with a high pulse repetition rate TEA CO2 laser. Dependences of the NH3 laser output on the pump energy, ammonia and buffer gas pressures and pulse repetition rate have been studied. The conversion efficiency of up to 16% has been received.
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  • 56
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    Notes: Abstract We report the first accurate measurements of the transition strengths and linewidths of the 00o2 9.4 μm sequence lines of CO2. This sequence band is found to be very similar to the regular 00o1 laser band, except for an experimentally determined factor of 1.89±0.12 increase in transition strength (if the CO2 molecule is treated as a simple harmonic oscillator the theoretical increase in transition strength is 2.0). The laser absorption spectrometer used for these measurements can detect absorption coefficients in CO2 of ≈10−7 m−1, and we discuss the feasibility of using this sensitivity to monitor rare isotopic forms of CO2.
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    Applied physics 19 (1979), S. 243-245 
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    Notes: Abstract Stable step-tunable simultaneous double-wavelength emission from any branch combination of the 9.6 and 10.6 μm bands of a cw CO2 laser is reported in which the relative strengths of the two signals may be controlled.
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    Applied physics 18 (1979), S. 177-181 
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    Keywords: 42.55 ; 42.65 ; 33
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    Notes: Abstract We have studied experimentally stimulated Raman scattering and 4-wave-interaction processes occuring in hydrogen gas, which is excited by a Nd:YAG-pumped dye laser. The tuning ranges of the various Stokes and anti-Stokes lines, which are generated with high efficiency, cover the spectrum from 185 to 880 nm without a gap.
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    Applied physics 20 (1979), S. 129-134 
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    Keywords: 42.55 ; 33 ; 82.50
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    Notes: Abstract Collisional coupling between theB, C, andD states of KrF is measured in a discharge pumped KrF laser. Detection of the time resolved populations in the three states via measurement of the side fluorescence in theB→X, C→A, andD→X bands is used to record the collisional relaxation from theC andD state to theB state during laser emission. The experimentally determined limits for the collisional coupling times are τB-C≦1 ns and τB-D,τC-D〈20 ns at total pressures of 2 bar. Investigation of theB→X fluorescence band shows that the vibrational manifold of theB state is not thermalized during laser emission. TheV-V,T coupling time is estimated to be τV-V,T=4±2 ns. The influence of collisional coupling on energy extraction in the KrF laser is discussed.
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    Notes: Abstract An analytical treatment of the ultrashort-pulse generation in a solid-state laser is given taking into account gain saturation. The probability for the breakdown of the picosecond-pulse evolution caused by the amplification depletion is calculated. The influence of the active medium saturation on the satellite-pulse probability is investigated. Both probabilities characterize the mode-locking behaviour of the laser system and are calculated for various laser parameters to find an optimum laser regime.
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    Applied physics 19 (1979), S. 127-130 
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    Notes: Abstract The possibility of using stimulated emission from the recombination of electron-positron pairs for obtaining coherent γ-rays is considered. The critical number of pairs needed for the process is calculated.
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    Applied physics 19 (1979), S. 359-361 
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    Notes: Abstract This paper describes a 1 m-long CW HCN discharge laser with a hollow dielectric rectangular discharge tube of 5×20 cm2 cross-section. For optimum working conditions, the characteristics of the amplifying medium have been made constant over the cross-section, by using an additional magnetic field. Then, the unsaturated gain for the 337 μm line is 6.8% m−1. It is shown to be dependent on the smaller dimension of the cross-section rather than on the other dimension. By using the tube as a waveguide, laser output power of 1 Watt might be obtained with a discharge length of 4 m, instead of the 12m-long discharge required to get the same output power from a cylindrical waveguide laser.
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    Applied physics 20 (1979), S. 257-259 
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    Notes: Abstract Selective electronic excitation of single kinds of DNA bases were performed with dye lasers. Different DNA-dye-complexes were used and the selective excitation could be proved by the varying strength of the interaction between the bases and the dye molecules.
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    Applied physics 20 (1979), S. 261-264 
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    Notes: Abstract The method of Stimulated Mandelshtam-Brillouin Scattering (SMBS) is utilized in a powerful laser to obtain better transverse beam quality by phase conjugation. The principle is explained, and the conclusions are substantiated by experimental results.
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    European journal of clinical pharmacology 8 (1975), S. 97-105 
    ISSN: 1432-1041
    Keywords: Di-n-propylacetate ; 2-propyl-valeric acid sodium salt ; pharmacokinetics ; anti-epileptic ; drug monitoring ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the anti-epileptic drug di-n-propylacetate (DepakineR) have been studied in 7 patients, in whom plasma concentrations were determined during and following subchronic treatment. Elimination of the drug appeared to follow a monophasic exponential course; biological half lives were 8 to 15 hours. The data supported the assumption that an open one-compartment model can be used to describe the kinetics of dipropylacetate in man. The drug appeared to have a relatively restricted distribution: calculated relative distribution volumes ranged from 0.15 to 0.40 1/kg. There were large interindividual differences in clearance rate. The therapeutic range was considered to be between 50 and 100 mg/1 plasma. Plasma levels of phenobarbital were markedly raised during treatment with dipropylacetate for an unknown reason. Determination of the plasma concentrations of drugs at accurately fixed times appears to be a reliable method for pharmacotherapeutic monitoring of epileptic patients.
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    European journal of clinical pharmacology 8 (1975), S. 157-160 
    ISSN: 1432-1041
    Keywords: Isosorbide dinitrate ; pharmacokinetics ; metabolism ; pharmacological action ; nitrates
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An oral dose of 5 mg of14C-isosorbide dinitrate was rapidly absorbed, biotransformed and excreted by human subjects. Peak whole blood concentrations of radioactivity were reached after 1.5 to 2 hours and declined relatively slowly. The radioactivity in whole blood mainly represented metabolites, isosorbide mononitrates. The peak concentrations found were 4.5, 11.7 and 34.3 ng/ml of isosorbide dinitrate, isosorbide 2-mononitrate and isosorbide 5-mononitrate, respectively, in the blood of one subject and 5.9, 15 and 61.3 ng/ml, respectively, in the blood of another subject. However, concentrations of the metabolites declined relatively slowly during 6 h after the oral dose. Up to 99% of an oral dose of isosorbide dinitrate was excreted during 5 days, mainly in the urine of the first day (ca. 78%). The results showed that isosorbide mononitrates were available to contribute to the pharmacological action.
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    European journal of clinical pharmacology 8 (1975), S. 241-248 
    ISSN: 1432-1041
    Keywords: pharmacokinetics ; experimental design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It is apparent from studying recent articles on pharmacokinetics that a number of misunder-standings exist, both about the design of experiments and the analysis of results. The purpose of this paper is to outline many of the common pitfalls associated with the design of experiments and also the limitations upon the analysis of results. The paper describes mathematical, laboratory and clinical aspects which must be examined in designing a protocol for pharmacokinetic experiments. Simulated data is presented to demonstrate the dangers of using standard computer programs for parameter estimation. Even when convergence is obtained the answers may be dependent on the method employed. A mathematical model is of little use unless a reasonable amount of good, accurate data is obtained.
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  • 68
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    European journal of clinical pharmacology 8 (1975), S. 249-254 
    ISSN: 1432-1041
    Keywords: Clonazepam ; 7-amino-clonazepam ; pharmacokinetics ; side-effects ; man
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects. At a daily dose of 6 mg, the average plasma levels of both substances were about 50ng/ml, and individual values ranged from 30 to about 80ng/ml. There was a linear correlation between changes in dose and the resulting plasma levels, which indicates first order elimination kinetics. Side-effects were frequent, but neither their severity nor their occurrence could be related to plasma levels or to the rate of increase in plasma concentration of the drug. Three out of five patients who developed serious dysphoria had significantly high CNP levels. The concentration of ACNP was considerably increased in four patients who subsequently suffered from withdrawal symptoms. Drug interaction with diphenylhydantoin, i.e. decreased CNP level, was observed in all five patients who received both compounds. In general it is not yet possible to define an upper limit for the plasma levels of CNP and ACNP at which toxicity occurs. In patients treated with conventional doses of CNP, measurement of plasma concentration is not required, except in special circumstances, because of the lack of correlation between plasma level and side-effects.
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  • 69
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    European journal of clinical pharmacology 8 (1975), S. 271-275 
    ISSN: 1432-1041
    Keywords: Fluorophenindione ; vitamin K antagonist ; pharmacokinetics ; loading dose ; anticoagulant
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After administration of a single loading dose (80 mg p.o.) of fluorophenindione, the prothrombin level decreased to 37 % in 24 h, and the effect lasted for 48 h. Accordingly, fluorophenindione can be classified as an anticoagulant with an “intermediate” effect. Its elimination half-life was 31 h, which is longer than that of phenindione, because of the greater stability of the fluorinated derivate.
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  • 70
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    European journal of clinical pharmacology 8 (1975), S. 343-347 
    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; man ; two compartment model
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nortriptyline have been assayed in four subjects after intravenous infusion of 57 mg nortriptyline hydrochloride. The data were evaluated according to a two compartment open model. The calculated best-fitting curves were in good agreement with the experimental data, better than could be expected from a simpler model. This justifies the assumption that the kinetics of nortriptyline in man may be described by this model with an appropriate input function. The data permitted estimation of all the parameters of the model. The meaning of the parameters is discussed, particularly in relation to individual variation.
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  • 71
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    European journal of clinical pharmacology 8 (1975), S. 283-284 
    ISSN: 1432-1041
    Keywords: Newborn infants ; carbamazepine ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma elimination of carbamazepine (Tegretol®) was studied in five newborns who had got the drug transplacentally from their epileptic mothers. The half-lives ranged from 8.2 – 27.7 hours which is comparable or even shorter than those found in adults after a single oral dose, but in the same range as those found in adults after multiple oral doses. This suggests that the newborns' drug metabolizing capacity has been induced during fetal life.
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  • 72
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    European journal of clinical pharmacology 9 (1975), S. 1-8 
    ISSN: 1432-1041
    Keywords: Serum concentrations ; individual drug dosage ; pharmacokinetics ; individual variation
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The importance of individualizing the dosage of potent drugs in order to maximize their therapeutic effectiveness and safety is generally accepted. Whenever possible the dosage of a drug should be “titrated” directly in each patient against the intensity of its therapeutic or toxic actions. Unfortunately, for many drugs convenient clinical yardsticks of the intensity of their pharmacologic effects are lacking. Determination of the serum concentration of such compounds can help to guide adjustment of dosage during their therapeutic use. By measuring the serum level of drugs one bypasses the largest source of individual differences in doseeffect relationships — the pharmacokinetic variation between subjects. However, the relationship between the serum concentration of a drug and the intensity of its pharmacodynamic action is influenced by many other factors, which must always be considered in interpretation of serum levels. Therapeutic decisions should never be based solely on the serum concentration of a compound, nor can such measurements ever substitute for careful medical observation and judgement.
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  • 73
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    European journal of clinical pharmacology 9 (1975), S. 57-61 
    ISSN: 1432-1041
    Keywords: Furosemide ; gastrointestinal absorption ; diuretics ; glucuronides ; pharmacokinetics ; metabolism
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 35S-furosemide was administered orally (n=7) or i.v. (n=2) to healthy subjects. The average gastrointestinal uptake estimated by comparison of the urinary recovery of label and the areas under the plasma curves after the two routes of administration was 65%. The half life of radioactivity in the plasma after oral35S-furosemide was 90 ± 17 min (estimated on the slope between 2 and 6 h); the corresponding figure after35S-furosemide i.v. was 47–53 min (slope 0.5–4 h). There was probably a slower phase after 4–6 h. Fractionation of labelled material in urine from two subjects demonstrated that approximately two thirds of the label recovered at 24 h had the same chromatographic properties as furosemide. A major part of the metabolite(s) was probably furosemide glucuronide. There was no evidence that 4-chloro-5-sulfamoylanthranilic acid was formed in man. The total urinary recovery of label (5–7 d) after oral and intravenous administration was 55.1±3.2 (mean±SD) and 82–84%, respectively. After35S-furosemide i.v., 6–9% of the label was recovered in faeces, and it could not be accounted for solely by biliary excretion of furosemide.
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  • 74
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    Keywords: Pivampicillin ; ampicillin ; probenecid ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty male volunteers received oral doses (2100, 1050, and 525 mg) of a pivampicillin-probenecid salt in a 1 to 1 molar ratio (MK-356) at 12 hour intervals. After each dose peak serum concentrations of probenecid were observed 2 hours later than peak concentrations of ampicillin. Following the first dose of MK-356 the apparent elimination rate of ampicillin was dose-dependent and did not follow first order kinetics, as it showed a longer apparent half life after a higher dose. An equal dose of MK-356 administered 12 hours later caused an increase in the peak serum ampicillin level greater than expected from the concentration of ampicillin after the preceding dose. In twelve male volunteers who received at random 525 mg of MK-356 or 350 mg of pivampicillin, each three times daily for 4 days, the areas under the ampicillin concentration curve were the same after the first or last dose of either drug. When 2100 or 1050 mg of MK-356 was taken as an initial dose, 30 to 40 per cent of the ampicillin was recovered from urine in the ensuing 12 hours. The results indicate that when at least 400 mg probenecid was coadministered twice daily with 700 mg pivampicillin (MK-356), the peak serum concentrations of ampicillin were increased and its elimination rate slowed following successive doses.
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  • 75
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    European journal of clinical pharmacology 9 (1975), S. 135-145 
    ISSN: 1432-1041
    Keywords: Anturan® ; 14C-label ; man ; pharmacokinetics ; biotransformation ; C-glucuronidation
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption, biotransformation and elimination of sulfinpyrazone, 1,2-diphenyl-3,5-dioxo-4-(2′-phenylsufinylethyl)-pyrazolidine, have been studied by administration of single 200 mg oral doses of a14C-labelled preparation to two male volunteers. Absorption from the gastro-intestinal tract was rapid and complete and the plasma concentration of unchanged drug reached maximum values of 22.67 and 13.04 µg/ml, respectively, after 1 – 2 hours. The elimination half-life in the two subjects, calculated from the decline between 3 and 8 hours, was 2.7 and 2.2 hours. The integrated concentration of unchanged sulfinpyrazone in plasma, estimated from the area under the concentration curves (AUC), was almost as high as that of total14C-substances, so the proportion of metabolized drug in plasma was low. In no case did the AUC of the three specifically determined metabolites, i.e. the sulphone G 31 442, the “para-hydroxy”-compound G 32 642 and the “4-hydroxy”-compound GP 52 097, exceed 4% of the sulfinpyrazone value. More than 95% of whole blood radioactivity was confined to plasma. The oral dose was rapidly and completely excreted, since within 4 days more than 95% was recovered, 85% from urine and 10% from faeces. A large proportion of the dose was excreted as unchanged drug in the two volunteers: 51 and 54% of total urinary radioactivity was present as sulfinpyrazone; 8.2 and 8.8% was present as “para-hydroxy”-metabolite, 2.7 and 3.0% as sulphone-metabolite, and 0.6 and 0.8% as “4-hydroxy”-metabolite. About 30% of urinary radioactivity consisted of highly polar metabolites. Spectroscopy of them showed that they were the C-β-glucuronides of sulfinpyrazone (28%) and the corresponding sulfone (2%). In these metabolites the C(4) of the pyrazolidine ring was directly attached to glucuronic acid, and thus they represent a new type of biosynthetic conjugate.
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  • 76
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    European journal of clinical pharmacology 9 (1975), S. 155-159 
    ISSN: 1432-1041
    Keywords: Anticonvulsants ; benzazepines ; clonazepam ; pharmacokinetics ; gas chromatography ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight healthy volunteers were given single i.v. and oral doses of clonazepam (2 mg). The disposition curves after i.v. administration showed a biexponential decline and the data were applied to a two-compartment open model. The volume of distribution ((Vd)β) ranged between 1.5 and 4.4 l/kg and the plasma half-life (t1/2) between 19 and 60 hours. Absorption after oral administration was fast, with peak plasma concentrations within 4 hours in all subjects. Five of the subjects received repeated oral doses of clonazepam 0.5 mg bid for 15 days. The plasma level during steady state (estimated as Cmin within the dose interval) could be predicted from the constants A, B, α and β obtained in the single dose study with a coefficient of variation of 6%. The plasma half-lives after cessation of the subchronic dosing were of the same magnitude as after single doses.
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    European journal of clinical pharmacology 9 (1975), S. 179-187 
    ISSN: 1432-1041
    Keywords: Etilefrine ; pharmacokinetics ; metabolism ; first-pass effect
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and metabolic studies with3H-etilefrine were performed to assess the importance of a first-pass effect on the pharmacodynamic action of this sympathomimetic amine. Identical amounts of3H-activity, ca. 80% of the dose, were excreted in the urine after intravenous or oral administration, which indicates complete enteral absorption of the drug. Comparison of the areas under the plasma curves of unchanged etilefrine after both routes of administration resulted in a bioavailability factor of 0.55, which can be explained by an extensive first-pass effect. The time curve of plasma levels of etilefrine was compatible with an open 2-compartment model characterized by a rather large volume of distribution (Vd, β) of 160 1, and a predominant half life of 2 hours. The pharmacodynamic action corresponded to the amount of drug in the central compartment. The major pathway of metabolism of etilefrine was conjugation to form the phenolic sulphate, and a very minor proportion of the drug was excreted as the corresponding hydroxymandelic acid. This metabolic pattern seems to confirm our hypothesis that phenylalkylamines with the hydroxyl group in the m-position of the benzene ring are predominantly conjugated in contrast to p-hydroxylated compounds which are mainly deaminated.
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  • 78
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    European journal of clinical pharmacology 9 (1975), S. 169-178 
    ISSN: 1432-1041
    Keywords: Heptabarbital ; heptabarbital sodium ; pharmacokinetics ; plasma concentration ; single and multiple dose kinetics ; relative bioavailability ; urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method has been developed for the quantitative determination of heptabarbital [5-(1-cyclohepten-1-yl)-5-ethylbarbituric acid] in human plasma after administration of single therapeutic doses of the drug. It involves a single extraction step followed by gas chromatography with alkali flame ionization detection, and the results were linear in the concentration range 0.125 – 5.0 µg/ml plasma. The pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium were studied in a crossover design in 7 healthy volunteers after oral administration of 20 tablets containing 200 mg heptabarbital and hard gelatine capsules containing an equivalent amount of its sodium salt. Heptabarbital concentrations in plasma were determined at regular intervals. The absorption of heptabarbital from the tablets was quite slow and peak level times varied from 1.5 to 4 h. The sodium salt was absorbed more rapidly and peak concentrations occurred between 1/3 and 2 h. In all cases the elimination of heptabarbital could be described by a single first-order process with an average half-life of 7.6 h (range 6.1 – 11.2 h). The half-life of the drug in each individual was about the same in the two trials. The relative bioavailability in each volunteer was estimated by comparing the areas under the plasma concentration curves. The sodium salt had an average bioavailability of 83% relative to the free acid. In some volunteers urinary excretion of unchanged heptabarbital was measured; cumulative excretion amounted to 0.16 – 0.30% of the administered dose. Four volunteers received one tablet each night for eight or ten days, but no accumulation was found. In three volunteers the half-life of the drug prior to and after these experiments did not change, whereas in the other volunteer the half-life decreased from 7.1 to 4.6 h. The possibility of enzyme induction should be considered when heptabarbital is taken regularly. It was concluded that heptabarbital was a suitable drug for the treatment of insomnia, since its half-life was rather short. Heptabarbital sodium may be used for induction of sleep, whereas Medomin® tablets, i.e. heptabarbital free acid, may be prescribed when the maintenance of sleep is the primary reason for treatment with a hypnotic drug.
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    European journal of clinical pharmacology 9 (1975), S. 199-207 
    ISSN: 1432-1041
    Keywords: Indomethacin ; acetylsalicylic acid ; drug interaction ; oral and rectal dosing ; serum levels ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A clinical-pharmacological study was performed to determine the effect of acetylsalicylic acid upon the serum concentration of indomethacin. 14 rheumatic patients were given indomethacin orally (25 mg × 4 for 4 days) and concurrently acetylsalicylic acid 3.7 g orally (0.9 g × 3 and 1.0 g × 1 daily), and 21 rheumatic patients were given indomethacin rectally in the morning (100 mg × 1) and concurrently acetylsalicylic acid 3.7 g orally (0.9 g × 3 and 1.0 g × 1 daily). On comparison with treatment with oral or rectal indomethacin alone, it was found that peak serum concentrations of indomethacin were significantly reduced (1% level), the times of the peaks were not shifted, and the areas beneath the serum concentration curves of indomethacin were smaller, but significantly so only if compared with rectal administration. In 12 rheumatic patients given indomethacin by rectum in the evening (100 mg × 1) and concurrently acetylsalicylic acid 3.7 g (0.9 g × 3 and 1.0 g × 1 daily), the serum level of indomethacin on the following morning (after 11 h) did not differ from that found after rectal treatment. A statistically but not biologically significant difference was observed between the mean serum half-lives of indomethacin given orally and rectally. For unknown reasons, concurrent doses of acetylsalicylic acid and indomethacin made the mean serum half-life of indomethacin longer than after its oral administration, but shorter than when the same dose of indomethacin was given rectally. There was no difference between serum levels of salicylate after oral administration of acetylsalicylic acid alone or after a concurrent oral or rectal dose of indomethacin. The results have been related to those reported previously, with respect to the interaction between indomethacin and acetylsalicylic acid, the serum levels of indomethacin after oral and rectal dosing, and the serum half-life of indomethacin based upon a one- or two-compartment model. The clinical relevance of the study is discussed.
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    European journal of clinical pharmacology 9 (1975), S. 229-234 
    ISSN: 1432-1041
    Keywords: Quercetin ; flavonoids ; pharmacokinetics ; absorption ; disposition ; metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quercetin, a flavonoid, have been studied in 6 volunteers after single intravenous (100 mg) and oral (4 g) doses. The data after iv administration were analyzed according to a two compartment open model with half lives of 8.8±1.2 min for the α phase and 2.4±0.2 h for the β phase (predominant half life), respectively. Protein binding was 〉98%. The apparent volume of distribution was small at 0.34±0.03 l/kg. Of the intravenous dose 7.4±1.2% was excreted in urine as a conjugated metabolite, and 0.65±0.1% was excreted unchanged. After oral administration no measurable plasma concentrations could be detected, nor was any quercetin found in urine, either unchanged or in a metabolized form. These results exclude absorption of more than 1% of unchanged drug. Recovery in faeces after the oral dose was 53±5%, which suggests extensive degradation by microorganisms in the gut. The data obtained show that oral administration of flavonoids may be of questionable value.
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    European journal of clinical pharmacology 9 (1976), S. 327-332 
    ISSN: 1432-1041
    Keywords: Antipyrine ; pharmacokinetics ; half-life ; blood ; plasma ; saliva ; individual variation
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A previously described GLC method has been modified and applied to measurement of antipyrine levels in plasma, blood and saliva of man following administration of a single oral dose (10 mg/kg). The levels in blood and saliva were comparable to those in plasma at every time studied. The half life of antipyrine determined in blood, plasma or saliva in any given individual was similar. The intersubject variation in half-life was about two-fold (n=5). Antipyrine levels in saliva were not affected by the rate of saliva flow when collections were made continuously for 20 minutes. This study has demonstrated that kinetic data about antipyrine comparable to that from plasma may also be obtained from readily accessible tissue fluids, such as saliva and capillary blood.
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  • 82
    ISSN: 1432-1041
    Keywords: Chlorthalidone ; diuretics ; drug plasma concentration ; protein binding ; red blood-cell concentration ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A gas chromatographic method has been employed to determine chlorthalidone in plasma and whole blood after therapeutic doses. Radioactively labelled chlorthalidone was used for in vitro studies of the uptake of chlorthalidone from plasma by red blood cells. Chlorthalidone was markedly concentrated in red cells and as a compartment they would account for at least 30% of total drug in the body after multiple doses. The ratio between the plasma and red cell concentration of chlorthalidone varied between individuals. After a single oral dose of 50 mg in 6 healthy volunteers chlorthalidone was eliminated with a half-life of 51 to 89 hours. The apparent volume of distribution varied between 3 and 13 1/kg and the clearance between 53 and 145 ml/min. The mean steady-state plasma concentrations during treatment with a standard dose of 50 mg daily (n=10) varied 5-fold between individuals. During the steady state approximately 50% of the daily dose was excreted unchanged in the urine during 24 hrs. The plasma levels observed in patients were higher than those predicted from the single oral dose studies in healthy volunteers.
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  • 83
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    European journal of clinical pharmacology 9 (1976), S. 367-372 
    ISSN: 1432-1041
    Keywords: Sotalol ; β-adrenoceptor blocking drugs ; exercise tachycardia ; efficacy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of sotalol after oral administration were measured on the tachycardia induced by strenuous exercise in normal subjects. Plasma sotalol levels were also determined. The oral administration of sotalol (50, 100, 200 and 400 mg) to 6 subjects produced a progressive reduction in the tachycardia induced by severe exercise. This was similar to the effects of 25, 50, 100, 200, 400 and 800 mg given to different subjects. Each increase in sotalol dose produced a successively greater reduction in exercise tachycardia. This did not appear to be maximum even with 800 mg. Oral sotalol was rapidly absorbed and produced peak blood levels in 2 – 3 hours. The plasma levels of sotalol measured 2 hours after the oral administration of 25 to 800 mg showed never more than a six-fold variation between different subjects. The half-life of sotalol in plasma was 12.7 ± SE 1.6 hours. There was a significant correlation between the logarithm of the plasma sotalol concentration and the percentage reduction of exercise heart rate. It is concluded that the oral administration of sotalol either once or twice daily (depending on dose level) will provide satisfactory 24-hour blockade of β-adrenoceptors.
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    European journal of clinical pharmacology 9 (1976), S. 443-450 
    ISSN: 1432-1041
    Keywords: Cyclobarbital calcium ; pharmacokinetics ; plasma concentration ; relative bioavailability ; oral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and relative bioavailability of cyclobarbital calcium have been studied after oral administration of Phanodorm, of tablets according to the Formularium Nederlandse Apothekers (1968; FNA), and an aqueous solution. Six healthy volunteers participated in the investigation on three occasions and each received the three preparations. The dose administered was 300 mg cyclobarbital calcium. Plasma concentrations of cyclobarbital were determined at regular intervals. Absorption from the three preparations was rapid and was faster from the solution. Peak concentrations were usually attained within 1 h. The elimination of cyclobarbital could be described by a single first-order process with an average half-life of 11.6 h (range 8 – 17 h). There was little intra-subject variation of the half-life. Relative bioavailability for each volunteer was estimated by comparing the areas under the plasma concentration curves. The FNA-tablets and Phanodorm exhibited similar bioavailability, whereas the average bioavailability of the solution was 78% of that of FNA-tablets; the reason for this unexpected finding is unknown. It was concluded that cyclobarbital cannot be regarded as a uniformly suitable drug for the treatment of insomnia. The long half-life that was apparent in some of the volunteers (15 – 17 h) creates a substantial risk of residual effects on the following morning. In principle, however, the calcium salt of cyclobarbital may be used for induction of sleep, because of its rapid absorption.
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    European journal of clinical pharmacology 8 (1975), S. 63-69 
    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; sulfonylurea ; glipizide ; glibenclamide ; pharmacokinetics ; excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Four subjects received 5 mg14C-glipizide orally, 3 subjects 1 mg intravenously and 2 subjects 5 mg14C-glibenclamide orally. Plasma levels of radioactivity, and urinary and faecal excretion were measured. For both drugs the disappearance of radioactivity from plasma followed complex kinetics and the apparent half-lives increased steadily with time. The two sulfonylureas were extensively metabolized and were excreted in the urine as hydroxylated or conjugated metabolites. The effects of both drugs on blood glucose and immunoreactive insulin were comparable. The findings are compared with other published results.
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    European journal of clinical pharmacology 8 (1975), S. 91-96 
    ISSN: 1432-1041
    Keywords: Carbamazepine ; pharmacokinetics ; man ; diphenylhydantoin ; phenobarbital ; plasma binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carbamazepine (2.7–3 mg/kg) was administered orally as an alcoholic solution (50% v/v) to eight healthy volunteers. Two of the subjects were also given 50 mg and 100 mg of carbamazepine in alcoholic solution and 200 mg as a tablet. Plasma concentrations, which were analysed by mass fragmentography, reached a maximum 1 – 7 hours after dosing, and then declined monoexponentially with half-lives ranging from 24 to 46 hours. The half-lives were independent of dose. The apparent distribution volume ranged from 0.79 to 1.40 l/kg. It was found that 72% of carbamazepine was bound to plasma proteins with little interindividual variation, and this was not influenced by the presence of diphenylhydantoin or phenobarbital in therapeutic concentrations. The pharmacokinetic parameters calculated from single oral doses were used to predict the steady-state plasma concentration expected after treatment with multiple doses of 200 mg three times daily. The predicted steady-state concentration was 2 – 3 times higher than that reported in patients undergoing chronic treatment with carbamazepine at this dose level, i.e. the pharmacokinetics of carbamazepine apparently change during multiple dosing.
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    European journal of clinical pharmacology 8 (1975), S. 217-222 
    ISSN: 1432-1041
    Keywords: Co-trimoxazole ; sulphamethoxazole ; trimethoprim ; pharmacokinetics ; paediatric-prescribing ; dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Co-trimoxazole, a mixture of one part trimethoprim (TMP) and five parts of sulphamethoxazole (SMX) in fixed ratio was given to 48 children aged between one and 48 months twice daily for up to seven days. Twenty were relatively healthy and 28 were very ill. Dosage was based on age. Plasma concentrations of both drugs were measured just before a dose was due and some three hours later. They were in the effective but not toxic range and serve to justify the simple regimen which generated them.
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    European journal of clinical pharmacology 8 (1975), S. 255-260 
    ISSN: 1432-1041
    Keywords: Vitamin D ; renal osteodystrophy ; 5,6-trans-25-hydroxycholecalciferol ; rickets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Vitamin D analogues of high biological activity are probably useful in the treatment of renal osteodystrophy. The pharmacokinetics of the synthetic compound 5,6-trans-25-hydroxycholecalciferol have been studied in healthy subjects who were of normal vitamin D status. In comparison to natural 25-hydroxy-cholecalciferol, serum levels of the analogue were lower and its half-life in blood after oral or intravenous administration was considerably shorter. In normal subjects no increase of dihydroxylated metabolites in serum was observed within seven days of an intravenous dose.
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    European journal of clinical pharmacology 8 (1975), S. 353-357 
    ISSN: 1432-1041
    Keywords: Chlormethiazole ; pharmacokinetics ; man ; plasma levels ; gas-liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole have been studied in six healthy volunteers following an intravenous infusion of the drug. The log. plasma concentration-time curve of chlormethiazole after cessation of the infusion was found to be curvilinear and was fitted therefore, by a bi-exponential equation computed by non-linear least squares regression analysis. Half-lives for the inital α-phase (0.54±0.05 h) and the terminal β-phase (4.05 ±0.60 h) were calculated together with other pharmacokinetic parameters of the two compartment open model. An explanation for the discrepancy between the presently reported plasma half-lives and those appearing in the literature has been presented. The pharmacokinetic treatment of the plasma concentration-time data obtained following intravenous infusion also enabled the prediction that the maximal systemic availability of an orally administered dose of chlormethiazole would be of the order of 15%.
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  • 90
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    European journal of clinical pharmacology 16 (1979), S. 203-209 
    ISSN: 1432-1041
    Keywords: dantrolene sodium ; spasticity ; twitch tension ; dose response ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dantrolen sodium is a muscle relaxant, which is used in the treatment of spasticity. Although it is given chronically, little is known about its pharmacokinetic behaviour. The relationship between the effect of a single oral dose of dantrolene sodium and its plasma concentration in healthy volunteers was studied by measuring the effect on the twitch tension, and in spastic patients on the decrease in muscle hypertonia. On the twitch tension dantrolene gave a depression of 49.1±9.4% (±SD) within 1.15 and 3.45 h after ingestion of 100 mg. The mean maximal plasma concentration was 1.24±0.32 µg/ml (±SD). The effect and the plasma concentration were correlated. No relationship between the plasma concentration of dantrolene sodium and its effect could be established in patients, although definite activity in 6 out of 7 patients was observed after a single oral dose of 100 mg, and plasma concentration of dantrolene sodium greater than 0.3 µg/ml were consistently associated with better results than placebo treatment in 6 out of 7 patients.
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  • 91
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    European journal of clinical pharmacology 16 (1979), S. 287-293 
    ISSN: 1432-1041
    Keywords: linear system theory ; perfusion model ; cardiac output ; pulmonary extraction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Assessment of pharmacokinetics in terms of circulatory drug transport is proposed using the methods of linear system theory. In this model-independent approach drug distribution and disposition are characterized by the total extraction ratio, the mean residence time in the body and the volume of distribution at steady state. In analyzing concentration(c)-time(t) data, the procedure requires calculation only of the areas under the c(t)-and c(t)×t-curves to estimate kinetic parameters, and for prediction of the steady state concentration following continuous infusion or multiple doses. Pulmonary clearance of drugs is included in the theory.
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  • 92
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    European journal of clinical pharmacology 10 (1976), S. 251-256 
    ISSN: 1432-1041
    Keywords: Sisomicin ; pharmacokinetics ; bioavailability ; two-compartment analysis ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sisomicin, a new single component aminoglycoside antibiotic related to gentamicin c1a, were determined in four healthy volunteers after intravenous and intramuscular administration of a 1 mg/kg dose. The elimination profile of this antibiotic follows two-compartment model kinetics after I.V. administration. The fast (α) and slow (β) disposition rate constants averaged 0.072 and 0.004 min−1, respectively. The volume of distribution at the steady-state averaged 0.185 liters/kg which approximately corresponds to the volume of extracellular space. The physiological availability of an intramuscular dose appeared to be complete. A method of administration adapted to the kinetic properties of the drug is proposed.
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  • 93
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    European journal of clinical pharmacology 10 (1976), S. 311-317 
    ISSN: 1432-1041
    Keywords: Hydralazine ; instability of impaired renal function ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following a single 50 mg dose of hydralazine (Apresoline®) in 13 patients with impaired renal function, a decrease in glomerular filtration rate (GFR) was correlated with an increase in serum half-life (T1/2) of the drug (r=−0.69; p〈0.01). The T1/2 was 15.8 h in one patient with a GFR of 16 ml·min−1, as compared to a T1/2 of 1.7–3.0 h found previously in 16 healthy volunteers. In 49 patients on long-term antihypertensive treatment with hydralazine, the ratio between the minimum steady-state drug concentration and the daily dose of hydralazine (C SS min : Dose) increased as the GFR decreased. This accumulation of the drug was particularly evident in patients with a GFR less than 30 ml·min−1 (r=−0.63; p〈0.01; n=19). As renal excretion of unchanged hydralazine is generally regarded as unimportant, the slower elimination rate in chronic renal failure was probably caused by a slower rate of metabolic conversion. It was found, however, that the renal excretion of hydralazine could easily have been underestimated, as only 12.7% of an initial hydralazine concentration of 200 ng·ml−1 in urine could be recovered after storage of the samples at room temperature for 24 h.
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  • 94
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    European journal of clinical pharmacology 10 (1976), S. 325-330 
    ISSN: 1432-1041
    Keywords: Flutiorex ; pharmacokinetics ; sex ; anorectic agent ; sympathetic stimulation ; CNS stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of flutiorex, a new anorectic agent, and of a placebo on food intake and the activity of the sympathetic and central nervous systems have been compared in a double blind trial in two groups of healthy volunteers, one of five males and the other of five females. Flutiorex 20 mg orally had a significant anorectic effect both in males and females, the observed reduction in food intake being 34.0 and 27.5%, respectively. It caused α-adrenergic stimulation (blood pressure and pupil diameter) and central nervous system excitation (critical flicker frequency), both of which were more marked in males than in females. Flutiorex was better tolerated by women than by men. Measurement of the blood level of flutiorex and its de-ethylated metabolite, norflutiorex, showed that both compounds were detectable in four of the five male subjects, but in only one of the five females. Sex-linked differences in the pharmacokinetics of flutiorex may explain the greater intensity of its effects in males.
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  • 95
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    European journal of clinical pharmacology 10 (1976), S. 343-347 
    ISSN: 1432-1041
    Keywords: Methaqualone ; hypnotic ; pharmacokinetics ; combination formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Concentrations of methaqualone have been measured in the serum of five male human subjects receiving five consecutive evening doses of a combination formulation containing methaqualone (250 mg), carbromal (300 mg) and benactyzine (0.33 mg) in each tablet. After administration of the first dose, mean peak serum concentrations of methaqualone (1.2 µg/ml) occurred at 3 h. After obtaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h and there-after more slowly during the next 18 h. After administration of the last (fifth) dose, mean peak serum concentrations of methaqualone (1.9 µg/ml; 1.5 µg/ml above the predose level) occurred at 2 h. After attaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h, and thereafter more slowly, with a half-life of approximately 10 h. Mean concentrations of methaqualone in serum samples 24 h after the second, third, fourth or fifth doses were not significantly different (0.3 µg/ml – 0.6 µg/ml) during this period of dosing. This suggests that significant accumulation of methaqualone in the serum did not occur during a period of five consecutive evening doses of the combination formulation.
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  • 96
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    European journal of clinical pharmacology 12 (1977), S. 137-145 
    ISSN: 1432-1041
    Keywords: Chlormethiazole ; pharmacokinetics ; metabolites ; oral administration ; young and elderly human subjects ; quantitative gas chromatographymass spectrometry ; whole blood distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration of chlormethiazole and two of its metabolites has been measured in three young and three aged human subjects following administration of a single oral dose of chlormethiazole. A sensitive analytical method based on gas chromatography-mass spectrometry using the selective ion monitoring mode of operation was developed to permit quantitation of the plasma levels. The time course of the plasma concentration of chlormethiazole and metabolites showed wide inter-subject variation, particularly between the young and elderly subjects. Absorption of chlormethiazole was rapid in the subjects of both groups as assessed by the time taken to reach the peak plasma concentration. The mean peak plasma level of chlormethiazole was more than five times greater in the elderly (2.90±1.56 µg/ml) than in the young (0.55±0.58 µg/ml) subjects. The plasma level of chlormethiazole was consistently higher in the aged subjects and this was reflected by the larger area under the plasma curve in aged (7.62±5.37 µg.h/ml) than in young (0.94±0.66 µg.h/ml) individuals. Decreased pre-systemic elimination by the liver has been suggested as an important factor contributing to the higher plasma level in the elderly. Estimates of absolute systemic availability, calculated by reference to previous intravenous studies, were greater for the elderly subjects. The distribution of chlormethiazole in whole blood from six young and six elderly human subjects was investigated in vitro. The unbound fraction of chlormethiazole in plasma increased significantly from 0.308±0.035 in young subjects to 0.403±0.067 in the elderly. Distribution of the drug in whole blood was different for the two age groups; the fraction of drug distributed to plasma water was significantly greater and the fraction in blood cells was significantly less in the aged.
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  • 97
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    European journal of clinical pharmacology 12 (1977), S. 171-174 
    ISSN: 1432-1041
    Keywords: Tolamolol ; hypertension ; pharmacokinetics ; mean steady-state concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolamolol was administered in a “double-blind” study to fifteen hypertensive patients by dose-titration against arterial blood pressure. Mean steady-state plasma tolamolol concentrations (Css) were determined for each patient from the area under the plasma concentration — time curve during a dosage interval whilst patients were receiving optimal tolamolol doses. No significant correlation was observed between daily tolamolol dose and Css; the relationship between fall in lying mean arterial pressure and Css also failed to reach conventional levels of statistical significance, but Css was observed to be correlated with the fall in standing pressure. The results suggest that plasma concentrations in excess of 200 ng/ml may be required to achieve an effective hypotensive response with the drug.
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  • 98
    ISSN: 1432-1041
    Keywords: Muzolimine ; pharmacodynamics ; pharmacokinetics ; furosemide ; saluresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a biometrically planned, double-blind study on 12 Oedema-free male patients the saluretic effect of muzolimine 30 mg was compared with furosemide 40 mg. The plasma level of muzolimine was determined and correlated with its pharmacodynamics. In terms of excretion during the 12-hour observation period muzolimine 30 mg had as great a cumulative effect as furosemide 40 mg. There was a significant difference in the time-response curve. During the first two hours furosemide 40 mg had more saluretic effect than muzolimine 30 mg. Between two and four hours there was no significant difference between the two substances. Between four and six hours, however, muzolimine was somewhat more effective than furosemide, although the difference did not reach the level of significance. After 6 h there was no longer any difference between the two compounds. The half-life of the fall in concentration of muzolimine in plasma was 3.7 up to 10 h after its administration. The time-response curve of the increased urine excretion correlated well with the time course of the concentration of muzolimine in plasma.
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  • 99
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    European journal of clinical pharmacology 12 (1977), S. 125-132 
    ISSN: 1432-1041
    Keywords: Valproic acid ; pharmacokinetics ; saliva concentration ; urinary excretion ; serum protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of valproic acid (VPA) have been studied in 6 healthy subjects following a single 600 mg dose, and after multiple doses over 12 days (1200 mg daily) of enteric-coated sodium valproate. A time lag before absorption of 1 to 2 h was observed in each subject, and then absorption was rapid, peak concentrations being recorded 3 to 4 h after administration of the dose. The plasma level decline was biphasic with a terminal half-life of 15.9±2.6 h in the single dose and 17.3±3.0 h in the multiple dose experiments. There was no evidence of dose dependent kinetics or autoinduction. Total plasma clearance was 0.0064±0.0011 l/kg×h. The apparent volume of distribution was small at 0.15±0.2 l/kg. The mean steady state plasma concentration (Css) reached after 4 days was 81.3±13.0 µg/ml. Css observed was lower than Css predicted (99.2±14.7 µg/ml) from single dose kinetics (p〈0.001). The difference was probably due to a reduction in plasma protein binding at higher concentrations. VPA concentration in saliva was between 0.4 and 4.5% of the total plasma concentration and was not equal to the concentration of unbound drug in plasma (6.7±0.8% unbound). 3.2% of the dose was excreted in urine as the parent drug and 21.2% as conjugated metabolites.
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  • 100
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    European journal of clinical pharmacology 12 (1977), S. 367-373 
    ISSN: 1432-1041
    Keywords: Sulphamethizole ; tetracycline ; doxycycline ; rest ; exercise ; pharmacokinetics ; excretion ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The serum level and urinary excretion of sulphamethizole, tetracycline and doxycycline were studied in healthy volunteers subjected to intensive exercise and bed rest in a cross-over trial. Each group consisted of 7–8 subjects. The exercise or bed rest began 15 min before oral administration of the drug and was continued for the following 4 hours. During exercise serum drug concentration and the area under the serum concentration-time curve for each agent was significantly higher (p〈0.05) than the corresponding values at rest. Exercise greatly suppressed the renal excretion of tetracycline and doxycycline, but the decrease alone appeared insufficient to account for the pronounced increase in serum drug concentration. Total drug excretion in urine was unchanged. Thus, it seemed most unlikely that overall absorption from the gastrointestinal tract had been altered by exercise. However, the rate of absorption appeared to be more rapid in the exercise than in the rest period. Marked haemoconcentration was not produced by the exercise. In addition to changes in absorption and elimination rates, alteration in the volume of distribution might contribute to the higher serum drug concentration during exercise. Therefore, the level of physical activity should be considered in the interpretation of pharmacokinetic data both in clinical practice and in pharmacokinetic studies.
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