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  • pharmacokinetics  (41)
  • Phytochrome  (22)
  • Springer  (63)
  • Krefeld : Geologischer Dienst Nordhein-Westfalen
  • Wien : Geolog. Bundesanst.
  • 2010-2014
  • 2005-2009
  • 1975-1979  (63)
  • 1940-1944
  • 1978  (63)
Collection
Keywords
Publisher
  • Springer  (63)
  • Krefeld : Geologischer Dienst Nordhein-Westfalen
  • Wien : Geolog. Bundesanst.
Years
  • 2010-2014
  • 2005-2009
  • 1975-1979  (63)
  • 1940-1944
Year
  • 1
    Electronic Resource
    Electronic Resource
    Evidence of phytochrome involvement in the entrainment of the circadian rhythm of carbon dioxide metabolism in Bryophyllum (1978)
    Springer
    Planta 138 (1978), S. 271-278 
    Details
    ISSN: 1432-2048
    Keywords: Bryophyllum ; Circadian rhythm ; CO2 output ; Phytochrome ; Red light ; Rhythm (circadian)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The rhythm of carbon dioxide output in Bryophyllum leaves was entrained on exposure to 0.25 h of white light every 24 h. Entrainment also occurred on similar exposure to monochromatic radiation in spectral bands centred at 660 nm and, to a lesser extent, at 730 nm, but a band centred at 450 nm was without effect. A “skeleton” irradiation programme comprising two 0.25-h exposures to white light per 24 h also entrained the rhythm when the intervening dark periods were either 7.5 h and 16 h, or 10.5 h and 13 h. The rhythm disappeared when the two exposures were separated by 11.5-h and 12-h dark periods. Regular 0.25-h exposures to red light separated by 11.75-h periods of darkness also resulted in loss of the rhythm. Red/far-red reversibility was observed in irradiation schedules having either one or two exposures to red light daily. In the latter case, far-red reversal of the effects of one of the exposures to red light resulted in entrainment of the rhythm by the other, instead of abolition of the rhythm. The occurrence of distinct red/far-red reversibility suggests strongly that phytochrome is the pigment involved in entrainment of this rhythm by cycles of light and darkness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00386822
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  • 2
    Electronic Resource
    Electronic Resource
    Distorted phytochrome action spectra in green plants (1978)
    Springer
    Planta 138 (1978), S. 25-28 
    Details
    ISSN: 1432-2048
    Keywords: Action spectrum ; Chlorophyll ; Phaseolus ; Photomorphogenesis ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Red light absorption by photosynthetic pigments screens stem tissue of Phaseolus vulgaris L. seedlings to such an extent that the most effective wavelength for the phytochrome induction control of stem growth is approximately 628 nm. Screening is greater in the first internode than in the hypocotyl. The consequences are that, compared with etiolated seedlings, much higher irradiances are required for phytochrome control in green plants, and the efficiency of 660 nm light is markedly reduced. Even very high exposures at 660 nm may not achieve appreciable photoconversion of P r to P fr.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00392909
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of narrow-beam irradiations with blue and far-red light on the timing of cell division in Adiantum gametophytes (1978)
    Springer
    Planta 138 (1978), S. 85-90 
    Details
    ISSN: 1432-2048
    Keywords: Adiantum ; Blue-light effect ; Cell division ; Light, microbeam ; Photomorphogenesis ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Protonemata of the fern Adiantum capillusveneris L., grown as single-cell filaments under continuous red light, were irradiated with a narrow beam of blue light. Only irradiation of the region containing the nucleus induced cell division. Beams of 30 μm in width, which corresponds to the diameter of the nucleus, or wider, were equally effective; beams 10 μm wide or less were less effective. The results indicate that the nuclear region is the site of the blue- and near ultraviolet-light-absorbing pigment (PB-NUV) which mediates the timing effect of cell division. In contrast, the effect of a narrow beam of far-red (FR) light, which delays the onset of the blue-light-induced cell division, was found to be present along the entire length of the protonema cell, including the largely vacuolated basal region of the latter. Polarized FR light having the electrical vector parallel to the protonema axis was less effective than that vibrating in other directions. These observations support the hypothesis that the phytochrome controlling the timing effect is localized in the plasma membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00392921
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  • 4
    Electronic Resource
    Electronic Resource
    Phytochrome-mediated changes in the membrane potential of subepidermal cells of Lemna paucicostata 6746 (1978)
    Springer
    Planta 138 (1978), S. 133-136 
    Details
    ISSN: 1432-2048
    Keywords: Lemna ; Membrane potential ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Light-stimulated transmembrane potential changes have been measured continuously after implantation of microelectrodes into subepidermal cells of the short-day plant Lemna paucicostata 6746. Irradiation for 5 min with white or red light caused a transient hyperpolarization. These potential changes could be suppressed with 10-6 M DCMU. Irradiation of DCMU-inhibited plants with far-red light for 5 min hyperpolarized the membrane potential, which thereafter was not changed by further far-red application. Consecutive red light irradiation for 5 min depolarized the membrane potential. The red/far-red reversibility of the potential changes (which could be repeated several times with a single plant) suggests the participation of phytochrome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00391169
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  • 5
    Electronic Resource
    Electronic Resource
    Light requirement, phytochrome and photoperiodic induction of flowering of Pharbitis nil Chois (1978)
    Springer
    Planta 141 (1978), S. 1-7 
    Details
    ISSN: 1432-2048
    Keywords: Flowering ; Pharbitis ; Photomorphogenesis ; Photoperiodic induction ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract For dark-grown seedlings of Pharbitis nil capacity to flower in response to a single inductive dark period was established by 24 h white, far-red (FR) or ruby-red (BCJ) light and by a skeleton photoperiod of 10 min red (R)-24 h dark-10 min R. FR alone was ineffective without a brief terminal (R) irradiation, confirming that the form of phytochrome immediately prior to darkness is a crucial factor for flowering in Pharbitis. The magnitude of the flowering response was significantly greater after 24 h FR or white light (WL) (at 18° C and 27° C) than after two brief skeleton R irradiations, but the increased flowering response was not attributable to photosynthetic CO2 uptake because this could not be detected in seedlings exposed to 24 h WL at 18° C. Photophosphorylation could have contributed to the increased flowering response as photosystem I fluorescence was detectable in plants exposed to FR, BCJ, or WL, but there were large differences between flowering response and photosystem I capacity as indicated by fluorescence. We conclude that phytochrome plays a major role in photoresponses regulating flowering. There was no simple correlation between developmental changes, such as cotyledon expansion and chlorophyll formation during the 24-h irradiation period, and the capacity to flower in response to a following inductive dark period. Changes in plastid ultrastructure were considerable in light from fluorescent lamps and there was complete breakdown of the prolamellar body with or without lamellar stacking at 27 or 18° C, respectively, but plastid reorganization was minimal in FR-irradiated seedlings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00387736
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  • 6
    Electronic Resource
    Electronic Resource
    An in vitro association of soluble phytochrome with a partially purified organelle fraction from barley leaves (1978)
    Springer
    Planta 141 (1978), S. 71-76 
    Details
    ISSN: 1432-2048
    Keywords: Hordeum ; Membranes ; Organelles ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Red light treatment in vitro increases the pelletability of phytochrome in homogenates of etiolated barley (Hordeum vulgare L. cv. ‘Julia’) leaves. When mixtures of soluble phytochrome (100,000 x g supernatant) and partially-purified organelles (Sephadex G-50 eluate) are irradiated the amount of pelletable phytochrome increases by a factor of two. Pre-irradiation treatments show that phytochrome in both components of the mixture must be in the Pfr form for increased pelletability to be observed. Once associated, photoreversion of Pfr to Pr does not result in decreased pelletability. The results are consistent with a non-artifactual in vitro association of soluble phytochrome to organelle membranes. One possible explanation is that Pfr molecules associate to form dimers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00387747
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  • 7
    Electronic Resource
    Electronic Resource
    Phytochrome photoreversibility: Empirical test of the hypothesis that it varies as a consequence of pigment compartmentation (1978)
    Springer
    Planta 141 (1978), S. 129-134 
    Details
    ISSN: 1432-2048
    Keywords: Avena ; Immunocytochemistry ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phytochrome of oat (Avena sativa L., cv. Garry) coleoptile cells in the red-light-absorbing form, Pr, is diffusely distributed while after conversion to the far-red-light-absorbing form, Pfr, it is observed only in very small areas within the cell. Comparison of phytochrome photoversibility measurements to the distribution of the pigment within the cell indicates that the spectral assay is not influenced by the observed compartmentalization of the chromoprotein. However, the observed compartmentalization of phytochrome is correlated with a loss in spectrophotometrically detectable Pr.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00387878
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  • 8
    Electronic Resource
    Electronic Resource
    Control by light of hypocotyl growth in de-etiolated mustard seedlings (1978)
    Springer
    Planta 141 (1978), S. 211-216 
    Details
    ISSN: 1432-2048
    Keywords: Hypocotyl growth ; Photomorphogenesis ; Phytochrome ; Sinapis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract After sowing, mustard (Sinapis alba L.) seedlings were grown for 48 h in white light (25°C). These fully de-etiolated, green seedlings were used as experimental material between 48 and 72 (84) h after sowing. The question researched was to what extent control by light of hypocotyl elongation is due to phytochrome in these seedlings. It was found that the light effect on hypocotyl growth is very probably exerted through phytochrome only. In particular, we found no indication for the involvement of a specific blue light photoreceptor pigment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00387891
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  • 9
    Electronic Resource
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    Destruction and possible de novo synthesis of phytochrome in subcellular fractions of laminae from Avena sativa L. (1978)
    Springer
    Planta 141 (1978), S. 273-277 
    Details
    ISSN: 1432-2048
    Keywords: Avena ; Etioplasts ; Mitochondria ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phytochrome was determined in etiolated laminae of Avena sativaL. either without pretreatment or after 5 min of red irradiation followed by different periods of darkness (0–24 h). At given intervals laminae were homogenized and phytochrome was determined spectrophotometrically in the total homogenate and in purified etioplasts and mitochondria. Enhanced specific activity of phytochrome was found in all fractions after the irradiation in comparison to dark controls. Phytochrome destruction was observed in all fractions at the beginning of the subsequent dark period. Whereas the homogenate and the mitochondrial fraction showed a continuous destruction so that phytochrome reached a level far below that in etiolated plants, the phytochrome level in the plastid fraction reacheda minimum at 2 h with a subsequent increase beyond the dark level. This increase was most pronounced between 4 and 8 h after the red irradiation. The results are discussed in terms of the destruction and possible de novo synthesis of phytochrome that may be different in mitochondria and plastids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00388343
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  • 10
    Electronic Resource
    Electronic Resource
    Light effects upon dry lettuce seeds (1978)
    Springer
    Planta 144 (1978), S. 1-5 
    Details
    ISSN: 1432-2048
    Keywords: Germination (seeds) ; Lactuca ; Phytochrome ; Seed germination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Germination of certain dry “seeds” (achenes) of Lactuca sativa L. cv. Grand Rapids was increased to ca. 75% after irradiation with 665 nm red light (R; 1x103 J m-2); this response was eliminated by far-red light (FR) following the R. The response of dry seeds required an order of magnitude more light than that of wetted seeds, and was not maximal until 48 h after irradiation. Other seeds, which could not be stimulated by R in dry state, showed a partial response after 10 min hydration. Irradiation of dry seeds (or seeds wetted 1 h) with FR (1x103 J m-2) reduced dark germination from 26% to 2%. Seeds dehydrated in an oven (60°C, 90 min) showed a decrease in germination if irradiated with R (1x105 J m-2) before wetting. The results show that phytochrome is present in dry lettuce seeds (and functional in some seed lots) prior to wetting; and that in other seed lots the molecule becomes functional within minutes after wetting the seeds. Transformation of the FR absorbing from of phytochrome (PFR) to the inactive from (PR) occurs at lower seed moisture content than the reverse reaction. It appears that dormancy in seeds ripened in sunlight might be assured during seed drying and maturation by the more effective transformation of PFR to PR than vice versa as phytochrome is dehydrated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00385000
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  • 11
    Electronic Resource
    Electronic Resource
    Spectrophotometric phytochrome measurements in light-grown Avena sativa L. (1978)
    Springer
    Planta 143 (1978), S. 309-313 
    Details
    ISSN: 1432-2048
    Keywords: Avena ; Light-grown tissue ; Phytochrome ; San 9789
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phytochrome was studied spectrophotometrically in Avena sativa L. seedlings that had been grown for 6 d in continous white fluorescent light from lamps. Greening was prevented through the use of the herbicide San 9789. When placed in the light, phytochrome (Ptot) decreased with first order kinetics (τ1/2 ≈ 2 h) but reached a stable low level (≈2.5% of the dark level) after 36 h. This concentration of phytochrome remained constant in the light and during the initial hours of a subsequent dark period, but increased significantly after a prolonged dark period. Evidence suggests that the constant pool of phytochrome in the light is achieved through an equilibrium between synthesis of the red absorbing (Pr) and destruction of the far-red absorbing form (Pfr) of phytochrome. It is concluded that the phytochrome system in light-grown oat seedlings is qualitatively the same as that known from etiolated monocotyledonous seedlings, but different than that described for cauliflower florets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00392003
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  • 12
    Electronic Resource
    Electronic Resource
    The circadian rhythm in Bryophyllum leaves: Phase control by radiant energy (1978)
    Springer
    Planta 143 (1978), S. 323-328 
    Details
    ISSN: 1432-2048
    Keywords: Bryophyllum ; Circadian rhythm ; Photocontrol ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A 4-h exposure to white light from fluorescent lamps can shift the phase of the rhythm of CO2 output in leaves of Bryophyllum fedtschenkoi Hamet & Perr. otherwise kept in continuous darkness. The position in the cycle at which irradiation occurs determines the magnitude and direction of the phase shift. Red and white light induce similar advances or delays in the phase, but blue and far-red irradiation have no effect. Far-red irradiation given simultaneously with, or immediately after, exposure to red light, modifies the phase-shift induced by red light alone. Radiation in the red and far-red regions of the spectrum interacted in several experimental régimes, but complete red/far-red reversibility was not observed. The evidence suggests that phytochrome is the receptor molecule involved in the induction of phase-shifts by light.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00392005
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  • 13
    Electronic Resource
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    Action spectra for chromatic adaptation in the blue-green alga Fremyella diplosiphon (1978)
    Springer
    Planta 143 (1978), S. 233-239 
    Details
    ISSN: 1432-2048
    Keywords: Adaptation (chromatic) ; Chromatic adaptation ; Cyanophyta (cyanobacteria) ; Phycobiliproteins ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Action spectra for chromatic adaptation in Fremyella diplosiphon Drouet have been determined using techniques previously described. Action maxima are at 540 nm, with a half-band width of 80 nm, for induction of phycoerythrin synthesis (green action) and at 650 nm, with a half-band width of 90 nm, for reversal of induction of phycoerythrin synthesis (red action). The red-action spectrum includes a secondary action band centered at ca. 360 nm. Red and green action overlap from 570 to 590 nm with an isosbestic point in the vicinity of 580 nm. Shoulders are present at 520 and 630 nm. Red light is more active than green light. The 540:650-nm quantum effectiveness ratio is 1:7. There is relatively little action of either kind in the blue. The 387:540 nm and 460:650-nm quantum effectiveness ratios are zero. These results contrast strongly with previous determinations in the same organism, with major activity indicated in the blue; they are consistent with the control of photomorphogenesis in the Cyanophyta by a master pigment, analogous to phytochrome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00391993
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  • 14
    Electronic Resource
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    Light requirement, phytochrome and photoperiodic induction of flowering of Pharbits nil Chois (1978)
    Springer
    Planta 141 (1978), S. 9-14 
    Details
    ISSN: 1432-2048
    Keywords: Flowering ; Pharbitis ; Photoperiodic induction ; Phytochrome ; Spectrophotometry (phytochrome)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The low chlorophyll content of cotyledons of Pharbitis nil grown for 24 h in far-red light (FR) or at 18° C in white light from fluorescent lamps (WL) allows spectrophotometric measurement of phytochrome in these tissues. The Δ(ΔA) measurements utilize measuring beams at 730/802 nm and an actinic irradiation in excess of 90 s. The constancy of the relationship between phytochrome content and sample thickness confirms that, under these conditions of measurement, a true maximum phytochrome signal was obtained. These techniques have been used to follow changes in the form and amount of phytochrome during an inductive dark period for flowering. Following exposure to 24h WL at 18° C with a terminal 10 min red (R), Pfr was lost rapidly in darkness and approached zero in less than 1 h; during this period there was no change in the total phytochrome signal. Following exposure to 24 h FR with a terminal 10 min R, Pfr approached zero in 3 h, and the total phytochrome signal decreased by about half. The relevance of these changes to photoperiodic time measurement is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00387737
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  • 15
    Electronic Resource
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    Light requirement, phytochrome and photoperiodic induction of flowering of Pharbitis nil Chois (1978)
    Springer
    Planta 141 (1978), S. 15-22 
    Details
    ISSN: 1432-2048
    Keywords: Flowering ; Pharbitis ; Photoperiodic induction ; Phytochrome ; Spectrophotometry (phytochrome)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract During an inductive dark period for flowering, changes in phytochrome have been followed in cotyledons of Pharbitis nil seedlings using a spectrophotometric and a physiological technique. There was agreement between the two techniques, both indicating a rapid lowering of the levels of the far-red-absorbing form of the pigment (Pfr) during the first 30–90 min of darkness. Thus, Pfr could provide the cue which signals the beginning of darkness and the length of the critical dark period was, in some instances, correlated with the time of Pfr disappearance. However, there was no correlation with another indicator of photoperiodic time measurement, the time in darkness at which a brief night interruption becomes inhibitory to flowering. These results imply that the transition from light to darkness is not signalled by the disappearance of Pfr. However, the involvement of other photoreceptors seems unlikely. Thus, some mode of phytochrome action other than a simple Pfr-mediated response may be involved in the light/dark-sensing reactions of photoperiodism
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00387738
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  • 16
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    Phytochrome-mediated control of grana and stroma thylakoid formation in plastids of mustard cotyledons (1978)
    Springer
    Planta 141 (1978), S. 191-198 
    Details
    ISSN: 1432-2048
    Keywords: Chlorophyll ; Chloroplasts ; Grana ; Phytochrome ; Sinapis ; Thylakoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The etioplast»chloroplast transition in the cotyledons of mustard seedlings (Sinapis alba L.) has been studied by electron microscopy. It was found that the active form of phytochrome, established by a red light pulse pretreatment, increases the initial rate and eliminates the lag of grana and stroma thylakoid formation after the onset of white light 60 h after sowing. The effect of a pretreatment with 15 s red light pulses is fully reversible by 756 nm light pulses. This reversibility is lost within 5 min. Evidence is presented which suggests that the time course of grana and stroma thylakoid formation is not correlated with the time course of the dispersal of the prolamellar body. The different functions of phytochrome and chlorophyll in controlling thylakoid formation are discussed.
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    URL: http://dx.doi.org/10.1007/BF00387888
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  • 17
    Electronic Resource
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    Investigations on the role of ethylene in phytochrome-mediated photomorphogenesis (1978)
    Springer
    Planta 142 (1978), S. 119-122 
    Details
    ISSN: 1432-2048
    Keywords: Chlorophyll ; Ethylene ; Phenylalanine ammonia-lyase ; Phytochrome ; Sinapis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The concept (Burg, 1973) that ethylene mediates the action of phytochrome in seedling photomorphogenesis was tested in the intact mustard (Sinapis alba L.) seedling. The effect of exogenous ethylene (100 μl l−1) on five distinct, phytochrome-mediated photoresponses of the cotyledons was investigated. It was found that anthocyanin contents (see Bühler et al., 1978) and phenylalanine ammonia-lyase levels (EC 4.3.1.5) are strongly reduced by ethylene while the capacity of chlorophyll synthesis is considerably enhanced. Levels of glutathione reductase (EC 1.6.4.2) and pools of photoconvertible protochlorophyll(ide) are unaffected by ethylene. It is concluded that these findings are incompatible with the idea that ethylene plays the role of a mediator in phytochrome-induced photomorphogenesis.
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    URL: http://dx.doi.org/10.1007/BF00385129
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  • 18
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    The relationship between phytochrome-photoequilibrium and Development in light grown Chenopodium album L. (1978)
    Springer
    Planta 142 (1978), S. 187-193 
    Details
    ISSN: 1432-2048
    Keywords: Chenopodium ; Far-red ; Photoequilibrium ; Phytochrome ; Stem extension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Chenopodium album seedlings were grown in light environments in which supplementary far-red light was mixed with white fluorescent light during various parts of the photoperiod. Both the logarithmic rate constant of stem extension and the leaf dry weight: stem dry weight ratio were linearly related to estimated phytochrome photoequilibrium (ϕ) in each treatment regime. These data are taken to be indicative of a functional link between phytochrome and development in the green plant. A layer of chlorophyllous tissue only affected the linearity between calculated ϕ and the logarithmic stem extension rate at high chlorophyll concentrations, whilst even low concentrations-equivalent to the levels found in stem tissue-caused a significant shift in measured ϕ. End-of-day supplementary far-red (FR) light induced between 0–35 per cent of the response elicited by all-day supplementary FR, whilst daytime supplementary FR (with a white fluorescent light end-of-day treatment) induced approximately 90 per cent. The ecological significance of this difference is discussed with respect to shade detection.
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    URL: http://dx.doi.org/10.1007/BF00388211
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  • 19
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    Boron — Key element in the actions of phytochrome and gravity? (1978)
    Springer
    Planta 143 (1978), S. 109-111 
    Details
    ISSN: 1432-2048
    Keywords: Boron ; Fluorescein ; Gravity ; Phytochrome ; Vigna
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Hypocotyl sections from dark-grown mung bean (Vigna radiata (L.) Wilczek) seedlings grown without boron exhibit little or no increase in the translocation of fluorescein in phloem cells following gravitational stimulation or red irradiation. In contrast, pretreatment of the hypocotyl sections with low concentrations of boric acid before red irradiation or gravitational stimulation results in a rapid increase in fluorescein movement. Mung bean root tips without boron fail to remain attached to a negativelycharged glass surface after several minutes of red irradiation. A low boron concentration in the solution induces tip attachment. The suggestion is made that boron is required to stabilize a positive electrostatic charge in the plasma membrane that is generated by the actions of phytochrome and gravity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00389059
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  • 20
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    Phytochrome involvement in the induction of resistance to dark abscission by malformin (1978)
    Springer
    Planta 141 (1978), S. 311-314 
    Details
    ISSN: 1432-2048
    Keywords: Abscission resistance ; Malformin ; Phaseolus ; Phytochrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The active portion of the visible spectrum which is required for malformin to produce leaves which are resistant to dark abscission from cuttings of Phaseolus aureus is red light. Abscission resistance was partially to almost completely lost by far irradiation prior to dark incubation. Although Ethrel, an ethylene releasing compound, stimulated dark abscission of resistant and control leaves, resistance was not lost because control leaves always abscised at a greater rate. The participation of phytochrome in the induction of abscission resistance by malformin is indicated.
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    URL: http://dx.doi.org/10.1007/BF00388349
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  • 21
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    Investigations on the role of ethylene in phytochrome-mediated photomorphogenesis (1978)
    Springer
    Planta 142 (1978), S. 109-117 
    Details
    ISSN: 1432-2048
    Keywords: Anthocyanin synthesis ; Ethylene ; Phytochrome ; Sinapis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The etiolating, intact mustard (Sinapis alba L.) seedling exhibits a distinct temporal pattern of ethylene production. Light, operating through phytochrome, increases the rate of ethylene production without changing the pattern. Ethylene production of the isolated plant parts (segments), added together, exceed the production of the intact system even if the wound effect is taken into account. There is no significant light effect on ethylene production of the segments. Phytochrome-mediated anthocyanin synthesis in the cotyledons is inhibited by ethylene. The responsiveness towards ethylene of the anthocyanin producing metabolic chain is decreased by phytochrome. As anthocyanin synthesis is only partly inhibited under saturating ethylene concentrations in the atmosphere around the seedlings (100 μl l−1), a twofactor analysis becomes feasible. This analysis leads to the result that phytochrome and ethylene show multiplicative behavior, meaning that phytochrome and ethylene act on the same metabolic sequence (leading to anthocyanin) but independently of each other, and at different sites. Therefore, the hypothesis that ethylene mediates the action of phytochrome in anthocyanin synthesis and photomorphogenesis in general appears to be inapplicable.
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    URL: http://dx.doi.org/10.1007/BF00385128
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    Spectral characteristics of phytochrome in vivo and in vitro (1978)
    Springer
    Planta 142 (1978), S. 225-228 
    Details
    ISSN: 1432-2048
    Keywords: Hordeum ; Phytochrome ; Receptor site
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The absorption maximum of the far-red absorbing form of phytochrome in the difference spectrum for phototransformation (Pfr λmax) was investigated in vivo and in in vitro pellets from dark grown Hordeum vulgare L. primary leaves. Exposure of pellets in Honda medium from tissue pre-irradiated with red light to far red light gave a Pfr λmax of 734 nm, a slightly longer wavelength than was seen in vivo (730 nm). After incubation as the red absorbing form of phytochrome (Pr) for 2 h at 0° C irradiation with red light showed that Pfr λmax had shifted to shorter wavelength (716 nm) in Honda medium. Further incubation as Pfr for 2 h at 0° C and irradiation with far red light showed that Pfr λmax had shifted to longer wavelength (726 nm). Similar shifts were also seen in other media, although the peak positions were different. Phytochrome remained pelletable throughout these experiments and Pfr λmax is compared to that of soluble phytochrome in similar media. The results are interpreted as indicating changes in molecular environment of the putative phytochrome membrane receptor site and that Pfr λmax can be used to probe the nature of this binding.
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    URL: http://dx.doi.org/10.1007/BF00388217
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    The disposition kinetics of diazepam in pregnant women at parturition (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 275-284 
    Details
    ISSN: 1432-1041
    Keywords: Diazepam ; pharmacokinetics ; pregnant women ; plasma clearance ; blood/plasma concentration ratio ; placental transfer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of diazepam has been studied in pregnant women at parturition. The plasma concentration of diazepam was monitored for at least 3 days in 18 women who received a single intravenous injection of 10 mg during the 10 h-period prior to delivery. Fourteen mothers had uneventful puerperia (Group I) and in 13 of these cases there was a pronounced postnatal increase in the plasma concentration of diazepam. The terminal phase half-life (t1/2) was significantly greater for Group I (mean = 65 h; range = 24–114 h) than for age-matched non-pregnant patients (mean = 29 h; range = 18–44 h from literature). The prolonged t1/2 appeared to be related to changes in the distribution of diazepam and not to a reduction in hepatic elimination since the total plasma clearance (Cltp) in these 14 pregnant patients (mean = 28 ml/min; range = 18–43 ml/min) was not reduced compared to that reported for non-pregnant controls (mean = 30 ml/min; range = 22–45 ml/min). Four mothers underwent postnatal surgery for tubal ligation (Group II) and the plasma concentration-time profiles for this group did not show the same postnatal phenomenon as did the profiles obtained for Group I. The t1/2 for Group II was shorter (mean = 31 h; range = 24–37 h) than for Group I and similar to that for the non-pregnant controls. The Cltp for Group II was greater (mean = 56 ml/min; range = 48–63 ml/min) than for both Group I and non-pregnant controls. These results suggest that delivery alters the disposition of diazepam and is generally associated with a postnatal re-distribution of diazepam into the systemic circulation. The blood/plasma concentration ratio was determined in 9 patients (mean = 0.62; range = 0.54–0.77). There was no difference in the total blood clearance between the pregnant patients of Group I and the non-pregnant controls. In most cases the umbilical venous plasma concentration (Cpuv) of diazepam was greater than the peripheral maternal venous plasma concentration (Cpmv) at delivery. The foetus appears to constitute a slowly equilibrating tissue-group in which diazepam does not reach equilibrium with the maternal systemic circulation for at least 5–10 h at which time the diazepam concentration in maternal and foetal plasma is similar.
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    URL: http://dx.doi.org/10.1007/BF00716363
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    Bioavailability of p-chlorophenoxyisobutyric acid (clofibrinic acid) after repeated doses of its calcium salt to humans (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 49-53 
    Details
    ISSN: 1432-1041
    Keywords: p-Chlorophenoxyisobutyric acid ; clofibrate ; steady-state plasma concentrations ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations and bioavailability of clofibrinic acid have been estimated under conditions approaching the steady-state during a ten-day period of administration as clofibrate or as a calcium clofibrinate-carbonate combination (1:1 w/w) at a dosage interval of 12 h. Formulation — related differences in bioavailability were not significant, and the 95% confidence limits of these differences were within −2% to +8% of the mean for the reference formulation of clofibrate. The mean steadystate plasma concentrations of clofibrinic acid measured on the tenth day of dosing were 116 µg/ml±22 S.D. and 119 µg/ml±23 S.D. after administration of 885 mg as clofibrate and the calcium clofibrinate-carbonate combination respectively. The peaks of mean plasma concentrations were 70 µg/ml±15 S.D., 119 µg/ml±32 S.D. and 131 µg/ml±26 S.D. on the first, fifth and tenth day of dosing with clofibrate, and 62 µg/ml±13 S.D., 127 µg/ml±S.D. and 143 µg/ml±25 S.D. on the corresponding days of dosing with the calcium clofibrinate-carbonate combination. After the last dose on the tenth day of dosing, the mean apparent half-lives of elimination of clofibrinic acid from plasma were 24.2 h±4.4 S.D. and 25.5 h±3.2 S.D. after administration of clofibrate and the calcium clofibrinate-carbonate combination respectively.
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    Metabolism of phenazone in man after hydrocortisone administration (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 69-72 
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    ISSN: 1432-1041
    Keywords: Phenazone ; pharmacokinetics ; hydrocortisone ; elimination rate ; distribution volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of a high plasma concentration of hydrocortisone on the metabolism of phenazone in humans has been studied. Two series of experiments were carried out, Group A to demonstrate any enzyme-inducing effect of hydrocortisone, and Group B to study the immediate effect of hydrocortisone on the metabolism of phenazone. 9 subjects (Group A) received a total 250–400 mg hydrocortisone i.m. twice daily for three days and the 24-hour elimination of phenazone was studied before and afterwards. In a further 5 subjects (Group B) the elimination of phenazone was examined during administration of hydrocortisone or placebo. The elimination rate and the apparent volume of distribution of phenazone remained unchanged under both experimental conditions.
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    Pharmacokinetics and side-effects of clonidine (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 97-101 
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    ISSN: 1432-1041
    Keywords: Clonidine ; plasma level ; pharmacokinetics ; steady state ; urinary excretion ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single oral dose of clonidine 300 µg was administered to 8 healthy, normotensive subjects and the time course of its plasma concentrations was followed for 24 h. The plasma concentration of clonidine rose to a peak of 1.17±0.12 ng/ml at about 2 h: the absorption half-life was 0.6±0.2 h. Elimination followed first order kinetics with a half-life of 7.7±2.0 h. The correlation between the two most common side-effects of clonidine, sedation and dryness of the mouth, with the time course of its plasma concentrations was highly significant, p〈0.01. All the subjects complained of severe sedation. During continuous administration of clonidine (75 µg t.i.d.) for one week a steady state serum level of 0.30–0.35 ng/ml was achieved. One 75 µg tablet of clonidine raised the serum level to about 0.69±0.13 ng/ml in two hours. After cessation of dosing, the serum level declined with a half-life of 7.5±1.5 h. The urinary excretion of unchanged clonidine was found to be about onethird of the administered dose in 24 h during continuous administration and in the first 24 h after the single oral dose.
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    The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 203-212 
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    ISSN: 1432-1041
    Keywords: Mepivacaine ; pharmacokinetics ; neonates ; healthy adults ; metabolism ; renal excretion ; lignocaine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and metabolism of mepivacaine has been studied in premature neonates dosed subcutaneously and in healthy adults dosed intravenously. The pharmacokinetics of mepivacaine in four neonates (N) was compared with that in six adults (A). Newborns had a significantly longer terminal phase half-life than adults (N mean 8.69 h; A mean 3.17 h). Total plasma clearance normalized on body weight was significantly smaller in neonates (mean 2.34 ml/min/kg) than in adults (mean 5.47 ml/min/kg), as was the hepatic blood clearance (N mean 1.37 ml/min/kg; A mean 5.10 ml/min/kg). The renal plasma clearance, however, was significantly greater in neonates (mean 0.76 ml/min/kg) than adults (mean 0.20 ml/min/kg). There was an average six-fold increase in the fraction of the dose excreted unchanged in newborns (mean 43.3%) compared to adults (mean 7.1%) with acidified urine (pH 5.5–6.0). There was significantly more of the mono-N-demethylated metabolite of mepivacaine excreted by newborns (mean 11.4%) than by adults (mean 2.2%), but their capacity to carry out aromatic hydroxylation of mepivacaine was negligible. These results for mepivacaine were compared with those previously reported for lignocaine in premature infants. The immaturity of hepatic function appears to have diminished more profoundly the ability of premature infants to metabolize mepivacaine than lignocaine. These findings are discussed in terms of perfusion theory of hepatic drug elimination.
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    Pharmacokinetics of high-dose methotrexate treatment in children (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 143-147 
    Details
    ISSN: 1432-1041
    Keywords: Children ; leukemia ; high-dose methotrexate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of intravenous high-dose methotrexate were studied in two groups of children being treated for malignant diseases, mostly acute lymphatic leukemia. The peak serum level of methotrexate of 2.32·10−5 mol/l was found in children given 500 mg methotrexate/m2 by a 24 h infusion, and another group given 2790 mg/m2 during a 6 h infusion had serum levels as high as 2.16·10−4 mol/l. The decay of serum concentration of methotrexate after completion of the infusion followed a diphasic curve, with an initial serum half-life of 4.8 h, followed by a second half-life of 34.4 h at distribution equilibrium. The apparent volume of distribution was 56.8 litres/m2. Significant levels of methotrexate were found in cerebrospinal fluid, but penetration into cerebrospinal fluid was slow. Urinary excretion of methotrexate was considerable. Four to five days after commencement of the infusion, urinary concentrations of methotrexate still exceeded the serum levels.
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    Binding of drugs to human muscle (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 335-340 
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    ISSN: 1432-1041
    Keywords: Drug binding to muscle ; interindividual differences ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Binding of 22 drugs to human muscle tissue has been determined by ultrafiltration. All drugs tested were bound, the bound fraction ranging from 13% (aminophenazone) to 〉98% (desipramine). Both linear and nonlinear binding was observed. For chemically related substances, binding to muscle tissue correlated with plasma binding and lipid solubility. There were significant differences in binding to muscle from different individuals. With respect to pharmacokinetics of drugs, it is suggested that binding to muscle tissue may be at least as important as plasma binding.
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    Pharmacokinetics of furosemide in anephric patients and in normal subjects (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 41-48 
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    ISSN: 1432-1041
    Keywords: Furosemide ; pharmacokinetics ; anephric patients ; metabolism ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of furosemide 40 mg i.v. were compared in 7 anephric patients and in 7 normal subjects. The average serum clearance was 66 ml/min in the patients and 219 ml/min in the normal subjects, and the corresponding weight corrected clearances were 1.33 ml/min · kg and 2.96 ml/min · kg. Binding to serum proteins was significantly decreased in the anephric subjects, in whom a significant negative correlation was found between the percentage binding and the volume of distribution VDss. In the patients, but not in the normal subjects, there was a significant positive correlation between $$V_{D_{ss} } $$ and serum clearance. Both in normal and anephric individuals 4-chlor-5-sulphamoylanthranilic-acid (CSA) was found, but there was no evidence of special accumulation either of CSA or anthranilic acid in the anephric patients. In the patients the initial increase in serum concentration of sodium and protein followed by a more conspicuous decrease were more pronounced, but none of the changes were statistically significant.
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    Pharmacokinetics of a microcrystalline theophylline preparation in patients with chronic obstructive airways disease (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 29-33 
    Details
    ISSN: 1432-1041
    Keywords: Microcrystalline theophylline ; chronic obstructive airways disease ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma theophylline concentrations have been measured in 9 patients with chronic obstructive airways disease following the oral administration of a microcrystalline theophylline preparation. Some measurements of FEV1 were also made. Four patients were given 375 mg as a single dose and then subsequently 375 mg stat and 125 mg 4 times daily for 3 days, (Group I). A further 5 patients took 250 mg as a single dose and then 250 mg 4 times daily for 3 days, (Group II). In both groups, following the single dose and again after the last dose of chronic administration, blood samples were obtained at frequent intervals up to 24 h for plasma drug estimation. During the 3-day course, blood samples were drawn before and 2 h after each morning dose. In Group I patients, substantial plasma theophylline concentrations were seen only after the loading dose. Thereafter, the mean concentrations before or 2 h after the morning doese were always less than 4.0 µg/ml. Trough concentrations were usually below 2.0 µg/ml. In contrast patients in Group II achieved substantially higher plasma theophylline concentrations, with mean peak concentrations always 10 µg/ml or greater, and trough concentrations greater than 5 µg/ml on at least one occasion in every subject. The elimination half-lives after chronic administration in both groups were not significantly different from those obtained after single doses. Mean drug accumulation, measured as AUCss/AUC1, was 0.87±0.07 in Group I and 0.72±0.14 in Group II, indicating that accumulation had not occurred with either regimen. The mean increase in FEV1 2 h after the administration of a single dose was 19.2% after 375 mg and 16.7% after 250 mg. These results indicate that the recommended dosage regimen for microcrystalline theophylline preparation (375 mg stat and 125 mg 4 times daily) produces inadequate plasma theophylline concentrations: 250 mg 4 times daily would appear to be likely to result in satisfactory theophylline levels in more patients.
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    Pharmacokinetics and metabolism of the anilide local anaesthetics in neonates. 11 etidocaine (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 365-371 
    Details
    ISSN: 1432-1041
    Keywords: Etidocaine ; pharmacokinetics ; metabolism ; neonate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary elimination of etidocaine and several of its metabolites was investigated in neonates whose mothers had received one or more doses of etidocaine during labour. The urine collection period ranged among the neonates from 21.4 to 47.0 h post-partum. The total amounts of etidocaine and its metabolites recovered in neonatal urine represented a mean of 0.12 per cent of the maternal dose. Some differences in the pattern of urinary metabolites were observed between neonates and adults. Mean half-life of elimination of etidocaine calculated from sigma-minus plots of the neonatal urinary data was 6.42 h. This is greater than that previously reported following intravenous administration of etidocaine to adults (2.6 h). The slower rate of elimination in neonates is probably due to an increased neonatal volume of distribution since there is evidence to show that etidocaine is extensively metabolised by the neonate.
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    Influence of bed rest on the pharmacokinetics of phenazone (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 379-383 
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    ISSN: 1432-1041
    Keywords: Antipyrine ; pharmacokinetics ; phenzone ; posture ; immobilization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single dose of phenazone was studied in six subjects while ambulant and during bed rest for 3 days. Elimination of the drug was followed for 12 h after oral and intravenous administration. The elimination rate constant and total body clearance were significantly increased during bed rest as compared to the ambulant period, but the differences were small. The apparent volume of distribution decreased significantly. No consistent change due to bed rest was found in the rate of absorption or bioavailability of the oral dose.
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    Paracetamol (acetaminophen) kinetics in patients with Gilbert's syndrome (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 209-212 
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    ISSN: 1432-1041
    Keywords: Paracetamol ; acetaminophen ; Gilbert's syndrome ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of paracetamol after intravenous and oral administration has been studied in 6 patients with Gilbert's syndrome, and 6 healthy controls. Paracetamol clearance was significantly less in the patients (255 ml/min SE±23 ml/min) than in the normal subjects (352 ml/min SE±40 ml/min). Moreover, whilst paracetamol concentrations declined monoexponentially in the patients, the decline was biexponential in the controls. No difference in the bioavailability of 500 mg paracetamol given orally was observed between the two groups. The results suggest that not only is paracetamol elimination impaired in Gilbert's syndrome, but that its distribution kinetics are also abnormal. Both these findings could be attributed to a decrease in hepatic glucuronyl transferase activity.
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  • 35
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    Output of14CO2 in breath after oral administration of (14C-methyl) aminopyrine in hepatitis, cirrhosis and hepatic bilharziasis: Its relationship to aminopyrine pharmacokinetics (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 223-229 
    Details
    ISSN: 1432-1041
    Keywords: Aminopyrine ; pharmacokinetics ; 14CO2 breath test ; hepatic disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time-course of aminopyrine in plasma and of14CO2 in breath was determined for 6 hours after oral administration of (14C-methyl) aminopyrine to healthy controls and to patients with hepatitis and hepatic fibrosis, cirrhosis and hepatic bilharziasis.14CO2 in breath declined about 1.8 times more slowly than aminopyrine plasma levels, which suggests the occurrence of metabolite demethylation. This was confirmed by the slow elimination of14C from plasma, the formation of14CO2 after aminopyrine had disappeared and the presence of a considerable amount of monomethyl-aminopyrine in plasma. The mean14CO2 concentration in breath was correlated with but was not proportional to aminopyrine clearance, which was attributed to individual differences in aminopyrine half-life. Both a correlation and proportionality were found when14CO2 extrapolated to zero time was used as a parameter of14CO2 production. Hepatic disease affected aminopyrine clearance to a variable extent. In the hepatitis and fibrosis group, aminopyrine clearance was affected in 2 out of five subjects. In all except one cirrhotic subject aminopyrine clearance was markedly decreased. Moreover, in three out of seven cases aminopyrine absorption was impaired, presumably due to decreased gastrointestinal blood-flow. This may produce an erroneously low14CO2 concentration in breath during the first two hours after aminopyrine administration. Hepatic bilharziasis was accompanied by very low aminopyrine clearance in all four cases. In two patients high apparent Vd values were observed, probably due to “first-pass” metabolism. Patients with ascites had Vd values within normal limits.
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    Pharmacokinetics of sulfadiazine and trimethoprim in man (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 57-67 
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    ISSN: 1432-1041
    Keywords: Chemotherapy ; sulfadiazine ; trimethoprim ; pharmacokinetics ; acetylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sulfadiazine (SDZ) 800 mg and trimethoprim (TMP) 160 mg were given orally to 10 normal subjects and the concentration of SDZ and TMP in serum and urine was followed for 24 h. Both drugs showed a significant negative correlation between individual “peak” concentrations in serum and the body weight of the subject. Twelve hours after dosing the serum concentration was 12 to 25 µg/ml for SDZ and 0.3 to 1.1 µg/ml for TMP. Individual concentration ratios between SDZ and TMP in serum were 4.8 (1 h) – 145 (24 h), and in the urine the ratio was close to 6 throughout the 24 h collection period. The range of urinary concentrations was from 65 to 400 µg/ml for SDZ and from 13.8 to 93.4 µg/ml for TMP. The fraction acetylated SDZ/acetylated SDZ + SDZ was 21% during the 0–8 h period, 33% during the 8–15 h period and 41% during the 15–24 period. The average values for the notional volume of distribution, Vd, were 0.36±0.13 1/kg for SDZ and 1.39±0.25 1/kg for TMP. The average “t1/2” was 15.2±7.4 h for SDZ and 7.4±1.9 h for TMP. Individual subjects showed a significant correlation between the serum clearance of TMP and SDZ (p〈0.01) and also between the renal clearance of the two drugs (p〈0.05). The serum clearance was significantly correlated with the renal clearance for TMP but not for SDZ. For SDZ Vd was significantly negatively correlated with the elimination constant; for TMP no such correlation was found. The serum clearance of SDZ was significantly correlated with the percentage of SDZ which was excreted as the (presumably) acetylated compound. The renal clearance of SDZ was independent of the serum concentration of SDZ. There was a highly significant negative correlation between the renal clearance and serum concentration of TMP, as well as for “acetylated SDZ”. The renal clearance of “acetylated SDZ” averaged more than six times that of unconjugated SDZ. With increased urine flow the renal clearances of TMP and SDZ were significantly increased.
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    Distribution, elimination and natriuretic effect of furosemide in patients with severe arterial hypertension (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 237-244 
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    ISSN: 1432-1041
    Keywords: Furosemide ; arterial hypertension ; protein binding ; sodium excretion ; renal function ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Furosemide 40 mg was injected intravenously in 7 patients with severe hypertension and vascular complications. A two compartment, open model was used to describe the disappearance of the drug from serum. The mean serum clearance (Cls=1.83 ml/min · kg) was significantly reduced compared to the mean Cls-value of a group of normals (2.96 ml/min · kg). A significant correlation was found between Cls and mean blood pressure, as well as between Cls and renal clearance (mean Clr=0.83 ml/min · kg); extrapolation of the regression line yielded a Cls-value of 50 ml/min for Clr=0. The Clr was also significantly negatively correlated with mean blood pressure. Protein binding of furosemide was normal, except in one patient, who had considerable impairment of renal function. Apparently more than 90% of unchanged furosemide passed in urine was excreted by tubular transport. A highly significant negative correlation was found between Cls and the fraction of furosemide excreted as a glucuronide. During the first two hours, significantly less sodium was excreted by the patients than by a comparable group of normal subjects. The correlation between serum concentration of furosemide and the amount excreted of sodium was not significant, but highly significant correlations were found between the amounts of furosemide and sodium excreted by the kidney in 0–30 and 0–60 min. In all the individual patients an approximately linear relationship with wide variation in the slope was found between the cumulative excretion of furosemide and sodium from 0–30 min to 0–60 and to 0–120 min. After 120 min deviations were observed in the curves from 4 of the patients, which indicated that smaller and smaller additional amounts of sodium were excreted with constant additional amounts of furosemide.
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    Pharmacokinetics of ordinary and sustained-release lithium carbonate in manic patients after acute dosage (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 267-271 
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    ISSN: 1432-1041
    Keywords: Lithium ; sustained-release ; pharmacokinetics ; manic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An ordinary and a sustained-release lithium carbonate preparation were administered acutely at equivalent dosage (1.80 g=24.3 mmol) in a crossover fashion to manic patients. Serum lithium levels were determined by atomic absorption spectroscopy and pharmacokinetic parameters were calculated. Maximum mean serum levels of 1.13 mmol/l and 0.78 mmol/l were achieved at 6 h and 12 h respectively with the ordinary and sustained-release forms. The mean half-lives of absorption, redistribution and elimination were 0.78 h±0.05 (SE), 5.06 h±0.23, 26.8 h±4.5 and 3.73 h±0.37 (SE), 4.42 h±0.28 and 25.6 h±5.5 for the ordinary and sustained-release forms respectively. In healthy volunteers the ordinary preparation was completely absorbed but only 85% of the sustained-release form was absorbed in the manic subjects. Lithium ion distributed into two kinetic compartments and the final compartment appeared to correspond to total body water.
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    Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 277-280 
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    ISSN: 1432-1041
    Keywords: Doxycycline ; iron ; charcoal ; enteral cycling ; man ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the intestinal interactions of doxycycline (DC) with Fe++ and charcoal, two groups of healthy volunteers were given either 200 mg or 100 mg DC in capsules at 2 p. m. and 9 p. m., and blood samples for fluorimetric assay of DC were collected for 24 h starting at 8.30 a. m. on the following morning. A 24-h-urine was also collected. The test was subsequently repeated at one-week intervals, when the volunteers also ingested either ferrous sulphate (80 mg Fe++) or charcoal (4.0 g) immediately after the zero-time sample of DC and at 3, 8 and 12 h. Charcoal completely adsorbed DC in vitro in an artificial small intestinal fluid. Ferrous sulphate or charcoal did not modify the serum level or urinary excretion of DC after the 200 mg+200 mg dose, but ferrous sulphate did reduce the 24-h urinary excretion of DC after the 100 mg+100 mg dose. The serum half-life and AUC of DC were reduced by ferrous sulphate given after the 100 mg+100 mg dose of DC. Charcoal did not modify any parameter, even after the 100 mg+100 mg dose of DC. The results do not support existence of important enteral cycling of DC. Although oral ferrous sulphate can lower the serum level and shorten the serum half-life of DC, the acute experiment suggested that a therapeutic serum level of DC can be maintained despite treatment with iron in the doses used in iron-deficiency, and charcoal in the doses used in diarrhoeic states, if the drugs are administered several hours apart.
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    Preliminary studies of the kinetics of citalopram in man (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 69-73 
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    ISSN: 1432-1041
    Keywords: Citalopram ; pharmacokinetics ; man ; steady state levels ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of citalopram, a potent serotonin reuptake inhibitor, and its demethylated metabolite have been determined by a specific fluorescence coupling technique during single dose experiments in volunteers and in clinical tests. Citalopram was found to have linear kinetics within the dose range investigated, which were characterized by fairly rapid absorption and slow elimination (biological half-life 1–21/2 days). Steady state levels in the range 120–340 nM (i.e. slightly above those associated with pharmacodynamic activity in animals) were attained within a week. A drug/metabolite ratio of 2–3 was recorded.
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    Plasma timolol levels after oral and intravenous administration (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 431-434 
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    ISSN: 1432-1041
    Keywords: Timolol ; pharmacokinetics ; oral and intravenous dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma kinetics of timolol administered orally and intravenously to 5 male subjects were examined. Bioavailability was reduced by 25% when the drug was taken orally. Mean plasma half-life after oral dosing was 4.86 h, and after intravenous administration it was 4.56 h; the difference was not significant. The volume of distribution was 3.5 l/k. It is suggested that timolol is little affected by the ‘first pass effect’, even though there is marked interindividual variation in availability and peak plasma level.
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    The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 143-152 
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    ISSN: 1432-1041
    Keywords: Lignocaine ; pharmacokinetics ; neonates ; metabolism ; renal excretion ; plasma concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and metabolism of lignocaine in premature neonates was studied after subcutaneous administration. The collection of serial urine together with a limited number of blood samples from neonates enabled simultaneous computer fitting of data to a pharmacokinetic model. The disposition kinetics of lignocaine in four neonates were compared with similar data reported for adults. Neonates had prolonged t1/2 (neonate mean: 3.16 h; adult mean: 1.80 h), and an increased total volume of distribution (neonate mean: 2.75 l/kg; adult mean: 1.11 l/kg) compared with adults. Total plasma clearance (Cltp) normalised on body weight showed no significant difference between neonates (mean: 0.610 l/h/kg) and adults (mean: 0.550 l/h/kg). The urinary excretion of lignocaine and several of its metabolites was studied in 8 neonates and 11 adults. Neonates were shown to excrete much more unchanged lignocaine (mean: 19.67%) compared with adults (mean: 4.27%) and the proportion of the dose excreted as 4-hydroxyxylidine is considerably reduced in neonates (neonate mean: 8.89%; adult mean: 63.78%). The use of the two pharmacokinetic parameters, t1/2 and Cltp, as indices of drug elimination ability are discussed.
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    Preliminary data on the pharmacokinetics of Glaziovine in man (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 219-222 
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    ISSN: 1432-1041
    Keywords: Glaziovine ; pharmacokinetics ; plasma levels ; urinary excretion ; biliary excretion ; enteral absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of Glaziovine, a pro-aporphine alkaloid with neuropharmacological properties, were investigated in healthy human volunteers. Glaziovine-14C 20 mg was administered in capsules (oral route) and in vials (i.v. route). Total radioactivity was measured in plasma, urine and faeces. When administered orally, peak plasma levels were encountered at 2 h. The cumulative urinary excretion of total radioactivity over a 24 h period was 38% after oral and 50% after i.v. administration. Investigation of metabolites in urine revealed Glaziovine glucuronide as the sole metabolite of the drug. By comparing the percentage of urinary excretion or the area under the plasma level-time curve (AUC) obtained in the first 24 hours after i.v. and oral administration, enteral absorption was found to range from 78 to 84%. Thus, glaziovine appears to show very high enteral absorption.
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    Disposition of valproic acid in patients with liver disease (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 55-60 
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    ISSN: 1432-1041
    Keywords: Valproic acid ; pharmacokinetics ; liver disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of valproic acid (di-n-propylacetate; VA) has been studied after a single oral dose of a solution of 450 mg in 7 patients with alcoholic cirrhosis and in 4 patients recovering from acute hepatitis. The diagnosis was based on biochemical function tests and histological findings. The pharmacokinetic parameters were compared with those reported for healthy volunteers. VA in therapeutic concentration (80 µg/ml) in plasma was less bound to plasma proteins in patients with alcoholic cirrhosis (70.7±11.3%) and in patients recovering from acute hepatitis (78.1±14.1%) than in controls (88.7±5.2%). The reduced binding affected the blood/plasma concentration ratio and the apparent distribution volume Vd(β); the latter was increased from the normal value of 0.14±0.05 l/kg to 0.22±0.09 (p〈0.05) in alcoholic cirrhotics, and to 0.20±0.07 (p=0.056) in patients recovering from acute hepatitis. The half-life of elimination T1/2 (β) (controls=12.2±3.7 h) was significantly (p〈0.05) prolonged in cirrhotics (18.9±5.1 h) and in patients recovering from acute hepatitis (17.0±3.7 h). The plasma $$\overline {Cl} $$ of total drug was not impaired, which can best be explained by the lower plasma protein binding, which might have increased the $$\overline {Cl} $$ of this drug which shows restricted clearance. In addition, the plasma $$\overline {Cl} $$ of free drug was significantly (p〈0.02) reduced in alcoholic cirrhotics. During a two day urine collection no measurable amount of unchanged VA was recovered. There was considerable excretion of VA-conjugates, which could be hydrolyzed either by HCl or by β-glucuronidase/arylsulphatase (4–23% of the dose). These percentages were in the same range as in normals (26.7±16.1%). The study indicates that elimination of VA is slightly impaired in patients with dysfunction of the liver.
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    Absorption of oral and intramuscular chlordiazepoxide (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 267-274 
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    ISSN: 1432-1041
    Keywords: Chlordiazepoxide ; benzodiazepines ; pharmacokinetics ; bioavailability ; intramuscular injection ; alcohol withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of oral and intramuscular (i. m.) chlordiazepoxide hydrochloride (CDX · HCl) was compared in two pharmacokinetic studies. In Study One, single 50-mg doses of CDX · HCl were administered orally and by i. m. injection to 14 healthy volunteers using a crossover design. Whole-blood concentrations of chlordiazepoxide (CDX) and its first active metabolite, desmethylchlordiazepoxide (DMCDX), were determined in multiple samples drawn after the dose. Mean pharmacokinetic variables for CDX following oral and i. m. administration, respectively, were: highest measured blood concentration, 1.65 vs 0.87 µg/ml (p〈0.001); time of highest concentration, 2.3 vs 7.6 h after dosing (p〈0.001); apparent absorption half-life, 0.71 vs 3.39 h (p〈0.001). Biphasic absorption after i. m. injection, consistent with precipitation at the injection site, was observed in 9 of 14 subjects. Based upon comparison with previous intravenous data, the completeness of absorption was 100% for oral vs 86% for i. m. CDX · HCl (p〈0.1). In Study Two, 28 male chronic alcoholics with clinical manifestations of the acute alcohol withdrawal syndrome were randomly assigned to one of four treatment conditions: 50 or 100 mg doses of CDX · HCl, by mouth or by i. m. injection. Concentrations of CDX and DMCDX, determined in plasma samples drawn every 20 min for 5 h following the dose, were significantly higher after oral administration of a given dose than at corresponding points in time after i.m. injection after the same dose. Thus absorption of oral CDX is reasonably rapid and complete, whereas the absorption rate of i. m. CDX is slow.
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    Model for retrospective estimation of serum levels of phenylbutazone: Application to two cases of digestive tract hemorrhage (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 439-443 
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    ISSN: 1432-1041
    Keywords: Phenylbutazone ; pharmacokinetics ; model ; retrospective analysis ; digestive-tract hemorrhage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Phenylbutazone treatment can cause digestive-tract hemorrhages, but its concentration in the blood at the time of hemorrhage is generally not known. In two patients who had had digestive tract hemorrhages, the variation in the serum phenylbutazone concentration throughout treatment and just before hemorrhage was simulated by a two-compartment model based on assays (gas-liquid chromatography) made after the hemorrhage. Identification of the parameters of the model and simulation of changes in concentration during therapy suggested that the phenylbutazone level in serum at the time of hemorrhage was 101 and 125 µg/ml respectively.
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    Pharmacokinetics of a single oral dose of hydroflumethiazide in health and in cardiac failure (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 29-37 
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    ISSN: 1432-1041
    Keywords: Hydroflumethiazide ; pharmacokinetics ; cardiac failure ; renal drug excretion ; metabolism ; 2,4-disulfamyl-5-trifluoro-methylaniline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of hydroflumethiazide (HFT) were investigated after single oral doses of 6 µmoles/ per kg body weight in five healthy subjects and in nine patients with moderate cardiac failure. HFT was excreted in urine together with 2,4-disulfamyl-5-trifluoromethylaniline (DTA), which was also present in the blood after administration of HFT. HFT and DTA were determined by TLC and spectrofluorodensitometry. Mean cumulative urinary excretion of HFT was 46.5 and 47.5 per cent of the dose both in healthy subjects and in patients. Distribution half-life (t1/2α) was about 2 h in both groups of subjects, while biological half-life (t1/2β) ranged from 12.4 to 26.9 h (mean 16.6) in healthy subjects, and from 6.3 to 13.7 h (mean 9.6) in patients. Mean renal clearance was 0.33 and 0.211 · h−1 · kg−1 in normal subjects and patients, respectively, and was almost equal to the total body clearance. HFT had a large apparent volume of distribution (Vβ), with mean values of 6.4 and 3.11 · kg−1 in normal subjects and patients. Mean cumulative urinary excretion of DTA was 1.8 and 1.9 per cent in healthy subjects and patients with cardiac failure. The apparent half-life of DTA, determined from urinary excretion rate in eleven subjects, ranged from 16 to 56 h but half-lives in three others were more than 100 h. The results indicate that HFT is partly metabolized in the body to DTA, and DTA and HFT are excreted in urine. The half-life of DTA was longer than that of the parent drug. The apparent volume of distribution, clearance and biological half-life of HFT were lower in patients with cardiac failure than in healthy subjects.
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    Pharmacokinetics of furosemide in gestosis of pregnancy (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 361-366 
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    ISSN: 1432-1041
    Keywords: Furosemide ; gestosis of pregnancy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Furosemide 50 mg was administered orally and intravenously to twelve gestotic women for brief periods as a part of a randomized, multicentre clinical trial comparing the efficacy of bed rest and pharmacological treatment. The pharmacokinetic profile was investigated using a gas-liquid chromatographic technique. The plasma half-life after oral and intravenous administration was 115±37.1 and 71.8±26.3 min and plasma clearance was 153±48 and 152±23 ml/min, respectively (mean±SD). Comparative data from healthy pregnant women cannot be obtained for ethical reasons. The results show that gestosis has only a marginal if any effect on the kinetics of furosemide in comparison with published kinetic parameters in healthy volunteers and patients with renal failure. The new-born babies where checked for side effects according to a protocol in use in a larger regional surveillance programme. No clinical side-effects were attributable to furosemide, but the small size of the group does not permit any definitive conclusions about this aspect.
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    Clinical pharmacology in normal volunteers of praziquantel, a new drug against schistosomes and cestodes (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 281-291 
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    ISSN: 1432-1041
    Keywords: Phase I clinical trial ; complex protocol ; tolerance ; pharmacokinetics ; praziquantel ; anthelmintic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The tolerance of Praziquantel (2-cyclohexylcarbonyl-1, 3, 4, 6, 7, 11b-hexahydro-2H-pyrazino-[2, 1-a]isoquinoline-4-one) in oral doses of 1×20 mg/kg, 1×50 mg/kg, 3×10 mg/kg and 3×25 mg/kg body weight (τ=4 h) was tested in a complex study involving 36 healthy volunteers. In addition to the usual assessment of clinical chemistry, haematology, coagulation physiology, urinalysis, clinico-physiological examination including EEG, and medical examination, clinico-psychological parameters were also recorded and special neurological investigations were performed. No clinically relevant changes were found in any of the laboratory parameters, nor in the medical-neurological or clinico-physiological examinations. Based on a few clinicopsychological parameters and subjective comments, the largest daily dose tested (3×25 mg/kg=75 mg/kg) produced a slight, transient disturbance in general well-being, which was barely detectable on objective clinical examination. The pharmacokinetic behaviour was dominated by rapid metabolism and pronounced first-pass metabolism of praziquantel, which greatly limits the value of results obtained by GC analysis of unchanged drug in serum. The peak concentration in serum was reached after 1– h, and the elimination half-life for the period 2–8 h was 1–1.5 h.
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    Bioavailability of norethindrone in human subjects (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 35-39 
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    ISSN: 1432-1041
    Keywords: Norethindrone ; bioavailability ; man ; competitive protein binding ; sex differences ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.
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    Pharmacokinetics of bendroflumethiazide in hypertensive patients (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 119-124 
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    ISSN: 1432-1041
    Keywords: Bendroflumethiazide ; pharmacokinetics ; hypertension ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After four weeks on placebo treatment, 8 hypertensive patients (WHO stage I) were treated for 2 weeks with bendroflumethiazide (bft) 2.5 mg and KCl 1.5 g daily. Subsequently they received bft 5 mg and KCl 1.5 g daily for a further fortnight. At the end of each period of treatment blood pressure was recorded and blood samples and urine were collected for analysis of bft by GLC. Before taking the daily dose of bft, no trace of the drug was found in plasma. Peak levels of bft were seen after 2.3 h and averaged 23 and 50 ng · ml−1 after 2.5 and 5 mg, respectively. After bft 2.5 mg the plasma level was too low for kinetic analysis. The plasma half-life after 5 mg averaged 4.1 h. The mean apparent volume of distribution was 1.18 l · kg−1. Non-renal clearance averaged 200 ml · min−1. The renal clearance of bft was significantly lower (p〈0.05) after 5 mg (48 ml · min−1) than after 2.5 mg bft (93 ml · min−1), although the creatinine clearance remained unchanged. No correlation was found between the plasma level of bft and its effect on blood pressure.
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    Pharmacokinetics of cephacetrile in patients with normal or impaired renal function (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 445-448 
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    ISSN: 1432-1041
    Keywords: Cephacetrile ; pharmacokinetics ; renal Impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cephacetrile, administered as a single i. v. injection of 15 mg/kg, have been determined in 8 patients with normal renal function and in 12 patients with a varying degree of renal impairment. A two-compartment model was used to describe the biphasic decline in serum concentrations and to calculate the amount of antibiotic in the central and peripheral compartments. In patients with normal renal function the following values were obtained for various pharmacokinetic parameters: α=3.971 h−1; β=0.343 h−1; K12=1.745 h−1; K21=0.763 h−1; Kel=1.793 h−1; Vc=8.181; Vp=18.401 and Vdss=26.581. Cephacetrile had some of the highest apparent distribution volumes of all the cephalosporins. Impaired renal function significantly affected α, β, K12, and Kel. A linear relationship between Kel of cephacetrile and creatinine clearance was demonstrated. The elimination of cephacetrile in anuric patients was about ten times slower than in patients with normal renal function.
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    Rate of drug metabolism in man measured by14CO2-breath analysis (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 293-299 
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    ISSN: 1432-1041
    Keywords: Breath analysis ; 14CO2 exhalation ; drug metabolism ; glycodiazine ; liquid chromatography ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Exhalation of14CO2 in breath has been used to assess the rate of hepatic demethylation of (14C-dimethyl)aminopyrine, but due to the complexity of aminopyrine metabolism the pharmacokinetics of the procedure are insufficiently understood. Therefore, studies were performed in five individuals after oral administration of (14C-methoxy)glycodiazine, a model substance with relatively simple kinetic properties. Plasma concentrations of the drug and urinary output of its metabolites measured by high pressure liquid chromatography were analysed by a two-compartment open model. The terminal disappearance of14CO2 from breath was practically identical with the terminal disappearance of glycodiazine from plasma, which could be correlated with the plasma clearance of free glycodiazine. The mean transit time of14C-atoms from plasma to breath was 3 h. These results contribute to the pharmacokinetic basis for use of14C-demethylation breath tests. In particular, they are consistent with the hypothesis that14CO2-breath analysis may be used to assess certain pharmacokinetic parameters of appropriately labelled test compounds. These parameters may not necessarily be a direct reflection of the rate of demethylation.
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    Elimination of hexamethylene diisocyanate cross-linked polypeptides in patients with normal or impaired renal function (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 405-412 
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    ISSN: 1432-1041
    Keywords: Colloidal plasma substitutes ; cross-linked polypeptides ; Haemaccel® ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Infusions of 3.5% isocyanate cross-linked polypeptide solution 500 ml were given to 52 patients with normal or impaired renal function: glomerular filtration rate (GFR)=0–133 ml/min. The serum concentration and urinary excretion of hydroxyproline were measured and the equivalent polypeptide concentrations were calculated from the results. In patients with normal renal function (GFR〉90 ml/min) the proportion of polypeptide excreted in the urine up to 12 h was 45.4±2.6% ( $$\bar X$$ ±SEM), up to 24 h 47.7±2.9% and up to 48 h 49.3±3.4%. In patients with moderate renal insufficiency (GFR=30–90 ml/min) there was no decrease in polypeptide excretion and even in patients with more serious impairment of GFR (11–30 ml/min) 48-h urinary polypeptide excretion was still 40.6±5.9%. In patients with GFR of 2–10 ml/min polypeptide excretion fell to 10.7±3.2% during the first 12 h, although there was an increase in later collection periods as compared to patients with normal renal function −19.9±3.9% in 24 h and 27.0±3.5% in 48 h. The elimination half-life (t1/2) calculated from serum concentrations was 505±30 min ( $$\bar X$$ ±SEM) in patients with normal renal function (GFR〉90 ml/min). Only when the GFR fell below 30 ml/min did it slowly begin to increase. In patients with minimal residual renal function (GFR=0–0.5 ml/min), who were on haemodialysis, the elimination half-life was 985±49 min, i.e. approximately twice the normal. Twice weekly infusion of 3.5% polypeptide solution 500 ml over a period of 6 weeks did not produce any significant cumulation in haemodialysis patients (GFR=0–0.5 ml/min). A weekly dose of polypeptide 35 g appeared to be quite safe when given for several weeks, even to anuric patients. As no significant amount of polypeptide was lost during haemodialysis, the dose can be chosen without taking into account any effect of intermittent haemodialysis.
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    Pharmacokinetic interpretation of the enterohepatic recirculation and first-pass elimination of morphine in the rat (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 505-519 
    Details
    ISSN: 1573-8744
    Keywords: morphine ; first-pass elimination ; pharmacokinetics ; enterohepatic recirculation ; availability ; routes of administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Morphine was administered to rats by oral, intraportal, and intravenous routes in a dose of 7.6 mg · kg −1.From the serum concentration data after intraportal administration it was calculated that the first-pass elimination of morphine in the liver amounts to 72±2% (sd). The first-pass fraction eliminated after oral administration was 85±7% (sd), thus yielding a contribution by the gut mucosa of 46% to the overall first-pass elimination after an oral dose. The results were obtained with a general compartmental model which included the kinetics of enterohepatic recirculation. The oral availability was also estimated with the aid of pharmacological effect data. This availability was in good agreement with the corresponding value determined from the serum concentration data. The results suggest that morphine is subjected to enterohepatic recirculation and that the slowest phase of decline of morphine concentrations in serum might be due to this physiological process.
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    Linear systems analysis in pharmacokinetics (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 265-282 
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    ISSN: 1573-8744
    Keywords: pharmacokinetics ; linear systems analysis ; in vivo dissolution rates ; absorption rates ; metabolic rates ; bioavailability ; numerical desconvolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The application of certain aspects of linear systems analysis to pharmacokinetic-problems is described. Topics covered include the evaluation of in vivodissolution rates, absorption rates, and metabolic rates, and the use of pharmacological data. Relevant numerical procedures are also discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01312266
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    Pharmacokinetic analysis of percutaneous absorption; evidence of parallel penetration pathways for methotrexate (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 315-325 
    Details
    ISSN: 1573-8744
    Keywords: percutaneous penetration ; methotrexate ; compartmental models ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Compartmental models were developed to describe the penetration of a drug from a topically applied vehicle through the skin. Data for in vitro penetration of methotrexate through hairless mouse skin from vehicles varying in PH from 3.5 to 6.5 were computer- fitted to estimate model parameters. Comparison of lag time and the exponential coefficient suggested that parallel penetration pathways exist. The fraction of drug penetrating through the shunt pathway increased as vehicle pH and ionization increased. Penetration curves were quantitatively partitioned into bulk tissue and shunt contributions. At pH 6.5, flux through the shunt pathway predominated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01060095
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    Mathematical prediction of drug distributionin vivo: Studies with doxantrazole in rats (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 521-537 
    Details
    ISSN: 1573-8744
    Keywords: compartmental analysis ; doxantrazole ; drug distribution ; mathematical prediction ; pharmacokinetics ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A pharmacokinetic model incorporating 14 compartments and 29 transfer coefficients has been developed from experimental data obtained after intravenous administration of a single dose to describe the distribution of doxantrazole in the rat. The distribution calculated from the model agreed closely with that determined experimentally. In addition, the model was able to predict with considerable accuracy the distribution of doxantrazole after repeated dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062107
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    Chlorpromazine metabolism. IX. Pharmacokinetics of chlorpromazine following oral administration in man (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 187-196 
    Details
    ISSN: 1573-8744
    Keywords: Chlorpromazine ; pharmacokinetics ; oral absorption ; single dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A single oral dose (120 mg/m2) of Chlorpromazine hydrochloride was administered to four healthy subjects and the blood levels of Chlorpromazine were determined with time. Appropriate equations describing the two-compartment open model with zero-order absorption and the two-compartment model with first-order absorption, both with a lag time, were fitted to the observed data using weighted nonlinear least-squares regression analysis. Fitting the two-compartment model with zero-order absorption and a lag time to the observed data resulted in a significant reduction of the weighted sum of squared deviations, i.e., better correlation between the observed and calculated data, and a closer random scatter of the observed concentration data around the calculated curve with no apparent systematic deviations from the curve. These results suggest that Chlorpromazine absorption is zero order. Chlorpromazine began to appear in the systemic circulation after a mean lag time of 0.4 hr and continued to be absorbed for approximately 2.9 hr. The mean half-lives of the distribution and elimination phases were 1.63 and 17.7 hr, respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01312261
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    Statistical moments in pharmacokinetics (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 547-558 
    Details
    ISSN: 1573-8744
    Keywords: statistical moments ; network theory ; pharmacokinetics ; bioavailability ; deconvolution ; plasma concentration-time curve ; urinary excretion rate-time curve ; compartment models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Statistical moments are parameters that describe the characteristics of the time courses of plasma concentration (area, mean residence time, and variance of residence time) and of the urinary excretion rate that follow administration of a single dose of a drug. The relationship between the moments of a time-course curve and pharmacokinetic profiles of drug disposition, i.e., absorption, distribution, metabolism, and excretion, is described. The moments are related to the extent and rate of bioavailability, and it is shown that they can be effectively applied to the deconvolution operation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062109
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    Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level-time curve (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 539-546 
    Details
    ISSN: 1573-8744
    Keywords: trapezoidal rule ; area under the curve ; pharmacokinetics ; clearance ; bioavailability ; integration method ; sulfisoxazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The linear trapezoidal rule method is commonly used for the estimation of the area under the plasma level-time curve. Error analyses are performed when the method is used in first-order absorption and first-order elimination kinetics in the one-compartment system. It is found that significant underestimations and overestimations in area during the absorption phase and postabsorption phase, respectively, can occur when the method is improperly used. During the exponential postabsorption phase the relative error is only a function of the ratio (n)of the time interval over the half-life of the two plasma data points in the interval. The error from the linear trapezoidal rule method at n=0.5 is about 1%. The error increases to 15.5% and 57.1 % when nis increased to 2 and 4, respectively. It is recommended that for most absorption studies the linear trapezoidal method be used for prepeak and plateau plasma data and the logarithmic trapezoidal method for postpeak plasma data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062108
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    Absorption of oral tetracycline in patients with Billroth-II gastrectomy (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 295-303 
    Details
    ISSN: 1573-8744
    Keywords: tetracycline ; antibiotics ; Billroth-II gastrectomy ; gastrectomy ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The bioavailability of a single 250-mg oral dose of tetracycline hydroghloride was studied in seven patients following Billroth-II gastrectomy in comparison with seven control subjects matched for age and body weight. There were no significant differences between control subjects and gastrectomized patients in the apparent lag time prior to the start of absorption (23.6 vs. 22.8 min), peak serum tetracycline concentration (1.72 vs. 1.75 μg/ml), the time of attainment of peak concentrations (3.35 vs. 3.42 hr), the apparent first-order absorption half-life (1.8 vs. 1.4hr), or the apparent first-order elimination half-life (8.0 vs. 8.7hr). Completeness of tetracycline absorption, as judged by area under the 24-hr serum concentration curve, did not differ significantly between the two groups, nor did 24-hr urinary excretion of tetracycline. Thus the abnormalities of gastrointestinal structure and function produced by Billroth -II gastrectomy do not result in impairment of the rate and completeness of tetracycline absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01060093
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    Disposition kinetics in dogs of diethyldithiocarbamate, a metabolite of disulfiram (1978)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 6 (1978), S. 369-387 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; dog ; diethyldithiocarbamate metabolite of disulfiram ; presence of methyl ester ; kinetic evaluation of prior studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Following the intravenous infusion of sodium diethyldithiocarbamate to dogs, the disposition kinetics of diethyldithiocarbamate (DDC), a metabolite of disulfiram, were assessed. Approximately 27% of the administered dose was S-methylated, this process exhibiting a mean first-order rate constant of 0. 0569 min−1 (t1/2=12.2 min), while the remainder was eliminated by other routes having a rate constant of 0.148 min−1 (t1/2=4.68 min). The methyl diethyldithiocarbamate (MeDDC) formed from DDC showed an elimination rate constant of 0.0141 min−1 (t1/2=49.2 min). These observations are discussed in the light of previous investigations where the presence of MeDDC has rarely been sought or reported. A few comparisons with prior studies, in which DDC or disulfiram was administered, are made by retrospective kinetic evaluation of published data. The results are discussed in relation to the duration of action of disulfiram in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062720
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