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  • Rat  (599)
  • Immunocytochemistry  (357)
  • bioavailability  (238)
  • Springer  (1.163)
  • American Chemical Society
  • 1985-1989  (565)
  • 1980-1984  (455)
  • 1970-1974  (143)
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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nutrition 22 (1983), S. 185-194 
    ISSN: 1436-6215
    Schlagwort(e): sugar substitutes ; D-glucose ; bioavailability ; D-glucitol (D-sorbitol) ; D-mannitol ; Palatinit® ; D-glucosyl-α(1→1)-D-mannitol ; D-glucosyl-α(1→6)-D-glucitol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Zur Vertiefung des Verständnisses vom Stoffwechsel des Zuckeraustauschstoffes Palatinit® wurden seine zwei Bestandteile D-Glucosyl-α(1→1)-D-mannit und D-Glucosyl-α(1→6)-D-glucit [D-Glucosyl-α(1→6)-D-sorbit] nach dem Verfahren von Karimzadegan et al. auf ihre Glucose-Bioverfügbarkeit an ketotischen Ratten untersucht. Bei Umwandlungsraten in Glucose von 6 bzw. 20 % für Mannit und Glucit (Sorbit) sowie von 39 bzw. 42% für Glucosylmannit und Glucosylglucit erhält demnach der metabolische Glucose-Pool nicht das volle Glucose-Äquivalent aus diesen Verbindungen. Von dem Anteil an präformierter Glucose in den Glucosylhexiten — theoretisches Maximum 50 % — sind nur 36 % aus Glucosylmannit bzw. 32 % aus Glucosylglucit bioverfügbar. Die im Vergleich zur Theorie verminderte Bioverfügbarkeit von Glucose aus Palatinit® wird auf partiellen mikrobiellen Abbau in unteren Darmabschnitten zurückgeführt. Die an Ratten erhaltenen Ergebnisse werden auch für alle anderen Spezies gelten, welche in Caecum und/oder Colon Kohlenhydrate vergären. Die Unterschiede zwischen D-Glucosyl-α(1→1)-D-mannit und D-Glucosyl-α(1→6)-D-glucit werden durch unterschiedliche Verzögerung der Glucoseresorption im Dünndarm, wo auch D-Glucit angreift, bedingt. Die Ermittlung der Glucose-Bioverfügbarkeit gewährt weitgehende Einblicke in das Schicksal von Kohlenhydraten einschließlich der Symbiose zwischen Säugetier und Mikroorganismen im Dickdarm. Da ein ziemlich vollständiger Überblick über die metabolischen Konsequenzen nach ihrer Zufuhr erhalten wird, sollte das Verfahren zur Messung der Bioverfügbarkeit von Glucose daher bei Abschätzungen der Lebensmittelsicherheit anderer Zuckeraustauschstoffe ebenfalls angewandt werden.
    Notizen: Summary For the sake of metabolic insight into the fate of the sugar substitute Palatinit®, its two components D-glucosyl-α(1→1)-D-mannitol and D-glucosyl-α(1→6)-D-glucitol [D-glucosyl-α-(1→6)-D-sorbitol] were assayed for glucose bioavailability by the procedure of Karimzadegan et al. using ketotic rats. With conversion rates into glucose of 6 and 20 %, respectively, for free mannitol and glucitol (sorbitol), 39 % for glucosylmannitol and 42 % for glucosylglucitol, the metabolic glucose pool of the rat does not receive the full carbohydrate complement of these compounds. The preformed glucose moiety of the glucosylhexitols is bioavailable by 36 and 32 %, respectively, from glucosylmannitol and glucosylglucitol, with 50 % as theoretical maximum. Less than theoretical bioavailability of glucose from Palatinit® is ascribed to microbial attack in the hindgut. The data on rats are held valid also for other species demonstrating carbohydrate fermentation in the caecum and/or colon. Differences between D-glucosyl-α(1→1)-D-mannitol and D-glucosyl-α(1→6)-D-glucitol are caused by a differential delay of glucose absorption in the small intestine, also exerted by D-glucitol. The deep metabolic insight offered by the glucose bioavailability assay into the fate of carbohydrates includes the mammal-microbial symbiosis in the large bowel. Since a rather complete survey of the metabolic consequences after their intake can be obtained, the assay system should be generally applied in assessments of food safety also of other sugar substitutes.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    ISSN: 1435-604X
    Schlagwort(e): Brain tumour ; Rat ; Detection ; Fluorescence ; Laser ; Haematoporphyrin derivative
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin , Physik , Technik allgemein
    Notizen: Abstract Laser-induced fluorescence has been used for the identification of brain tumours in rats, which have been previously given tumour-seeking haematoporphyrin derivative. A pulsed nitrogen laser (λ=337 nm) was used in conjunction with an optical multichannel analyzer. For both inoculated RG-2 and TCVC rat-brain-tumour models, the blue autofluorescence was strongly reduced in the tumour compared with normal brain tissue, and at the same time the characteristic red-drug signal increased. The contrast between tumour and normal tissue was strongly enhanced by forming the ratio between the two signals. Implications for possible improvement of tumour delineation in brain tumour surgery are discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1004-1006 
    ISSN: 1420-9071
    Schlagwort(e): Rat ; adrenocortical responsiveness ; ACTH ; plasma ; corticosterone ; plasma ; corticotropin releasing factor (CRF)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary In the course of studying the plasma adrenocorticotropic hormone (ACTH) and corticosterone responses to synthetic corticotropin releasing factor (CRF), we noted some disparity in the responses. A higher dose (20 μg compared with 5 μg per rat i.a.) produced an equal plasma ACTH but greater plasma corticosterone response in adult male rats. Thus, we examined the possibility that CRF increases adrenocortical responsiveness to ACTH. CRF significantly (p〈0.0005) increased the plasma corticosterone response to ACTH in rats pretreated with dexamethasone. Thus, synthetic CRF increases corticosterone secretion in rats not only by stimulating ACTH secretion, but also by increasing the adrenocortical responsiveness to ACTH.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 41 (1985), S. 1554-1557 
    ISSN: 1420-9071
    Schlagwort(e): Immunocytochemistry ; neuropeptide Y ; radioimmunoassay ; rat pancreas
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Significant quantities of a newly discovered peptide, neuropeptide Y, were found in the rat pancreas, where they were localized to nerves in the exocrine parenchyma and around arterial and ductal structures. Although unaffected by surgical parasympathectomy, the periarterial and periductal nerves were abolished by chemical sympathectomy, suggesting that NPY is partially costored with sympathetic transmitters in nerve fibers.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 41 (1985), S. 265-266 
    ISSN: 1420-9071
    Schlagwort(e): Rat ; hydrochlorothiazide ; pain threshold ; antinociceptive activity ; analgesic activity ; morphine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Hydrochlorothiazide, acutely injected in rats, has a weak analgesic activity per se and potentiates and prolongs the antinociceptive effect of morphine.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 40 (1984), S. 974-975 
    ISSN: 1420-9071
    Schlagwort(e): Rat ; prostaglandins ; gastric lesion ; intragastric distension model ; stress model ; indomethacin ; somatostatin preventive effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatostatin preventive effect on the gastric lesions induced in a stress model and has no preventive effect on an intragastric distension model.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 10 (1972), S. 238-251 
    ISSN: 1432-0827
    Schlagwort(e): Growth ; Bone ; Rat ; Tetracycline
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Beschreibung / Inhaltsverzeichnis: Résumé La vitesse de croissance normale en longueur de la métaphyse proximale du tibia est déterminée chez le rat Sprague-Dawley entre les âges de 20 et 100 jours, en utilisant la méthode à la tétracycline. Le taux de croissance ne varie que légèrement dans les groupes d'âges différents. Il est plus élevé chez les animaux jeunes et décroit considérablement en fonction de l'augmentation de l'âge. Les rats mâles présentent une croissance plus élevée que les femelles. Cette étude a pour but de mettre au point une méthode permettant de déterminer les facteurs expérimentaux, liés à la croissance en longueur du rat.
    Kurzfassung: Zusammenfassung Die normale Längenwachstums-Geschwindigkeit der proximalen Wachstumsplatte der Tibia wurde bei Sprague-Dawley-Ratten in einem Alter zwischen 20 und 100 Tagen mittels der Tetracyclinmethode gemessen. Die Wachstumsgeschwindigkeit variierte nur wenig innerhalb der einzelnen Altersgruppen. Die Geschwindigkeit war bei jungen Tieren am höchsten und nahm mit zunehmendem Alter beträchtlich ab. Männliche Ratten wuchsen schneller als weibliche. Diese Arbeit dient als Grundlage, um die experimentelle Beeinflussung des Längenwachstums der Ratte abschätzen zu können.
    Notizen: Abstract The rate of normal growth in length from the proximal growth plate of the tibia in the Sprague-Dawley rat was measured between 20 and 100 days of age using the tetracycline method. The growth rate varied only slightly within different age groups. The rate was highest in young animals and decreased considerably with increasing age. Male rats grew faster than female. This study is intended to provide a base for an evaluation of experimental influence on the growth in length of the rat.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 12 (1973), S. 313-321 
    ISSN: 1432-0827
    Schlagwort(e): Cathepsin D ; Extracellular ; Ossification ; Immunocytochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Beschreibung / Inhaltsverzeichnis: Résumé De la cathepsine D extracellulaire d'origine principalement ostéoblastique a été démontrée par immunohistochimie dans le cartilage en voide de calcification de cultures d'os des membres d'embryons de poulet. L'intérêt de ce fait pour l'ossification est discuté.
    Kurzfassung: Zusammenfassung Es wurde mit einer immunohistochemischen Methode gezeigt, daß extrazelluläres Kathepsin D, welches hauptsächlich aus Osteoblasten gewonnen wurde, Knorpel von kultivierten Knochen von Kükenembryonen mineralisiert. Die Bedeutung dieser Feststellung für den Mechanismus der Knochenbildung wird diskutiert.
    Notizen: Abstract Extracellular cathepsin D derived mainly from osteoblasts has been demonstrated immunohistochemically in ossifying cartilage of cultured embryonic chick limb bones. The relevance of this observation to the mechanism of ossification is discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Current genetics 13 (1988), S. 235-239 
    ISSN: 1432-0983
    Schlagwort(e): Ribosomal protein ; Immunological homology ; Yeast ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Polyclonal antibodies raised against ribosomal protein (r-protein) L2 of Schizosaccharomyces pombe were used to check for cross-reaktions with total r-proteins of rat liver. Using this procedure, the rat liver r-proteins, L4 and L24, were identified as being immunologically related to yeast L2. In addtional, homologies between rat liver L4 and L24 were detected. The possible implications for the regulation of r-protein synthesis are discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    ISSN: 1432-1432
    Schlagwort(e): Carcinoembryonic antigen ; Evolution ; Gene family ; Human ; Rat ; Synonymous substitutions ; Silent molecular clock ; Evolutionary trees
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Various rodent and primate DNAs exhibit a stronger intra- than interspecies cross-hybridization with probes derived from the N-terminal domain exons of human and rat carcinoembryonic antigen (CEA)-like genes. Southern analyses also reveal that the human and rat CEA gene families are of similar complexity. We counted at least 10 different genes per human haploid genome. In the rat, approximately seven to nine different N-terminal domain exons that presumably represent different genes appear to be present. We were able to assign the corresponding genomic restriction endonuclease fragments to already isolated CEA gene family members of both human and rat. Highly similar subgroups, as found within the human CEA gene family, seem to be absent from the rat genome. Hybridization with an intron probe from the human nonspecific cross-reacting antigen (NCA) gene and analysis of DNA sequence data indicate the conservation of noncoding regions among CEA-like genes within primates, implicating that whole gene units may have been duplicated. With the help of a computer program and by calculating the rate of synonymous substitutions, evolutionary trees have been derived. From this, we propose that an independent parallel evolution, leading to different CEA gene families, must have taken place in, at least, the primate and rodent orders.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular evolution 24 (1987), S. 260-271 
    ISSN: 1432-1432
    Schlagwort(e): Mouse ; Rat ; Two-dimensional electrophoresis ; Quantitative variability of proteins ; Qualitative variability of proteins ; Protein classes ; Membrane proteins ; Organ-specific proteins ; Regulatory genes ; Speciation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Proteins of membranes and cytosols were extracted from the livers and brains of mice (inbred strain DBA/6J) and rats (inbred strain DA/Han) and separated by two-dimensional electrophoresis (2-DE). The 2-DE patterns were compared with regard to qualitative (spot position) and quantitative (spot intensity) characteristics of the proteins of these two species. The following results were obtained: (1) Brain had more (higher percentage) conservative proteins (proteins found in both mice and rats) than liver; (2) plasma membranes had more conservative proteins than the cytosols; (3) organ-unspecific proteins contained more conservative proteins than relatively organ-specific proteins; (4) the pattern of distribution of genetic variability among different classes of proteins represented by findings 1–3 was the same for the qualitative and quantative characteristics of the proteins; and (5) some observations indicated that quantitative variability occurred more frequently among proteins than did qualitative variability. Our conclusion is that regulatory sequences in the DNA (regulatory genes) are subjected to functional constraints that differ in strength among different classes of proteins by the same ratios as the constraints acting on the structural genes. The overall effect of the selective pressure is, however, less stringent for regulatory genes than for structural genes. The results obtained here by comparing two different species are very similar to previous results we obtained by studying different subspecies (inbred strains of the mouse). From this finding arises a new concept: the study of molecular evolution on the basis of different classes of proteins. Our results were compared with data from the literature that were obtained in part from studies on cultured cells. The comparison suggested that cultured cells have lost their tissue-specific proteins, and so generate predominantly extremely conservative proteins.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nutrition 26 (1987), S. 43-51 
    ISSN: 1436-6215
    Schlagwort(e): Dietary protein ; Vitamin A ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Es wurde der Einfluß von Qualität und Quantität von Nahrungsproteinen auf die Verteilung einer einzigen massiven Dosis von Vitamin A in verschiedenen Organen wachsender Wistar-Ratten untersucht. Die Untersuchungen wurden mit Casein- und Bengal-Gram-Diäten mit 20 % und 10 % Proteingehalt und auch mit radioaktiv markiertem Retinylacetat durchgeführt. Die Ergebnisse zeigen, daß die Leberspeicherung sowohl von Vitamin A aus der Nahrung als auch die einer einzigen starken Vitamin-A-Gabe (20 000 I.U.) stark herabgesetzt war bei Ratten, die nach der Bengal-Gram-Diät gefüttert wurden, verglichen mit Ratten, die auf Casein-Diät gesetzt waren. Im Gegensatz zur Leberspeicherung ist das Vitamin-A-Niveau im Plasma in allen Gruppen vergleichbar. Füttern niedriger Protein-Qualität reduzierte die Gewebeverteilung von [3H]-Retinylacetat sowohl bei Kontrollratten als auch bei solchen, denen eine massive Dosis Vitamin A gegeben wurde. Diese Untersuchung läßt vermuten, daß sowohl schlechte Qualität als auch unzureichende Mengen von Nahrungsproteinen nachteilige Einflüsse auf den Vitamin-A-Zustand wachsender Ratten haben.
    Notizen: Summary The influence of the quality and the quantity of dietary proteins on the distribution of a single massive dose of vitamin A in various organs of growing Wistar strain rats has been studied by using casein and bengal gram diets at 20 % and 10 % protein levels. The distribution of [3H]-retinyl acetate in various tissues was also investigated in these dietary conditions. The results show that the hepatic storage of dietary as well as a single massive dose (20,000 I.U.) of vitamin A was profoundly decreased in the rats fed on bengal gram diets as compared to those fed on casein diets. Regardless of hepatic stores, the plasma vitamin A levels were comparable in all the groups. Feeding of low quality of protein reduced the tissue distribution of [3H]-retinyl acetate in control as well as rats given a massive dose of vitamin A. This study suggests that both the poor quality and the inadequate quantity of dietary protein are detrimental influences on the vitamin A status of the growing rats.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nutrition 28 (1989), S. 130-141 
    ISSN: 1436-6215
    Schlagwort(e): bioavailability ; folic acid ; pharmaceutical preparation ; Bioverfügbarkeit ; Folsäure ; Arzneimittelzubereitung
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Untersuchungen zur Bioverfügbarkeit essentieller Mikronährstoffe (Vitamine, Mineralstoffe, Spurenelemente) aus Lebensmitteln wie auch aus Arzneimittelzubereitungen sind von entscheidender Bedeutung bei der Beurteilung des jeweiligen Beitrages zur Nährstoffversorgung bzw. zur Abschätzung eines möglichen Therapieerfolges. Die Durchführung derartiger Prüfungen erfolgt in der Praxis nicht selten nach unterschiedlichen Kriterien. Deshalb werden zunächst die Grundsätze erläutert, die bei entsprechenden Prüfungen für eine valide Bewertung von Nähr- bzw. Wirkstoffgemischen oder Monopräparaten bedeutsam sind. Abschließend wird die Ermittlung der Bioverfügbarkeit von Folsäure an einem Beispiel demonstriert. Zur Testung werden die postresorptiven Kurvenintegrale ermittelt, wobei die Daten auf das basale Ausgangsniveau bezogen werden. Zur Beurteilung der Bioverfügbarkeit findet neben dem maximalen Vitaminanstieg im Serum sowie der Zeit bis zum Konzentrationsmaximum insbesondere der Bioverfügbarkeitsquotient von Test- und Referenzzubereitung mit seinem 95%-VB Berücksichtigung. Die Ergebnisse zeigen, daß die exemplarisch eingesetzte Testsubstanz, 5-Formyl-Tetrahydrofolsäure, eine sehr gute Bioverfügbarkeit aufweist und daß unter Anwendung der beschriebenen Rahmenbedingungen eine objektive Bewertung der Bioverfügbarkeit möglich ist.
    Notizen: Summary Bioavailability studies of micronutrients (vitamins, minerals) from different food stuffs, as well as from pharmaceutical preparations are of great importance for the calculation of nutrient intake and/or the evaluation of the therapeutic value. In practice, bioavailability studies are not generally performed on a standardized level. For this reason basic criterions are presented and discussed. Finally, the investigation of the bioavailability of folate is demonstrated by an example. The parameters investigated are: the maximal concentration (cmax), the time to reach this maximum (tmax), and especially the bioavailability ratio determined from the area under the curve (AUC) after administration of the folic acid containing test and reference preparation. The results indicate that 5-formyl-tetrahydrofolic acid given in the tested form has nearly the same bioavailability (ratio: 1.02) as folic acid (pteroylmonoglutamic acid) in aqueous solution.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 14
    ISSN: 1432-041X
    Schlagwort(e): Vitellin ; Yolk granule ; Yolk protein ; Silkworm ; Embryogenesis ; Immunocytochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Vitellin was purified from eggs of the silkworm,Bombyx mori, by a new method in which vitellin was extracted from isolated yolk granules. The purified vitellin had a molecular weight of 540,000. An antibody against purified vitellin was prepared in rabbits. It reacted with the hemolymph vitellogenin as well as with purified vitellin, but not with other proteins in the hemolymph or in the extract from yolk granules. The anti-vitellin IgG was used to immunocytochemically locate vitellin in theBombyx non-diapause egg during early developmental stages. In the egg, just after oviposition, vitellin was located in internal yolk granules and in small yolk granules of the periplasm. During the early developmental stages studied, vitellin was not metabolized uniformly throughout the egg. The vitellin of the internal yolk granules located at the posterior-dorsal part and of the small peripheral yolk granules was utilized in 16 h and 2 days, respectively, after oviposition. A thin, very vitellin-poor layer was located between the periplasm and the vitellin-rich interior in the newly laid egg. it was always in close contact with the periphery where blastoderm and germ-band cells developed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    Development genes and evolution 194 (1985), S. 429-432 
    ISSN: 1432-041X
    Schlagwort(e): Tail bud ; Tail gut ; Gut ; Organogenesis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The formation of the tail portion of the primitive gut was investigated by light and electron microscopy in 10- and 11-day rat embryos. The observations permit the conclusion that the tail gut does not form as a posterior extension of the hindgut but originates from the tail bud mesenchyme by mechanism analogous to the secondary neurulation. It includes cell condensation, aquisition of apicobasal polarity and the radial, rosette-like arrangement around a central cavity. These cells bear the cytological characteristics of both the absorptive epithelial cells and the mesenchymal cells at their apical (adluminal) and abluminal ends respectively.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 16
    ISSN: 1420-9071
    Schlagwort(e): Rat ; cerebrospinal fluid, human ; analgesia ; naloxone ; pain indifference, congenital ; opiates, endogenous
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary CSF from a patient with congential indifference to pain was found to produce analgesia in the rat following intracerebroventricular injections. The analgesic effect was attenuated by pretreatment with naloxone suggesting the involvement of hyperactive endogenous opiate mechanisms in this patient.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 17
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1368-1369 
    ISSN: 1420-9071
    Schlagwort(e): Rat ; kidney ; hypertensive ; prostaglandin dehydrogenase ; hexokinase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary 15-Hydroxyprostaglandin dehydrogenase (PGDH) surged in hypertensive (SHR) and normotensive (WKY) rat kidney at 8 days of age, is greatest in SHR. Hexokinase fell in SHR at 17 days of age, but thereafter was similar to WKY. This suggests multisystem enzymatic abnormalities in SHR kidney during development of hypertension.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 18
    ISSN: 1420-9071
    Schlagwort(e): Rat ; alloxan diabetes ; intestinal villus ; alkaline phosphatase ; sucrase ; epithelial cells ; villus-crypt axis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The sucrase activity in enterocytes isolated from the villus crypt axis was found to increase in all regions of the villus from day 2 after induction of diabetes, and the increase continued until day 4. In contrast, alkaline phosphatase activity increased mainly in the apical one-third of the villus-crypt column, and the increase occurred abruptly on day 4 with increase in food intake.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 42 (1986), S. 169-171 
    ISSN: 1420-9071
    Schlagwort(e): Rat ; olfactory pathway selective lesions ; plasma corticosterone ; lactacidemia ; adrenal glands
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary In comparison to control rats, basal plasma corticosterone level and lactacidemia significantly increased in rats submitted to a bilateral lesion of the lateral olfactory tract and/or the anterior branch of the anterior commissure. Only the anterior branch of the anterior commissure induced hyperglycemia; that of the lateral olfactory tract exerted an opposite effect.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 20
    ISSN: 1432-041X
    Schlagwort(e): Major haemolymph proteins ; Development ; Cuticle ; Immunocytochemistry ; Ceratitis capitata
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The developmental profile of the major haemolymph proteins (ceratitins) inCeratitis capitata was studied. Ceratitin concentration in the haemolymph decreases dramatically during the last days of pupal life, while the amounts of ceratitins in whole organism extracts remain unchanged. By electrophoretic, immunological and immunofluorescence techniques it was revealed that ceratitins are reabsorbed by the fat body and a fraction of them is deposited in the cuticle. The possible role of ceratitins is discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 21
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1008-1010 
    ISSN: 1420-9071
    Schlagwort(e): Rat ; ethanol preference ; acetaldehyde self-administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Peripherally self-injected acetaldehyde in interaction with environmental and nutritional variables significantly enhances alcohol drinking in rats and suggests an involvement of acetaldehyde in voluntary alcohol intake.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 22
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 41 (1985), S. 1340-1342 
    ISSN: 1420-9071
    Schlagwort(e): Immunocytochemistry ; calmodulin ; secretory granules
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Calmodulin is a regulator of several calcium-dependent cellular processes. It has been suggested that it plays a role in the mechanism of secretion. Employing an indirect immunoperoxidase technique at the light microscope level, this study demonstrates the presence of calmodulin in several exocytotic cells (mast cells, thyroid follicular cells, neurohypophyseal neurosecretory terminals, pancreaticβ-cells and pancreatic acinus cells) in rat and man. The positive staining reaction for calmodulin was granular and at least in the case of rat mast cells it appeared to be associated with the granule membrane.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 41 (1985), S. 273-275 
    ISSN: 1420-9071
    Schlagwort(e): Rat ; embryo ; embryo ; rat ; β-hydroxybutyrate ; diabetes ; maternal ; fetal malformation ; malformation ; fetal ; ketone bodies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary In order to investigate further the relationship between maternal diabetes and fetal malformation, rat embryos were grown in vitro in the presence of β-hydroxybutyrate, one of the ketone bodies produced by diabetics. At 10 mM, β-hydroxybutyrate produced minor abnormalities and at 20 mM it produced major abnormalities in rat embryos.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 14 (1974), S. 283-289 
    ISSN: 1432-0827
    Schlagwort(e): Sodium fluoride ; Osteoporosis ; Bone ; Strength ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Beschreibung / Inhaltsverzeichnis: Résumé L'utilisation thérapeutique de fluorure de sodium a été recommandée dans le traitement de diverses maladies osseuses ostéopéniques. Cet emploi est basé principalement sur les effects ostéosclérotiques bien connus du fluorure de sodium, mais on connait mal son effet sur la force de résistance osseuse. L'influence de diverses concentrations de fluorure de sodium sur la force de résistance osseuse de jeunes rats soumis à des régimes riches et pauvres en calcium a été étudiée. L'administration de fluorure de sodium augmente le diamètre osseux, indiquant une stimulation de la formation de l'os périosté, mais la force de résistance osseuse est réduite ou non modifiée par l'ingestion de fluor.
    Kurzfassung: Zusammenfassung Die therapeutische Verwendung von Natriumfluorid ist für eine Anzahl von Knochenmangel-Krankheiten empfohlen worden. Die Empfehlungen basieren hauptsächlich auf den bekannten osteosklerotischen Wirkungen von Natriumfluorid; über dessen Effekt auf die Knochenstärke ist wenig bekannt. In dieser Arbeit wurde der Einfluß verschiedener Konzentrationen von Natriumfluorid auf die Knochenstärken von wachsenden Ratten mit hoher und niederer Calciumeinnahme untersucht. Die Verabreichung von Natriumfluorid erhöhte den Knochendurchmesser, was auf eine Stimulierung der Periostbildung hinwies, die Knochenstärke wurde jedoch durch Fluorideinnahme herabgesetzt oder nicht beeinflußt.
    Notizen: Abstract The therapeutic use of sodium fluoride has been recommended in a variety of osteopenic bone diseases. The recommendations are based mainly on the known osteosclerotic effects of sodium fluoride and little information is available as to its effect on bone strength. The influence of various concentrations of sodium fluoride on bone strength in growing rats on high and low calcium diets was studied. The administration of sodium fluoride increased bone diameter, indicating stimulation of periosteal bone formation, but bone strength was reduced or not affected by fluoride ingestion.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 25
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 13 (1973), S. 113-129 
    ISSN: 1432-0827
    Schlagwort(e): Kinetics ; Growth ; Epiphyses ; Hypophysectomy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Beschreibung / Inhaltsverzeichnis: Résumé La largeur de la métaphyse tibiale, la zone indifférenciée, la zone sériée et les cellules en dégénerescence ont été observées chez des rats Sprague-Dawley normaux et hypophysectomisés. La production cellulaire de la métaphyse est déterminée sur la base de la croissance osseuse longitudinale déterminée par l'oxytétracycline et la taille des cellules en dégénérescence. La diminution de la croissance osseuse longitudinale, en fonction de l'augmentation de l'âge et après hypophysectomie, est due partiellement, à la diminution de production cellulaire et partiellement à une décroissance de la taille des cellules en dégénérescence dans la métaphyse. L'influence de la production cellulaire et de l'activité mitotique prédomine.
    Kurzfassung: Zusammenfassung Die Breite der proximalen Wachstumsplatte der Tibia, deren undifferenzierter und säulenförmiger Zone und die Größe der nahe bei der Metaphyse auftretenden degenerativen Zellen wurden in normalen und hypophysektomierten Sprague-Dawley-Ratten bestimmt. Die Zellproduktion in der Wachstumsplatte wurde aus dem longitudinalen Knochenwachstum berechnet, welches mittels Oxytetracyclin und der Größe der degenerativen Zellen bestimmt wurde. Es wurde festgestellt, daß die Abnahme des longitudinalen Knochenwachstums bei zunehmendem Alter und nach Hypophysektomie zum Teil einem Rückgang in der Zellproduktion, zum Teil einer Verminderung der Größe der degenerativen Zellen in der Wachstumsplatte zuzuschreiben ist. Der Einfluß der Zellproduktion, und somit der mitotischen Aktivität, herrscht vor.
    Notizen: Abstract The width of the proximal growth plate of the tibia, its undifferentiated and columnar zone and the size of the degenerative cell close to the metaphysis, were determined in normal and hypophysectomized Sprague-Dawley rats. The cell production in the growth plate was calculated from the longitudinal bone growth determined with oxytetracycline and the degenerative cell size. It was found that the decrease in longitudinal bone growth with increasing age and after hypophysectomy, is due partly to a decrease in cell production, and partly to a decrease in degenerative cell size in the growth plate. The influence of cell production and thus the mitotic activity predominates.
    Materialart: Digitale Medien
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  • 26
    ISSN: 1432-0827
    Schlagwort(e): Rat ; Calvarium ; Electron microscopy ; Preosteoclasts ; Osteoclasts
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary This is a study of the fine structure of cells of the 20-day fetal rat calvarium. Special attention is given to identifying and characterizing preosteoclasts. These cells are relatively common and located largely, but not exclusively, at the endocranial bone surface. The preosteoclasts are characterized by abundant mitochondria, an incomplete perinuclear Golgi apparatus, and variable-shaped dense granules. The dense granules are unique in appearance in that they contain an internal dense matrix surrounded by a clear halo. Most granules are circular in shape but some are elongate or tubular in form. Granules with identical appearance are observed in osteoclasts. The preosteoclasts are mononucleate, or occasionally binucleate. It is suggested that because preosteoclasts are morphologically distinctive and relatively abundant, it should be feasible to separate these cells from a heterogeneous cell isolate.
    Materialart: Digitale Medien
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  • 27
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 34 (1982), S. 211-213 
    ISSN: 1432-0827
    Schlagwort(e): Rat ; incisor ; ameloblasts ; enamel ; 45Ca autoradiography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Rats were injected with45Ca and horseradish peroxidase to determine the patterns of45Ca incorporation into incisor enamel and the morphological types of the overlying maturation ameloblasts.45Ca autoradiography showed no differences in the patterns of incorporation into enamel between routinely embedded and freeze-dried specimens. Enamel overlaid by ruffle-ended ameloblasts was much more heavily labeled while that overlaid by smooth-ended ameloblasts showed only moderate labeling. The observations lend further support to the hypothesis that the ruffle-ended cells are very active in mineralizing enamel and that the smooth-ended cells are in a passive, restorative phase.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 33 (1981), S. 177-180 
    ISSN: 1432-0827
    Schlagwort(e): Connective Tissue ; Vitamin D deficiency ; Hydroxyproline excretion ; Glycosaminoglycan excretion ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The urinary excretion of two connective tissue metabolites was studied in both control and vitamin D deficient rats. Hydroxyproline (HyPRO) excretion was determined after 2, 13 and 22 months (experiment I). It decreased with aging in animals receiving the control diet. On the contrary, this excretion increased as a function of age in vitamin D deficient animals. At the age of 22 months, HyPRO excretion was respectively 31 and 1708 µg a day in control and deficient animals. HyPRO and glycosaminoglycans (GAG) excretion was measured on a group of both control and vitamin D deficient rats at the age of 21 months (experiment II). These results confirm the high excretion of HyPRO in deficient animals. On the contrary, the GAG excretion was higher in control animals than in deficient ones, the mean excretion being respectively 412 and 234 µg a day.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 32 (1980), S. 63-68 
    ISSN: 1432-0827
    Schlagwort(e): Rat ; Bone formation ; Fluorochrome ; Microphotometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary A method for quantitative studies of the formation rate of bone has been developed. After vital staining with calcein, the fluorescence of a bone section was measured with a microphotometer controlled by a mini computer. After staining the bone structure with alizarin red S in a second step, the section was measured in transmitted light. The two data sets were combined and the shortest distances between the bone surface and the fluorescence lines were computed. With this information the distance distribution and the bone area between the label and the surface could be calculated in two different ways: with the single labeling and the continuous labeling techniques. The advantages and disadvantages of the two methods are discussed and compared with those of other techniques.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 32 (1980), S. 113-122 
    ISSN: 1432-0827
    Schlagwort(e): Rat ; Bone ; Metaphysis ; Quantitative ; Aging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The purpose of this work was to analyze the proximal tibial metaphysis of the 170 g rat in a quantitative histologic fashion which would allow some relation to tissue age to be established. Stained 3 µm thick tissue sections were analyzed with the aid of a Merz grid on an eyepiece reticule and a light microscope. Tissue mass and cell distribution were studied in all areas. The rate of change in tissue mass during aging of the metaphysis was calculated. Two regions of the metaphysis were identified. One, corresponding to the primary spongiosa, less than 4.45 days of age, is a region of high turnover of hard tissue and high numbers of osteoblasts and osteoprogenitor cells. The other, corresponding to the secondary spongiosa, is a region of relatively low net tissue turnover and low numbers of osteoblasts and osteoprogenitor cells. Osteoclasts were found relatively more uniformly distributed through the metaphysis than were osteoblasts and osteoprogenitor cells. The rate of bone formation in the primary spongiosa is 50 times that found in the Haversian bone of the rib of 5-year-old humans and about 500 times that found at the cortical-endosteal surface of ribs of 5-year-old humans. It is argued that both cell distribution and tissue distribution in the metaphysis support the concept that osteoblasts and osteoclasts, rather than osteocytes, are responsible for the maturation of the metaphysis. The inhomogeneous distribution of both cells and tissue in the metaphysis has definite meaning for the interpretation of findings concerning the incorporation of radionuclides into the skeleton.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 31
    ISSN: 1432-0827
    Schlagwort(e): Rat ; Hypophysectomy ; Dietary phosphorus deprivation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The demands of growth are known to exacerbate the effect of phosphorus deprivation (PD). We examined whether changes associated with PD could be prevented in young rats in which growth and growth hormone (GH) were eliminated by hypophysectomy (HPX) and whether PD in normal intact rats (INT) was associated with increased secretion of GH. INT or thyroxine- and ACTH-replaced HPX rats were fed one of the three diets: 0.31% P (NP); 0.027% P (LP), and 0.31% P, pair-fed with LP-mates (NP-PF). The results indicate that HPX did not qualitatively alter several physiologic responses to PD: (a) serum and urinary phosphorus (P) decreased and urinary calcium (Ca) increased; (b) net intestinal Ca retention fell and duodenal sac uptake of45Ca rose; and (c) external P balance was restored and duodenal sac uptake of32P-phosphate increased. Only the hypercalcemia seen in INT, LP rats was prevented by HPX. In INT rats serum immunoassayable GH levels, measured in single samples, were not different between different dietary groups while pituitary bioassayable GH was reduced in both LP and NP-PF rats when compared to the NP rats. Thus, except for hypercalcemia, the physiologic responses associated with PD are not prevented by the elimination of growth and GH, and the development of these responses in INT rats was not associated with a consistent or specific alteration in GH secretion.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 32
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 33 (1981), S. 223-231 
    ISSN: 1432-0827
    Schlagwort(e): Protein deficiency ; Bone formation ; Skeletal development ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Protein deficiency was produced by freely feeding young rats a 1% lactalbumin diet for 12 weeks in order to study the effects of protein-calorie malnutrition on skeletal development. During the experiment the food and caloric intake and weight of the experimental animals decreased, while those parameters of the control animals progressively increased. However, when gross caloric intake was expressed as a function of the metabolic size of the animal, the caloric consumption was similar for both groups of animals. The protein-deficient animals exhibited micro-radiographic and histological features of an abnormal pattern of endochondral bone formation. Appositional bone growth, as determined by the daily appositional rate and the percentage of endosteal surfaces undergoing active bone formation, was significantly decreased in these animals, as was the percentage of periosteal surfaces exhibiting resorption. Both chemical analyses of the whole bone and electron probe microanalysis in the specific area of actively calcifying bone revealed no significant differences between the mineral content of control and protein-deficient animals. This study distinguishes the effects of protein deficiency from that of combined protein-calorie deprivation and demonstrates that the abnormal skeletal development observed was the result of a decrease in the quantity of bone formed rather than an altered mineral content.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 33
    ISSN: 1432-0827
    Schlagwort(e): Rat ; Incisor ; Amelogenesis ; Acid phosphatase ; Ferritin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Acid phosphatase was localized in rat incisor ameloblasts without prior decalcification. Whenβ-glycerophosphate was used as the substrate, an intense reaction was observed in the supranuclear region of the secretory ameloblasts. But the reaction was dramatically reduced at the transitional stage and was very weak in the maturation ameloblasts. Whenp-nitrophenylphosphate was the substrate, the reaction product was consistently seen in the Golgi cisternae and the vesicular components of the ameloblasts at all stages of enamel development. These observations suggest that there are two acid phosphatases in ameloblasts. One is in the secretory ameloblasts and the other in the transition and maturation ameloblasts. X-ray micro-analyses for Fe and Pb showed that Fe and acid phosphatase were in the ferritin-containing vesicles at the later stage of enamel maturation. This evidence suggests that ferritin is digested in these vesicles for the release of the Fe pigment to the enamel. An increase in the number of intercellular bridges between ameloblasts was correlated with the dramatic decrease in height of ameloblasts at the pigment release stage. The ameloblast membranes were acid phosphatase positive at the intercellular bridges whenp-nitrophenylphosphate was the substrate. This activity may be involved in the reduction in the surface area of the ameloblast membranes.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 34
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 34 (1982), S. 376-381 
    ISSN: 1432-0827
    Schlagwort(e): Matrix vesicles ; Bone ; Actin ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Preliminary indications of the occurrence of actin and myosin in crude matrix vesicle preparations have been reported previously. In the present study extracellular matrix vesicles from rat alveolar bone were isolated. They were further purified by a sucrose density gradient. SDS-polyacrylamide gel electrophoresis of the purified vesicles revealed the presence of a polypeptide with a molecular weight of 43 K daltons and with electrophoretic mobility identical to that of blood platelet actin. The limited proteolysis of both 43 K dalton vesicular polypeptide and actin byStaphylococcus aureus-V8-protease revealed three fragments with identical electrophoretic mobility. In addition, the vesicular preparations inhibited the activity of DNase I, a property typical of actin monomers. Filamentous material extracted from matrix vesicles showed ultrastructural features of F-actin. Reaction of this material with heavy meromyosin resulted in arrowhead formation, which is characteristic of acto-heavy meromyosin. The occurrence of actin in extracellular matrix vesicles may account for their budding from the osteoblastic plasma membrane, their possible motility in the matrix, and maintenance of the spherical shape.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 35 (1983), S. 107-110 
    ISSN: 1432-0827
    Schlagwort(e): Calcium ; Glucocorticoid ; Vitamin D ; Osteoporosis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Eighty-eight adult male Sprague-Dawley rats were given a diet with either (a) 0.5% Ca and 0.6% P or (b) 0.01% Ca and 0.6% P. Osteopenia was created by adding prednisolone to the diet. The prophylactic effect of oral 1,25(OH)2D3 on the osteopenia was studied. It was found that prednisolone osteopenia in the rat was associated with defective Ca absorption. By giving an oral dose of 1,25(OH)2D3, it was possible to maintain normal Ca absorption during prednisolone treatment and to prevent the bone loss. No significant hypercalcemia or any kidney calcifications were seen. These results are in contrast to earlier findings, in which subcutaneous administration of 1,25(OH)2D3 failed to prevent prednisolone osteopenia because of its tendency to increase bone resorption.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    International journal of biometeorology 32 (1988), S. 17-20 
    ISSN: 1432-1254
    Schlagwort(e): Epilepsy ; Electromagnetic fields ; Rat ; Audiogenic seizure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Geographie , Physik
    Notizen: Abstract In order to study the possible association between epileptic seizures and natural electromagnetic fields, 32 female audiogenic seizure (AGS)-susceptible rats were exposed to simulated 10 kHz and 28 kHz atmospherics and to a sinusoidally oscillating magnetic field with a frequency of 100 Hz and field strength of 1 A/m. After the electromagnetic exposure, seizures were induced in the rats with a sound stimulus. The severity of the seizure was determined on an ordinal scale, the audiogenic response score (ARS). The time from the beginning of the sound stimulus to the onset of the seizure (seizure latency) and the duration of the convulsion was measured. No differences from the control experiments were found in the experiments with simulated atmospherics, but the 100 Hz magnetic field increased the seizure latency by about 13% (P〈0.02). The results do not support the hypothesis that natural atmospheric electromagnetic signals could affect the onset of epileptic seizures, but they suggest that AGS-susceptible rats may be a useful model for studying the biological effects of electromagnetic fields.
    Materialart: Digitale Medien
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  • 37
    ISSN: 1432-1254
    Schlagwort(e): Atmospherics ; Carrageenan inflammation ; Rat ; Susceptibility ; Correlations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Geographie , Physik
    Notizen: Abstract Between the mean daily density of 28 kHz atmospherics and the onset of epileptic fits there is a highly significant correlation coefficient (r) of 0.30; there is a negative coefficient of −0.20 between the fits and the mean daily density of 10 kHz atmospherics. The onset of heart infarction is correlated with 28 kHz atmospherics (r=0.15). Furthermore, we have discovered that sudden deafness is also correlated with certain configurations of atmospherics. In this paper we report the following correlation coefficients between the inflammatory reaction of rats to a carrageenan injection (rci) into a hind paw and the mean daily pulse rate of atmospherics of the same day:r=0.49 for the 8 kHz atmospherics (P〈0.02) andr=0.44 for the 10 kHz atmospherics (P〈0.04). The correlations between rci reaction and other atmospherics (12 and 28 kHz) are smaller and not significant. By the method of multiple linear regression we found a multipleR=0.54 between rci reaction and the 8 and 10 kHz atmospherics (the regression function for the rci reaction is 0.15+0.004×8 kHz+0.002×10 kHz,P〈0.05).
    Materialart: Digitale Medien
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  • 38
    ISSN: 1432-2048
    Schlagwort(e): Immunocytochemistry ; Lectin (localization) ; Phaseolus (lectin) ; Phytohemagglutinin ; Seed (lectin)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract We have examined the properties and subcellular localization of phytohemagglutinin (PHA), the major lectin of the common bean (Phaseolus vulgaris.), in the axis cells of nearly mature and imbibed mature seeds. On a protein basis the axis contained about 15% as much PHA as the cotyledons. Localization of PHA was done with an indirect immunolabeling method (rabbit antibodies against PHA, followed by colloidal gold particles coated with goat antibodies against rabbit immunoglobulins) on ultra-thin cryosections which were embedded in plastic on the grids after the immunolabeling procedure. The embedding greatly improved the visualization of the subcellular structures. The small (4 nm) collodial gold particles, localized with the electron microscope, were found exclusively over small vacuoles or protein bodies in all the cell types examined (cortical parenchyma cells, vascular-bundle cells, epidermal cells). The matrix of these vacuoles-protein bodies appears considerably less dense than that of the protein bodies in the cotyledons, but the results confirm that in all parts of the embryo PHA is localized in similar structures.
    Materialart: Digitale Medien
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  • 39
    ISSN: 1432-2048
    Schlagwort(e): Glycine (xanthine dehydrogenase) ; Immunocytochemistry ; Polyclonal antibody ; Root nodule ; Xanthine dehydrogenase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Xanthine dehydrogenase (XDH, EC 1.2.1.37) was purified from root nodules of soybean (Glycine max) and used to prepare a polyclonal rabbit antiserum. Monospecificity of this antiserum was ascertained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoprecipate. During root nodule development of soybean, only one form of XDH was detected on an immunological basis. Titration of XDH by immunoelectrophoresis showed that a remarkable increase in the amount of XDH occurred between two and four weeks after inoculation, in parallel with the increase in enzyme activity. Localization of XDH by immunofluorescence indicated that the enzyme was present exclusively in uninfected cells where it appeared to be associated with discrete organellels
    Materialart: Digitale Medien
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  • 40
    ISSN: 1432-2048
    Schlagwort(e): Cotyledons ; Endoplasmic reticulum ; Ferritin labeling ; Immunocytochemistry ; Phaseolus ; Protein (reserve) ; Reserve protein
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The ultrastructure of the storage parenchyma cells of the cotyledons of developing bean (Phaseolus vulgaris L.) seeds was examined in ultrathin frozen sections of specimens fixed in a mixture of glutaraldehyde, formaldehyde and acrolein, infused with 1 M sucrose, and sectioned at-80° C. Ultrastructural preservation was excellent and the various subcellular organelles could readily be identified in sections which had been stained with uranyl acetate and embedded in Carbowax and methylcellulose. The cells contained large protein bodies, numerous long endoplasmic reticulum cisternae, mitochondria, dictyosomes, and electron-dense vesicles ranging in size from 0.2 to 1.0 μm. Indirect immunolabelling using rabbit immunoglobulin G against purified phaseolin (7S reserve protein), and ferritin-conjugated goat immunoglobulin G against rabbit immunoglobulin G was used to localize phaseolin. With a concentration of 0.1 mg/ml of anti-phaseolin immunoglobin G, heavy labeling with ferritin particles was observed ober the protein bodies, the cisternae of the endoplasmic reticulum, and the vesicles. The same structures were lightly labeled when the concentration of the primary antigen was 0.02 mg/ml. Ferritin particles were also found over the Golgi bodies. The absence of ferritin particles from other organelles such as mitochondria and from areas of cytoplasm devoid of organelles indicated the specificity of the staining, especially at the lower concentration of anti-phaseolin immunoglobulin G.
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  • 41
    ISSN: 1432-2048
    Schlagwort(e): Immunocytochemistry ; (PEP carboxylase) ; PEP carboxylase ; Sorghum
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The localization of phosphoenol pyruvate carboxylase (EC 4.1.1.3.1.) in the leaf cells of Sorghum vulgare was investigated by using three techniques: the conventional aqueous and non aqueous methods gave conflicting results; the immunocytochemical techniques clearly showed that the enzyme is predominantly located in the cytoplasm of mesophyll cells.
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  • 42
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 631-634 
    ISSN: 1432-1041
    Schlagwort(e): salbutamol ; albuterol ; pharmacokinetics ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Salbutamol was administered to sixteen healthy male volunteers intravenously and by mouth in liquid, tablet, and capsule form using a Latin-Squares design. Pharmacokinetic parameters from intravenous data were similar to previously reported values obtained with oral administration, with a mean terminal half-life of 3.8 h and a mean clearance of 439 ml·min−1·1.73 m−2. Peak plasma concentrations of 10–20 ng·ml−1 were obtained 1–3 h following oral administration. The absolute bioavailability of each of the oral preparations was 44%. While statistically significant differences in lag time and time to peak concentration were noted among the various oral preparations, the drug is rapidly absorbed in all three dosage forms and the observed differences are unlikely to be of clinical significance.
    Materialart: Digitale Medien
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  • 43
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 7 (1974), S. 269-273 
    ISSN: 1432-1041
    Schlagwort(e): Digoxin ; particle size ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Measurement was made of digoxin particle size in three brands of digoxin powder used for tablet manufacture. The geometric mean particle diameters were 20, 22 and 29 µm. When the 22 µm powder was administered within a cachet absorption of the digoxin occurred slowly and low steady state levels were obtained. Ball milling of the 22 µm powder was used to produce powders of mean diameters 12 and 3.7 µm. These powders produced more rapid and more complete absorption of the digoxin. The results indicate that particle size is a major factor in the biological availability of digoxin formulations.
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 6 (1973), S. 22-25 
    ISSN: 1432-1041
    Schlagwort(e): Naproxen ; suppository ; bioavailability ; tissue response ; anti-inflammatory ; analgetic
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absorption of naproxen from Witepsol and Carbowax suppository bases was found to compare closely to that from an equivalent oral dose. Although the drug was readily absorbed from both rectal formulations, naproxen in Witepsol base produced a more rapid rise of plasma levels. — No significant local tissue irritation occurred following a course of six suppositories as determined by anoscopy and rectal biopsy. — No objective or subjective side effects were noted.
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 34 (1988), S. 77-82 
    ISSN: 1432-1041
    Schlagwort(e): N-acetylcysteine ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and bioavailability of N-acetylcysteine (NAC) have been determined after its intravenous and oral administration to 6 healthy volunteers. According to a randomized cross-over design each subject received NAC 200 mg i.v. and 400 mg p.o., and blood samples were collected for 30 h. Reduced NAC had a volume of distribution (VSS) of 0.59 l·kg−1 and a plasma clearance of 0.84 l·h−1·kg−1. The terminal half-life after intravenous administration was 1.95 h. The oral bioavailability was 4.0%. Based on total NAC concentration, its volume of distribution (VSS) was 0.47 l·kg−1 and its plasma clearance was 0.11 l·h−1·kg−1. The terminal half-life was 5.58 h after intravenous administration and 6.25 h after oral administration. Oral bioavailability of total NAC was 9.1%.
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 34 (1988), S. 315-317 
    ISSN: 1432-1041
    Schlagwort(e): albendazole ; echinococcosis ; bioavailability ; food intake ; fatty meal
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the systemic availability of oral albendazole in 6 patients with echinococcosis either fasting or with breakfast. Albendazole sulphoxide, the pharmacologically active principle, was assayed by HPLC. Mean plasma concentrations and AUCs were 4.5 times higher when albendazole was given with breakfast than when administered in the fasting state. We conclude that therapy of echinococcosis with albendazole requires the drug to be taken with meals and that administration on an empty stomach might be more appropriate when intraluminal effects are desired, e.g. for intestinal parasites.
    Materialart: Digitale Medien
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 34 (1988), S. 469-473 
    ISSN: 1432-1041
    Schlagwort(e): xamoterol ; cardiac failure ; beta1-adrenoceptor partial agonist ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of xamoterol, a β-adrenoceptor partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 12 healthy male subjects. They received 14 mg i.v. and oral doses of 50 and 200 mg as a tablet and 200 mg as a solution in a 4 way cross-over design. After i.v. dosing the elimination half-life was 7.7 h, the total body clearance was 224 ml·min−1 and the volume of distribution at steady-state (Vss) was 48 l. Sixty-two percent of the dose was recovered unchanged in urine. After oral doses, the absolute bioavailability of xamoterol was shown to be 5% irrespective of whether the dose was administered as a tablet or solution. Peak plasma concentrations occurred at about 2 h for the tablet dose and slightly earlier (1.4 h) for the solution. Peak plasma concentration, AUC and urinary recovery of unchanged drug increased in proportion to dose. The apparent elimination half-life after oral doses (16 h) was significantly longer than that observed after an intravenous dose. Despite the low bioavailability, the degree of inter-subject variability of oral bioavailability was small probably indicating that the controlling factor is the hydrophilic nature of the molecule rather than extensive first pass metabolism or poor dissolution of xamoterol from the tablet formulation.
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  • 48
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 7 (1974), S. 81-86 
    ISSN: 1432-1041
    Schlagwort(e): Phenytoin ; single- and multiple dose pharmacokinetics ; dose-dependent kinetics ; bioavailability ; plasma concentration ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentration of phenytoin (diphenylhydantoin, DPH) have been studied in 5 volunteers after single oral and iv doses (5.0 mg sodium DPH/kg), and after multiple oral doses (2.0 mg sodium DPH/kg b.i.d. for 12 days). The data were analysed according to a one compartment model. The plasma half-life was 14.5 h±1.2 S.D. after i.v. administration, its apparent volume of distribution varied little (0.52 l/kg±0.04) and its bioavailability ranged between 0.70 and 1.0 (mean 0.87). After oral administration peak plasma concentrations were reached in 4 to 12 h. Elimination curves were slightly convex, probably due to an effect of slow absorption. Steady-state plasma levels varied twofold between individuals after multiple oral doses and exceeded those predicted from the single i.v. dose by 29 to 77%. The discrepancy was considered to be due to transition to dose-dependent kinetics.
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 625-629 
    ISSN: 1432-1041
    Schlagwort(e): disopyramide ; bioavailability ; saturable binding ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of disopyramide were determined in 10 healthy volunteers after a 300 mg oral dose and again after a 2mg/kg i.v. dose. The unbound clearance was 599 ml/min and the unbound renal clearance 310 ml/min. The terminal elimination rate constant of unbound drug was 0.180 h−1 after the i.v. dose and 0.203 h−1 after the oral dose. The absorption rate constant was 0.53−1 and the maximum peak concentration occurred after 3.2 h. The bioavailability was 0.809 using the area under the unbound plasma concentration time curve. Although a saturable plasma protein binding was found in all subjects the bioavailability using the total concentration, in contrast to theoretical expectations, showed the same value (0.813) as the unbound concentrations.
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 34 (1988), S. 211-212 
    ISSN: 1432-1041
    Schlagwort(e): diclofenac ; sulglicotide ; bioavailability ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The bioavailability of diclofenac (D) was assessed in 12 healthy volunteers treated orally with single doses of 100 mg (retard formulation) and subsequently retreated with the same dose of (D) plus sulglicotide (S) 200 mg. (D) blood levels were measured by GLC in samples collected after 1, 2, 4, 6, 8, 12, 24 h. No relevant difference was seen in (D) bioavailability after (S) administration; after 8 h plasma levels of (D) were slightly higher after (S) (p〈0.05), but this difference can be considered incidental only. Thus, sulglicotide does not interfere with the bioavailability of diclofenac, and can be administered concurrently with the latter to prevent possible gastric injury by the antiinflammatory drug.
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 21-24 
    ISSN: 1432-1041
    Schlagwort(e): doxazosin ; hypertension ; alpha-adrenergic blockade ; bioavailability ; pharmacokinetics ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mm Hg in the supine and 13/18 mm Hg in the standing position. Adverse effects were generally mild and of brief duration.
    Materialart: Digitale Medien
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 69-75 
    ISSN: 1432-1041
    Schlagwort(e): L-carnitine ; pharmacokinetics ; intravenous and oral doses ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 and 6 g was studied in 6 healthy subjects on a low-carnitine diet. Carnitine was more rapidly eliminated from plasma after the 6 g dose. Comparing the doses, the t1/2β of the elimination phase (β) was 6.5 h vs 3.9 h, the elimination constant 0.40 vs 0.50 h−1 and the plasma carnitine clearance was 5.4 vs 6.11 · h−1 for the 2 g and 6 g doses, respectively, showing dose-related elimination. Saturable kinetics were not found. The apparent volumes of distribution after the two doses were not significantly different and were of the same order as the total body water. Urinary recoveries of the 2 g and 6 g doses were 70% and 82%, respectively, during the first 24 h. Following the oral doses, there was no significant difference between the areas under the plasma carnitine concentration-time curves. Urinary recovery was 8% and 4% for the 2 g and 6 g doses during the first 24 h. Oral bioavailability was 16% for the 2 g dose and 5% for the 6 g dose. The results suggest that the mucosal absorption of carnitine was already saturated by the 2 g dose.
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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 89-91 
    ISSN: 1432-1041
    Schlagwort(e): flecainide acetate ; Wolff-Parkinson-White syndrome ; rectal absorption ; suppository ; micro enema ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The rectal absorption of flecainide from an aqueous solution, a fatty suppository and a polyethyleneglycol suppository was studied in one patient with supraventricular tachycardia (Wolff-Parkinson-White syndrome) refractory for oral anti-arrhythmic treatment. Rectal absorption was found to be fast (t1/2abs=1 h) and complete when flecainide was administered as a solution (relative bioavailability 100%). Flecainide was poorly absorbed from a fatty suppository. The polyethyleneglycol suppository gave absorption with a relative bioavailability of 80% and t1/2 abs=1.2 h.
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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 183-185 
    ISSN: 1432-1041
    Schlagwort(e): xamoterol ; cardiac failure ; beta1-adrenoceptor partial agonist ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of xamoterol, a β-adrenergic partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 8 cardiac failure patients (NYHA Class II) of mean age 62 years. After i.v. dosing, the elimination half-life was 7.4±0.4 h, the total body clearance was 228±30 ml·min−1 and the volume of distribution at steady-state was 56±91. 72.5±4.3% of the dose was recovered unchanged in urine. After the oral dose, the absolute bioavailability of xamoterol was shown to be 5.9%. Peak plasma concentrations occurred 1 to 2.5 h after the oral dose. The apparent elimination half-life was significantly longer after oral doses (16±2 h) compared to that observed after an intravenous dose. Renal clearance of xamoterol exceeded glomerular filtration rate as measured by creatinine clearance. The pharmacokinetics of xamoterol in cardiac failure patients with good renal function (creatinine clearance 〉90 ml·min−1) were similar to published data in young healthy male volunteers.
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  • 55
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 423-425 
    ISSN: 1432-1041
    Schlagwort(e): ketorolac tromethamine ; non-narcotic analgesic ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of ketorolac tromethamine, a potent non-narcotic analgesic agent used for relief of moderate to severe pain, has been studied in 15 healthy volunteers who received single 10 mg doses intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.) in a three-way cross-over design. The kinetics of i.v. ketorolac were characterized by a terminal half-life of 5.09 h, a small plasma clearance (CL = 0.35 ml·min−1·kg−1) and a small tissue distribution (Vss=0.111·kg−1, Vβ=0.17 l·kg−1; mean (SD). Following i.m. and p.o. administration, peak levels of approximately 0.8 µg/ml were rapidly attained (tmax = 0.8 and 0.9 h, respectively) and the systemic bioavailability was essentially complete.
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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 555-562 
    ISSN: 1432-1041
    Schlagwort(e): L-carnitine ; pharmacokinetics ; intravenous — oral doses ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 g and 6 g has been investigated in 6 healthy subjects on a low carnitine diet. Carnitine was more rapidly eliminated from plasma after the higher dose. Comparing the 2-g and 6-g doses, the t1/2β of the elimination phase (β) was 6.5 h vs 3.9 h, the elimination constant was 0.40 vs 0.50 h−1 and the plasma carnitine clearance was 5.4 vs 6.11 × h−1 (p〈0.025), thus showing dose-related elimination. Saturable kinetics was not found in the range of doses given. The apparent volumes of distribution after the two doses were not significantly different and they were of the same order as the total body water. Urinary recoveries after the 2-g and 6-g doses were 70% and 82% during the first 24 h, respectively. Following the two oral dosing, there was no significant difference in AUCs of plasma carnitine. Urinary recoveries were 8% and 4% for the 2-g and 6-g doses during the first 24 h. The oral bioavailability of the 2-g dose was 16% and of the 6 h dose 5%. The results suggest that the mucosal absorption of carnitine is already saturated at the 2-g dose.
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 385-389 
    ISSN: 1432-1041
    Schlagwort(e): oxazepam ; pharmacokinetics ; i.v.-/oral administration ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Six healthy volunteers received oxazepam 15 mg i.v. and orally at an interval of at least one week. The kinetic variables of i.v. oxazepam were: elimination half-life (t1/2β) 6.7 h, total clearance (CL) 1.07 ml·min−1·kg−1, volume of distribution (Vc) 0.27 l·kg−1 (0.21–0.49) and volume of distribution at steady-state (Vss) 0.59 l·kg−1. The intravenous disposition of unbound oxazepam was characterized by a clearance of 22.5ml·min−1·kg−1 and a distribution volume of 12.3 l·kg−1. After oral oxazepam the peak plasma level was reached in 1.7 to 2.8 h. The plasma t1/2β at 5.8 h was not significantly different from the i.v. value. Absorption was almost complete, with a bioavailability of 92.8%. Urinary recovery was 80.0 and 71.4% of the dose after intravenous and oral administration, respectively. Renal clearance (CLR) of the glucuronide metabolite was 1.10 ml·min−1·kg−1 (0.98–1.52). Oxazepam was extensively bound to plasma protein with a free fraction of 4.5%.
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  • 58
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1988), S. 643-645 
    ISSN: 1432-1041
    Schlagwort(e): ketoprofen ; food ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the pharmacokinetics of ketoprofen, a non-steroidal anti-inflammatory drug, in 12 patients after a single 100 mg oral dose both in fasting conditions and with a meal. Food significantly affected the peak plasma concentration of ketoprofen and decreased its absorption rate. However, the extent of absorption of ketoprofen, as reflected by the area under the plasma concentration time curve, appeared to be unchanged in the presence of food.
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  • 59
    ISSN: 1432-1041
    Schlagwort(e): cyclosporin ; pharmacokinetics ; infusions ; binding ; lipids ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary On the basis that unbound concentration better correlates with response than total plasma or blood concentration, the inter- and intra-subject variability in the distribution of cyclosporin within blood and to plasma components was studied in renal transplant patients. Pharmacokinetic aspects were also studied. Blood samples were analysed from patients who received the drug both by a 72-h i.v. infusion and orally (7 mg·kg−1 twice daily). Steady-state was reached within 18 h of starting the i.v. infusion; the plasma data were best fitted by a biexponential equation with half-times of 0.13–1.02 h and 4.3–13.9 h, associated with the two phases. The mean plasma clearance was 700 ml/min. Concentrations during the infusions measured by RIA and HPLC were comparable. Oral profiles showed rapid and extensive absorption. The peak plasma concentrations were 1460–1880 µg·l−1 and occurred 2–4 h after dosing, with bioavailability estimates of 41–113%. Concentrations measured by RIA were higher than by HPLC. Blood-to-plasma concentration ratio measurements of cyclosporin at 37°C decreased with increasing plasma concentration and increased with haematocrit. Fraction unbound, measured by ultracentrifugation, was in the range 0.042–0.122 with an average of 0.068, and varied little in some patients but showed systematic changes with time in others. Cyclosporin binding was found to be related not only to the triglyceride but, more particularly, to the cholesterol-related lipoproteins in plasma. Monitoring cholesterol may be helpful in identifying patients with extremes in binding or with widely varying binding.
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 29 (1986), S. 725-727 
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; meal effect ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary 10 healthy volunteers were given 40 mg furosemide p. o. with and without breakfast. The meal reduced the peak level of furosemide and decreased its bioavailability by approximately 30%. A heavy meal given to 5 of the subjects had no further effect. The reduced bioavailability caused a reduction in the diuretic effect.
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 37 (1989), S. 409-410 
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; metoclopramide ; antacids ; absorption ; bioavailability ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma cimetidine levels were determined in 9 normal subjects after a single oral dose of cimetidine 400 mg under control conditions, 2 h before metoclopramide 20 mg and 2 h after a potent antacid. The bioavailability of cimetidine was not significantly affected by metoclopramide and it was marginally reduced by the antacid.
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  • 62
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 37 (1989), S. 419-421 
    ISSN: 1432-1041
    Schlagwort(e): N-Acetylcysteine ; oral administration ; bioavailability ; healthy subjects ; suckable formulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and bioavailability of suckable tablets and granules of N-acetylcysteine (NAC) have been compared after oral administration of 400 mg doses to 10 healthy volunteers. The oral bioavailability of the NAC tablets was 103%. In a multiple dosing study of the same tablets in the same subjects, a high maintenance plasma level of NAC was revealed.
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 37 (1989), S. 423-426 
    ISSN: 1432-1041
    Schlagwort(e): prednisolone ; food intake ; enteric-coated tablets ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Prednisolone absorption and bioavailability of 10 mg enteric-coated (EC) and plain (uncoated) tablets were investigated after fasting and heavy meals (EC only) consumed to satiety in normal healthy volunteers. The same volunteers had also received 16 mg of prednisolone intravenously. In fasted subjects, the absolute bioavailability fraction, as normalised for intravenous doses, of prednisolone from plain tablets was 1.055 and from EC tablets was 0.996. The peak concentrations after plain and EC tablets were 309 and 249 ng/ml attained at 0.98 and 5.14 h, respectively. The means plasma elimination half-lives following the plain, EC tablets and intravenous administration in fasting conditions were 3.73, 3.89 and 3.78 h, respectively. Food interfered with both the absorption and the pharmacokinetics of prednisolone after EC tablets resulting in variability in its plasma levels. In some cases absorption of prednisolone was delayed for 12 h and remained at a measurable level for 24 h. In other cases, a normal absorption pattern was observed. This inter- and intrasubject variability of the effect of food appears to be related to its quantity, constituents and also the subjects physiological characteristics. It is concluded that enteric-coated prednisolone tablets should be administered at least 2 h between meals. However, for more predictable corticosteroid absorption (perhaps thus avoiding the therapeutic failure), plain prednisolone tablets are preferable.
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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    ISSN: 1432-1041
    Schlagwort(e): zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The systemic availability of a new antidepressant, zimelidine, and of its pharmacologically active metabolite, norzimelidine, was studied in six healthy male volunteers. Three single doses of zimelidine (25 mg and 100 mg orally and 25 mg i.v.) and two single doses of norzimelidine (25 mg orally and i. v.) were given to each volunteer allowing at least seven days between administrations. Plasma concentrations of zimelidine and norzimelidine were determined in serial blood samples by HPLC. Following oral zimelidine peak plasma concentrations of the metabolite were attained about 3 h after dosing. Oral administration of norzimelidine itself resulted in a plasma concentration profile for this compound that was similar to that observed after oral zimelidine. Utilising the plasma concentration data following intravenous infusion of each compound, the elimination half-lives for zimelidine and norzimelidine were calculated to be 5.1 h (range 4.3–6.0) and 15.5 h (range 10.6–22.9) respectively. The total body clearances of the 2 compounds were similar at 0.52 l · min−1 (range 0.26–0.70) for zimelidine and 0.56 l · min−1 (range 0.28–0.83) for norzimelidine. The substantially longer elimination half-life of norzimelidine was apparently the result of a larger volume of distribution (9.4 l · kg−1; range 7.8–11.4) for this metabolite, as compared to zimelidine (3.21 · kg−1; range 1.6–4.9). The calculated bioavailability of zimelidine was 26% (range 9.1–39) after the 25 mg oral dose, and 29% (range 14–46) after the 100 mg dose. The bioavailability of norzimelidine was 66% (range 36–91). However, oral administration of zimelidine resulted in as much or more norzimelidine reaching the systemic circulation, as the oral administration of norzimelidine itself. This is important as a large part of the activity of the drug may be due to the metabolite.
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  • 65
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 251-258 
    ISSN: 1432-1041
    Schlagwort(e): medigoxin ; digoxin ; dissolution rate ; proportionality ; bioavailability ; prediction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We compared our ability to predict the dose of medigoxin and of digoxin required to achieve a fixed serum concentration (the dose requirement) in 33 outpatients. Preliminary work supported the assumptions that the steady state glycoside concentration achieved was proportional to the daily dose given to an individual, and that the bioavailability of the different tablet presentations was similar for either glycoside. We were not able to predict the dose requirement from patient characteristics with any more certainty for medigoxin than for digoxin. Not only the between-patient variability in dose requirement, but also the within-patient variability, was similar for the two glycosides. However the digoxin used had a dissolution rate of over 90% in 1 h. When comparing medigoxin with digoxin of lower, or more variable dissolution rate, medigoxin may be preferable.
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 423-428 
    ISSN: 1432-1041
    Schlagwort(e): pyridostigmine ; myasthenia gravis ; pharmacokinetics ; bioavailability ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of pyridostigmine was evaluated after intravenous injection in two healthy male volunteers and after oral administration to five subjects. Plasma concentrations of pyridostigmine were determined after ion pair extraction from plasma and analysis by gas chromatography — mass spectrometry with chemical ionization, using d6-pyridostigmine as internal standard. Degradation of pyridostigmine in vitro was compensated for by use of the deuterated internal standard and by rapid cooling and separation of plasma after blood sampling. After intravenous administration of pyridostigmine 2.5 mg the plasma elimination half-life was 1.52 h, the volume of distribution was 1.43 l/kg and the plasma clearance 0.65 l/kg × h. The pharmacokinetic constants were very similar after oral administration of pyridostigmine 120 mg; the elimination half-life was 1.78±0.24 h, the volume of distribution 1.64±0.29 l/kg and the plasma clearance was 0.66±0.22 l/kg × h. The bioavailability was calculated to be 7.6±2.4%. When pyridostigmine was taken together with food, the time to reach the peak plasma concentration was prolonged from 1.7 to 3.2 h. Bioavailability, however, was not influenced by concomitant food intake. “Steady-state” plasma concentrations of pyridostigmine were measured in myasthenic patients on their ordinary dose schedule of cholinesterase inhibitor drugs. More than a seven-fold difference in steady-state plasma concentration was found between patients taking approximately the same daily dose of pyridostigmine.
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  • 67
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 343-350 
    ISSN: 1432-1041
    Schlagwort(e): orphenadrine ; single dose ; multiple doses ; bioavailability ; pharmacokinetics ; N-demethylorphenadrine ; metabolism ; dog ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentrations of orphenadrine were measured by a specific gaschromatographic method in 5 healthy male volunteers after a single oral dose of orphenadrine hydrochloride 100mg. The single dose pharmacokinetic profile of orphenadrine was evaluated from these data. The elimination half-life ranged from 13.2–20.1 h after the commercial tablet formulation. Plasma concentrations, determined in volunteers and patients under different conditions of repeated oral administration of the same formulation of orphenadrine hydrochloride exceeded the theoretical values, predicted from the single dose pharmacokinetics, by a factor 2 to 3. The elimination half-lives after discontinuation of treatment showed a 2 to 3-fold increase over the single dose values. This demonstrates a clear discrepancy between the multiple and single dose pharmacokinetics of orphenadrine. Experiments in dogs suggested competition for biotransformation between orphenadrine and its metabolite N-demethylorphenadrine. Product inhibition of this type could explain the observed discrepancy.
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  • 68
    ISSN: 1432-1041
    Schlagwort(e): indapamide ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Two formulations of indapamide tablets (2.5 mg) were given as a 5.0 mg dose and the subsequent blood levels were compared to those obtained after administration of a 5.0 mg solution. The study was conducted as a randomized three-way crossover design using healthy male volunteers. The drug was well tolerated by all the subjects involved. The area under the blood concentration versus time curve, extrapolated to infinity was essentially the same for all three formulations (4.2, 4.7, and 4.4 µg-h/ml). Statistical comparison of the blood levels from the two tablets showed that one tablet had a significantly greater maximum blood concentration (263 vs 231 ng/ml) and a significantly shorter time of maximum blood concentration (2.3 vs 3.5 h). Cmax (333 ng/ml) and tmax (0.7 h) values for the solution were significantly higher than either tablet. The average half-life (β-phase) for all three formulations was 15 h, while the average systemic clearance was 20 ml/min. Indapamide has a low clearance rate and there was no evidence that the drug undergoes a first-pass effect.
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 59-64 
    ISSN: 1432-1041
    Schlagwort(e): morphine ; rectal administration ; i.m. administration ; gas chromatographic mass spectrometric analysis ; bioavailability ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary 21 healthy women undergoing gynaecological operations received rectal premedication with morphine 0.3 mg/kg body weight. Plasma concentrations of morphine were followed for 4 h by a GC/MS technique. In most patients the peak plasma concentration was reached after 30 min; the mean peak plasma level of morphine was 18 ng/ml (range 8.5–57 ng/ml). The bioavailability of rectal morphine was determined in 6 patients, who received an i.m. injection of morphine at a second operation. The mean bioavailability of rectal morphine was 31% (range 12%–61%). None of the patients showed any clinical sign of respiratory depression, and there was no increase in end-tidal carbon dioxide tension measured in 5 patients operated under spinal block.
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  • 70
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 235-240 
    ISSN: 1432-1041
    Schlagwort(e): ergotamine ; pharmacokinetics ; migraine ; plasma drug levels ; i.v. administration ; i.m. administration ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of ergotamine has been investigated in migrainous patients using a new, specific, sensitive HPLC assay (detection limit 100 pg/ml plasma). 10 patients were given ergotamine tartrate 0.5 mg i.v. and 5 of them received the same dose i.m. 2–3 weeks later. Blood samples were collected for up to 54 h following administration and the plasma concentration were analysed. After intravenous administration the plasma ergotamine declined rapidly, with an initial distribution half-life of 3 min followed by a mean terminal half-life of 1.86 h (range 90–155 min). The mean total plasma clearance was 11.0 ml kg−1 min−1, and the volume of distribution (Vdβ ) was 1847.6 ml kg−1. Individual t1/2β showed a positive linear correlation with the individual Vdβ . The intramuscular absorption of ergotamine was rapid and maximum plasma levels were usually obtained 10 min following administration. The biological availability was incomplete and variable at 46.6% (range 28.3–60.8%).
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  • 71
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 127-136 
    ISSN: 1432-1041
    Schlagwort(e): statistical analysis ; nonparametric statistical methods ; bioavailability ; confidence interval ; ANOVA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary For a two-way cross-over design, which appears to be the most common experimental design in bioavailability studies, 95%-confidence limits for expected bioavailability can be obtained by classical analysis of variance (ANOVA). If symmetry of the confidence interval is desired about zero (differences) or unity (ratios) rather than about the corresponding point estimator, Westlake's modification can be used. Two nonparametric methods and their adaptations to bioavailability ratios are reviewed, one based on Wilcoxon's signed rank test (Tukey), and the other on Pitman's permutation test. The necessary assumptions and the merits of these procedures are discussed. The methods are illustrated by an example of a comparative bioavailability study. A FORTRAN program facilitating the procedures is available from the authors upon request.
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  • 72
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 791-796 
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; bioavailability ; diuretic effect ; urine sodium ; urine potassium ; power of ANOVA ; tablet formulations ; urinary flow rate ; normal volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The relative bioavailability and diuretic effect of 2 commercially available tablet preparations of furosemide 40 mg was examined in 10 healthy male volunteers. A close linear relationship between the urinary excretion rate of furosemide and the rate of sodium ion excretion in urine and/or flow rate of urine was demonstrated. There were no significant differences in the urinary excretion of furosemide, sodium and potassium ions or urinary volume following the oral doses. The difference in drug content affected the urinary recovery of furosemide over 24 h but had no effect on the pharmacological response. The analytical power of ANOVA using the various parameters of the responses to furosemide was no lower than when the parameters of urinary excretion of furosemide were used.
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  • 73
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 237-241 
    ISSN: 1432-1041
    Schlagwort(e): triamterene ; bioavailability ; pharmacokinetics ; metabolism ; hydroxy triamterene sulphate ; urinary excretion ; i.v. administration ; first-pass-effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. The formation of OH-TA-ester was very rapid and the concentration of the metabolite exceeded that of TA at all times. After i.v. administration the urinary recovery of TA and OH-TA-ester was 4.4% and 50.9%, respectively. The bioavailability of TA was 52%, corresponding to absorption of 83%. TA is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active.
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  • 74
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 449-453 
    ISSN: 1432-1041
    Schlagwort(e): canrenone ; pharmacokinetics ; plasma level ; bioavailability ; urinary excretion ; spironolactone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five healthy male volunteers received canrenoate-K 200 mg (Sincomen® pro injectione) by intravenous injection and one week later spironolactone 200 mg (Sincomen®-100) orally. Plasma levels and urinary excretion of unchanged canrenone were determined up to 24 h by a specific HPLC method. Following intravenous administration, the maximum plasma level of 2066±876 ng/ml was found after 29±15 min and thereafter the concentration declined with a half-life of 3.7±1.2 h. Total clearance was 4.2±1.7 ml/min·kg. After oral ingestion, the maximum concentration of 177±33 ng/ml was observed at 4.4±0.9 h. The absolute bioavailability of canrenone was 25±9%. Within 24 h, respectively 0.4 and 0.6 mg, canrenone were excreted by the kidney after intravenous and oral administration. The half-life of elimination was 4.9±1.8 h (i.v.) and 3.9±1.2 h (p.o.).
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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 513-520 
    ISSN: 1432-1041
    Schlagwort(e): xipamide ; electrolyte excretion ; bioavailability ; elimination ; extrarenal clearance ; chronic renal failure ; furosemide ; hydrochlorothiazide ; amiloride
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of a single oral dose of 40 mg xipamide on urinary excretion of Na+, K+, Cl−, Ca2+ and Mg2+ in healthy subjects and in patients with varying degrees of renal impairment was compared with various conventional diuretics. Xipamide caused marked excretion of Na+ and Cl−, whereas the diuretic produced only moderate kaliuresis; urinary excretion of Ca2+ was increased in proportion to Na+, like the loop diuretics. Xipamide affected electrolyte excretion even in patients with a creatinine clearance below 30 ml/min, as do the loop diuretics, too. Therefore, the pharmacodynamic characteristics of xipamide are more like those of a loop diuretic than of a thiazide. Xipamide was good bioavailable, its t1/2β was 7 h and urinary recovery of the undegraded drug was 40% of the given dose. In renal insufficiency, t1/2β increased from 7 to only 9 h, yielding a moderate increase in the AUC. Urinary recovery of the drug was reduced in proportion to the reduction in the creatinine clearance of the patient. Therefore, significant extrarenal elimination of the diuretic must be postulated, which suffices to prevent significant drug accumulation in renal failure.
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  • 76
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 105-110 
    ISSN: 1432-1041
    Schlagwort(e): phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
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  • 77
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 27 (1984), S. 595-602 
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; bioavailability ; generic tablet formulations ; intrasubject variability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Intrasubject variation in bioavailability (rate and extent) and disposition of furosemide 40 mg was investigated using a repeated, randomized, double-blind cross-over study in 8 healthy subjects. Two generic tablet formulations (Lasix and Furix) and intravenous furosemide were compared on 6 separate days. Extensive intrasubject variability after oral administration was observed in AUC, mean absorption time (MAT) and urinary excretion. The variability (error variance) within the dosage forms was as large as that between the two generics. These variations most probably depended on the absorption process, since the repeated i.v. doses showed only marginal intrasubject variability. Absolute bioavailability was 56% for Lasix and 55% for Furix (AUC). The range was 20 to 84% between individuals and the maximal range within one individual was 20 to 61%. Confidence interval and Bayesian analysis showed a high probability of non-equivalence not only between but also within the generics when the separate cross-over experiments were analyzed (8 observations). When extending the analysis to 16 observations, bioequivalence was demonstrated for the two generic tablets. Rate of absorption, quantified as MAT, was 128 min for Lasix and 98 min for Furix (16 observations). Since MAT was significantly longer (p〈0.001) than the mean residence time after the i.v. dose (57 min), absorption was evidently the rate-limiting step in the overall kinetics of oral furosemide. Intraindividual variation in absorption is a confounding factor in bioavailability studies of furosemide using limited numbers of subjects. This is important to consider when designing and evaluating bioavailability studies for drugs showing these variations.
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 29 (1985), S. 193-197 
    ISSN: 1432-1041
    Schlagwort(e): Glibenclamide ; intestinal absorption ; small and large intestine ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a study of eight volunteers and six patients, glibenclamide was placed at different sites of the gastro-intestinal tract under visual control. The dose was instilled once into the stomach and once into the duodenum of the eight volunteers in a randomized crossover design. The six patients underwent diagnostic colonoscopy, and the dose was placed into the ascending colon if pathological findings were not present. The area under the concentration-time curve, completed by extrapolation, and the mean residence time of the drug in the body were calculated. These pharmacokinetic characteristics were examined using a Jonckheere test for ordered alternatives and a Wilcoxon signed rank pair test. The means of the areas under the curve were 477±131 ng·h ml−1 for the stomach, 475±142 ng·h ml−1 for the duodenum and 486±301 ng·h ml−1 for the colon. The mean residence time changed from 2.67±0.35 h for the stomach to 2.42±0.48 h for the duodenum and 3.55±0.68 h for the colon. These results indicate that although glibenclamide is absorbed from all three sites of the gastro-intestinal tract to the same extent, the rates of absorption are different. It is discussed whether these findings really confirm the pH-partition hypothesis in drug absorption. Since glibenclamide — a weak acid — has a pK-value of about 6.5, these data seem to confirm the pH-partition hypothesis of drug absorption.
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  • 79
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 29 (1985), S. 251-253 
    ISSN: 1432-1041
    Schlagwort(e): paracetamol ; antacids ; acetaminophen ; bioavailability ; kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of two antacids on the bioavailability of paracetamol has been investigated in 12 young healthy volunteers. Following a random cross over design, each subject swallowed, on three separate occasions, one weak apart, 500 mg paracetamol alone, or together with two different aluminium hydroxide, magnesium hydroxide preparations (Dimalan and Maalox). Plasma paracetamol levels were measured by HPLC. The bioavailability of paracetamol was not altered by either antacid, but they both delayed the time to peak plasma concentration (0.85 h; 1.43 h; 1.25 h, without antacid, with Dimalan and with Maalox respectively). The peak plasma concentration was not affected by concurrent antacid administration.
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  • 80
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 30 (1986), S. 407-416 
    ISSN: 1432-1041
    Schlagwort(e): malotilate ; cirrhosis ; bioavailability ; liver fibrosis ; metabolite kinetics ; pharmacokinetics ; portal-systemic shunting ; urinary metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Malotilate, a sulphur-containing compound with antifibrotic and hepatoprotective properties in several animal models, has been investigated in cirrhotic patients. Nine patients with cirrhosis of various aetiologies and severity, and 4 healthy volunteers, participated in a pharmacokinetic study. After a single dose of 500 mg malotilate p.o. peak malotilate plasma concentration measured by GC-MS was 35 times higher in patients (median 0.70 µg/ml) than in controls (median 0.019 µg/ml). The median apparent oral clearance was approximately 50 times lower in cirrhotics (median 2.2l/min) than in healthy volunteers (118l/min). The apparent oral clearance was significantly correlated with indicators of portalsystemic shunting, such as the 2-h postprandial serum bile acids and the bioavailability of oral nitroglycerine. Urinary output of the glucuronidated metabolite-(M3), measured by HPLC, was normal in patients, whereas recovery of metabolite-M6 (resulting from ring opening and loss of sulphur) was reduced. Six patients in an open 6-month trial received malotilate 200 mg t.i.d. for 2 months and 400 mg t.i.d. for 4 months. The thrombocyte count increased and serum ferritin level fell in all patients, and serum cholinesterase rose and IgA decreased in 5 of 6. The other indicators of liver function did not show a significant change. Dry skin was the only possible adverse effect. It is concluded that first-pass elimination of malotilate is dramatically reduced in cirrhotics, and that a smaller amount of the drug reaches the liver in such patients. Malotilate was well tolerated, even in patients with advanced disease.
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  • 81
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 31 (1986), S. 177-182 
    ISSN: 1432-1041
    Schlagwort(e): glibenclamide ; bioavailability ; pharmacokinetics ; dissolution ; hypoglycaemia ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A study has been carried out investigating four different marketed oral preparations of glibenclamide, correlating the effectiveness of the drug in these preparations in lowering plasma glucose concentrations with (i) the in vitro dissolution of the drug, measured by the British Pharmacopoeal and Desaga methods, and (ii) the in vivo bioavailability, assessed in 12 healthy human volunteers. The two dissolution methods yielded different rank orders of ease of dissolution of the drug from the various preparations; the findings of neither dissolution method correlated adequately with the results of the in vivo bioavailability studies, which correctly predicted the abilities of the preparations to reduce plasma glucose concentrations. Relative to an oral glibenclamide solution the bioavailabilities of the drug from three tablet preparations were 0.69, 0.49 and 0.24. The mean elimination half-life of the drug was 1.5 h and assuming complete bioavailability of the drug from oral solution the mean systemic clearance was 0.095 l kg−1h−1, and the mean apparent volume of distribution was 0.20 l kg−1. It is concluded that it may be unsafe to use in vitro dissolution data as a basis for assessing the bioequivalences of different glibenclamide preparations intended for oral use.
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  • 82
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 415-418 
    ISSN: 1432-1041
    Schlagwort(e): diclofenac ; acetyl salicylic acid ; intravenous bolus administration ; oral administration ; interaction ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Previous studies have shown that aspirin interacts with orally administered diclofenac sodium, causing reduced peak concentrations, lower levels and decreased areas under curves. In this study, diclofenac sodium was administered orally and intravenously with and without aspirin, to 6 healthy female volunteers. After intravenous dosing both plasma levels and areas under curves were significantly reduced although none of the rate constants was affected. The volume of distribution of diclofenac was increased as was the plasma clearance. Oral administration with aspirin also resulted in lower plasma levels, particularly peak levels, and areas under curves. Comparison of AUC's for both modes of administration with and without aspirin suggested that lower levels after oral administration were not due to impaired absorption. These observations are best explained by decreased protein binding and increased biliary excretion of diclofenac in the presence of salicylate.
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  • 83
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 309-315 
    ISSN: 1432-1041
    Schlagwort(e): valproic acid ; sodium valproate ; suppositories ; micro-enemas ; steady-state concentration ; absorption ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Rectal and oral absorption of valproic acid and its sodium salt by man were compared to explore the possibility of rectal administration of the drug. The plasma concentration of valproic acid was measured by gas chromatography after a single oral dose of sodium valproate 600 mg, and after single rectal doses of sodium valproate 600 mg and valproic acid 520 mg, in a cross-over study in 7 volunteers. The rectal dosage forms included fatty suppositories and aqueous solutions. Compared with oral administration, rectal absorption of sodium valproate from an aqueous micro-enema was fast and complete. The free acid was absorbed more rapidly from fatty suppositories than was the sodium salt. The absorption rate from the rectum increased with the dose of valproic acid. Both findings are consistent with a diffusion — absorption mechanism based on the pH-partition hypothesis. Differences in the chemical composition of the fatty suppository base were not reflected in differences in absorption rate and relative bioavailability. No essential difference in absorption rate was observed if volunteers remained lying or sitting during the experiment. Rectal dosing with valproic acid 520 mg dissolved in 4 ml suppositories, twice a day resulted in steady-state plasma concentrations of 50 to 100 µg · ml−1, within the therapeutic range.
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  • 84
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 379-384 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; aminophylline ; obstructive lung disease ; microcrystalline ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1−1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.
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  • 85
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 53-55 
    ISSN: 1432-1041
    Schlagwort(e): digoxin ; bioavailability ; dose-dependency ; urinary excretion ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Nine healthy volunteers received single 0.25, 0.5, 1.0, 1.5, and 2.0 mg doses of oral digoxin tablets in random sequence on five occasions separated by at least 4 weeks. Urinary excretion of immunoassayable digoxin was determined from 8 consecutive 24 h urine samples collected after each dose. Mean values of cumulative urinary excretion of digoxin at the 5 doses were: 40.9, 35.6, 36.4, 34.1, and 33.5% of the dose (F=0.64; d. f.=4.32; N. S.). Mean values of urinary excretion half-life were: 2.48, 2.03, 2.20, 2.07, and 1.87 days (F=2.87; d. f.=4.32;p=0.05). Thus, the bioavailability of orally administered digoxin tablets in healthy volunteers is dose-independent over an 8-fold range of doses.
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  • 86
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 287-292 
    ISSN: 1432-1041
    Schlagwort(e): diacetolol ; acebutolol ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and bioavailability of diacetolol, the principal metabolite of acebutolol, were studied in 6 healthy subjects. Plasma concentrations were determined following a single intravenous injection of diacetolol 100 mg and three oral doses of diacetolol 100, 400 and 800 mg, in random order. The average oral bioavailability of diacetolol was F: 0.302±0.052 (100 mg), 0.363±0.052 (400 mg) and 0.426±0.068 (800 mg); the differences are not significant. The mean plasma half-life of the terminal phase, 7.94±0.26 h after intravenous administration, was significantly higher than after oral administration 12.27±1.00 h (100 mg), 12.82±1.59 h (400 mg) and 13.05±1.22 h (800 mg) (p〈0.02 to 0.05); the mean urine half-lives of the terminal phase were not significantly different. Renal clearance of diacetolol 10.2±0.81·h−1 represented about two-thirds of total body clearance 15.9±1.21·h−1. The results suggest either a first-pass effect or incomplete absorption of diacetolol after oral administration.
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  • 87
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 305-307 
    ISSN: 1432-1041
    Schlagwort(e): ketoprofen ; aluminium phosphate ; bioavailability ; antacid ; pharmacokinetics ; interaction study
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The purpose of this study was to determine whether a concomitant single dose of antacid (aluminium phosphate), or multiple doses of this antacid, administered prior to and with ketoprofen would alter the bioavailability of this non steroidal anti-inflammatory agent. The possible effects of aluminium phosphate were evaluated following administration of ketoprofen alone (Phase I), co-administration of antacid and ketoprofen (Phase II), and antacid for four days before administration of ketoprofen with co-administration on the day of the study (Phase III). There were no significant differences between treatment means for peak plasma concentration, time to peak plasma concentration, and area under the plasma concentration-time curve. The observed differences were due only to individual effects. The results indicate a lack of interaction between ketoprofen and the antacid aluminium phosphate (Phosphalugel)
    Materialart: Digitale Medien
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  • 88
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 359-365 
    ISSN: 1432-1041
    Schlagwort(e): tolfenamic acid ; anti-inflammatory agent ; human pharmacokinetics ; bioavailability ; intravenous administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent was studied in six healthy volunteers after an intravenous dose of 100 mg and oral doses of 100, 200, 400 and 800 mg. The disposition of intravenous tolfenamic acid could be described by two-compartment open model, with a central compartment volume (Vdc) of 5.6±0.31 (mean±SE), volume during β-phase (Vdβ) of 31±21, and a total elimination rate constant (k10) 1.6±0.1 h−1. The terminal elimination half-life was 2.5±0.6 h and the total plasma clearance 155±15 ml/min. The elimination occured principally by extrarenal mechanisms, the recovery of unchanged drug together with is glucuronide in urine averaging only 8.8% of the intravenous dose. The binding of tolfenamic acid to plasma proteins averaged 99.7%. The gastrointestinal absorption had a mean half-life of 1.7±0.1 h. Based on comparison of areas under the plasma concentration time-curves after intravenous and oral administration, the biovailability of tolfenamic acid capsules averaged 60%. The rate and extent of absorption and the rate of elimination of tolfenamic acid were independent of dose.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 89
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 293-301 
    ISSN: 1432-1041
    Schlagwort(e): metipranolol ; deacetyl metipranolol ; pharmacokinetics ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic parameters of deacetyl metipranolol were determined after i.v. infusion of increasing doses (6–25 mg) in 17 normal volunteers. In a second cross-over trial, deacetyl metipranolol 10 and 20 mg were infused in a further 10 subjects, and in a third trial another 20 volunteers received metipranolol 40 mg orally. Metipranolol is very rapidly and completely deacetylated in man, so all pharmacokinetic data refer to deacetyl metipranolol, which was assayed by gas chromatography-mass spectrometry. The pharmacokinetic analysis was performed using a recently developed model, using a volume of distribution which is variable with time. The following data were obtained after oral administration: (mean values); lag-time 7.3 min; tmax 50 min, invasion half-life 6.3 min; elimination half-life 3 h; urinary excretion of unchanged drug approximately 4% of the dose. The experiments with infusion of increasing doses, as well as the cross-over study with 10 and 20 mg i.v., showed dose-linearity of the kinetics. The respective mean half-lives of elimination were 2.6, 2.9 and 2.8 h. The mean total, renal and extra-renal clearances amounted to 1237 ml/min, 149 ml/min and 1068 ml/min, respectively. The distribution coefficient was 3.5 l/kg, and protein binding amounted to 70% within the range of therapeutic concentrations. Absolute bioavailability was found to be approximately 50% by several different evaluation procedures. Thus, the pharmacokinetic profile of metipranolol shares features of both the lipophilic and the hydrophilic groups of β-blocking agents.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 90
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 65-72 
    ISSN: 1432-1041
    Schlagwort(e): tranexamic acid ; pharmacokinetics ; bioavailability ; oral absorption ; influence of food ; plasma clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Tranexamic acid 1 g was given intravenously to three healthy volunteers. Plasma concentrations decayed in three monoexponential phases. Most elimination took place during the first eight hours, giving an apparent elimination half-life of approximately two hours. Plasma clearance ranged between 110–116 ml/min. The urinary recovery of tranexamic acid exceeded 95% of the dose. Ten healthy volunteers were given tranexamic acid 2 g orally on an empty stomach, and together with a meal. Food had no influence on the absorption of tranexamic acid, as judged by comparison of the peak plasma concentration, the time required to reach the peak, the AUC from zero to six hours, and the urinary excretion data. The oral bioavailability of tranexamic acid, calculated from 24 h urinary excretion after oral and intravenous administration, was 34% of the dose.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 91
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 171-173 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; neonates ; bioavailability ; food intake ; premature infants
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary 16 premature infants suffering from neonatal apnoea received orally an aqueous solution of theophylline 5 mg/kg bodyweight under fasting conditions and immediately before a milk feed. Bioavailability up to 7 h after administration was determined from the serum concentration-time course. The rate of absorption was significantly decreased if the drug was given with food; mean maximum serum concentrations were reached after 4.7 h instead of 1.6 h under fasting conditions. The area under the curve did not differ between the two patient groups which indicates that only the rate but not the amount of absorption was affected by food intake. The influence of feeding on the rate of absorption of theophylline by premature infants, which is more pronounced than in adults, can be related to particular functional factors in the gastrointestinal tract during the neonatal period.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 92
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 309-314 
    ISSN: 1432-1041
    Schlagwort(e): acetylsalicylic acid ; salicylic acid ; dipyridamol ; bioavailability ; kinetics ; rapid- and slow-release formulations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Acetylsalicylic acid (ASA) is a strong, irreversible inhibitor of platelet aggregation, but loses this activity following first-pass deacetylation to salicylic acid (SA). In order to compare the bioavailability of unchanged ASA from rapid- and slow-release formulations, the single-dose concentration profiles of ASA and SA were studied in healthy volunteers following intake of two different rapid-release (conventional and effervescent tablets) and three different slow-release (microencapsulated ASA in tablets and in capsules, and enteric-coated tablets) formulations of ASA, and of one slow-release formulation of sodium salicylate. Since anti-platelet therapy with ASA is often combined with dipyridamol, the influence of this drug was also examined. The concentrations of ASA and SA were measured by high-pressure liquid chromatography. While the bioavailability of SA from the 5 ASA formulations was essentially equal and similar to that of the salicylate formulation, the bioavailability and peak concentrations of ASA appeared to be the much greater after rapid-release than after slow-release formulations. Indeed, ASA was only rarely detected in systemic blood following intake of slow-release ASA. Co-administered dipyridamol did not significantly influence the kinetics of ASA or SA. It appears that rapid-release formulations of ASA should be prefered in anti-platelet therapy, either alone or in combination with dipyridamol.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 93
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 277-282 
    ISSN: 1432-1041
    Schlagwort(e): dexamethasone phosphate ; dexamethasone sulphate ; intravenous injection ; bioavailability ; pituitary-adreno-cortical suppression ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The metabolic fate and ACTH-supressant activity of two injectable dexamethasone esters, 21-phosphate and 21-sulphate, were studied in healthy men. After i.v. injection of 20 mg free steroid alcohol, dexamethasone phosphate was efficiently hydrolyzed to free dexamethasone, reaching its peak plasma concentration within 5 min. About 9% of the administered dose appeared in the urine as free dexamethasone. By contrast, virtually no free dexamethasone was found in plasma and urine after injection of dexamethasone sulphate. Pharmacokinetic analysis showed that dexamethasone sulphate had a shorter plasma half-life and a higher metabolic clearance rate than free dexamethasone. A larger fraction (60%) of dexamethasone sulphate was rapidly excreted unmetabolized in urine. The plasma cortisol level was significantly suppressed for more than 24 h after dexamethasone phosphate, while the plasma cortisol profile after dexamethasone sulphate merely showed physiological circadian variations. When the steroid esters were injected after pretreatment with metyrapone, a definite suppression of plasma ACTH was noted after dexamethasone phosphate, but again, dexamethasone sulphate was ineffective. These results cast serious doubt on the clinical value of dexamethasone sulphate as an injectable glucocorticoid, and critical reevaluation of this preparation is needed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 94
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 103-108 
    ISSN: 1432-1041
    Schlagwort(e): dexamethasone ; bioavailability ; pharmacokinetics ; ‘first-pass’ effect ; pre-systemic elimination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and oral biovailability of dexamethasone were studied in 6 patients with neurological disease being treated with high dosages of the drug. A specific high performance liquid chromatographic assay was used to measure dexamethasone concentrations. Unlike the previously published mean figure of 0.78 for the oral bioavailability of the drug given in single doses to healthy volunteers, the mean bioavailability of dexamethasone in the patients studied was 0.53±SD 0.40. It appeared more likely that this incomplete bioavailability was due to presystemic elimination than to poor absorption. The intravenous clearance of the drug was relatively high (0.4902±SD 2291 l kg−1, approximately 65% of expected hepatic plasma flow), the oral clearance higher (2.5804±SD 3.2181 l kg−1 h−1) while the absorption rate constant (4.8729±8.4998 h−1), suggested rapid absorption after oral administration. Prior phenytoin and possibly prior dexamethasone therapy is likely to have contributed to the higher clearance values of the drug in these patients than the values reported in healthy volunteers after single dose studies.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 95
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 465-471 
    ISSN: 1432-1041
    Schlagwort(e): metoclopramide ; pharmacokinetics ; bioavailability ; first-pass effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The time courses of plasma metoclopramide concentrations were followed in six subjects after oral and intravenous single dose administration. Plasma concentration-time data following i.v. administration in each subject were found to fit a two compartment model with a mean terminal half-life of 4.55 h±0.80 h and a mean distribution half-time of 0.35 h±0.09 h. Volumes of distribution were high (3.43±1.181 · kg−1), and clearances (0.53±0.191 · kg−1h−1) approached liver plasma flow. This suggests that metoclopramide occurs at higher concentrations in tissues than in plasma, and that its clearance is probably limited by liver blood flow rather than liver metabolic capacity. The post-absorption decline in metoclopramide plasma levels after oral administration was also biexponential in each subject. The terminal half-life was 5.17 h±0.98 h. Mean volume of distribution and mean clearance were similar to intravenous values (after adjustment for bioavailability). Oral absorption was rapid with peak plasma concentrations being reached at a mean time of 0.93 h. A mean bioavailability of 0.77 was calculated for the six subjects, and it was postulated that this incomplete availability is due to a first-pass effect. The inter-individual variation in the degree of ‘first-pass’ was considerable (0.47–1.14).
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 96
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 473-478 
    ISSN: 1432-1041
    Schlagwort(e): methadone ; bioavailability ; pharmacokinetics ; single dose ; stable isotope technique ; two compartment model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of methadone was studied in eight opiate dependent subjects during detoxification. Plasma concentrations were determined by mass fragmentography for 48 hours after administration of methadone 20 mg as tablets and simultaneous intravenous injection of deuterium-labelled methadone 20 mg. Pharmacokinetic parameters were calculated for the intravenous dose assuming a two compartment open model. Bioavailability was determined by comparing the areas under the plasma concentration versus time curves of unlabelled and labelled methadone. The beta-phase plasma half-lives varied five-fold, with a range from 8.5 to 47 h. The apparent volumes of distribution varied from 2.1 to 5.61/kg. Five patients had a bioavailability exceeding 90%, and three had lower bioavailabilities of between 41 and 76%. The unlabelled and labelled drug appeared to be pharmacokinetically equivalent. The data show that for a majority of these subjects the bioavailability was higher than 45%, the previously reported value. The marked individual variation in methadone pharmacodynamics and kinetics, and the possibilities both of cellular and methabolic tolerance, require an individually optimized dosage regimen.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 97
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 353-356 
    ISSN: 1432-1041
    Schlagwort(e): oxmetidine ; pharmacokinetics ; bioavailability ; plasma half-life ; clearance ; oral dose ; i.v. dose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentration curves and urinary excretion of oxmetidine after administration of single i.v. (100 mg) and oral (200 mg) doses have been studied in 11 patients with peptic ulcer disease. The mean bioavailability of the drug was 70% (range 53–91%). After intravenous administration, the mean plasmat 1/2β was 3.0 h, the mean apparent volume of distribution 0.7 l/kg, the mean total plasma clearance 12.3 l/h and the mean plasma renal clearance was 0.7 l/h. Following intravenous and oral administration an average of 6% and 3%, respectively, of unchanged drug was found in the urine. The plasma concentration curve after oral administration in most patients exhibited two maxima, with peak concentrations appearing between 45 and 210 min after dosing.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 98
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 85-90 
    ISSN: 1432-1041
    Schlagwort(e): lignocaine ; verapamil ; propranolol ; bioavailability ; predictions ; first pass effect ; oral clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary For drugs with a high hepatic clearance, bioavailability is low due to the so-called “first pass effect”. Prediction of the bioavailability for these drugs has been only lossely tested. It is proposed that by plotting the reciprocal of bioavailability versus the oral clearance, a straight line with intercept of unity and slope of reciprocal of hepatic blood flow should ensue. For lignocaine and verapamil, this relationship was found to be strong and gave good predictability, whereas for propranolol this relationship was weak and gave poor predictability. The proposed method may be of value in determining whether the low bioavailability of a drug is due to hepatic first pass metabolism.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 99
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 689-693 
    ISSN: 1432-1041
    Schlagwort(e): amiodarone ; bioavailability ; calculation ; linear pharmacokinetics ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Methods for estimating the bioavailability of drugs with long elimination half-lives are examined. Provided both absorption and disposition are linear a simple linear regression method is developed which can be used to calculate bioavailability in situations where only an incomplete estimate of the area under the curve (AUC) is available. The regression method and the traditional method of comparing the AUC following an oral dose to the AUC following an i.v. dose were applied to simulated data. It was found that the AUC ratio method works well as long as absorption is complete within the time over which the AUC is computed. The regression method is less precise than the AUC ratio method but is more accurate for drugs with long absorption half-lives. When applied to published data on a beta blocker the two methods produced comparable results. The bioavailability of amiodarone in three human subjects was calculated to be 0.20, 0.44 and 0.98 using the regression method with similar results from the ratio method. It is not possible to estimate the clearance of amiodarone from single dose data.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 100
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 405-407 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; drug absorption ; bioavailability ; food intake ; sustained-release preparations ; Theolin Retard
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absorption of theophylline from a sustained release tablet preparation (Theolin® Retard 300 mg) was studied in 10 subjects both when fasting and immediately after a standardized breakfast. Intravenous aminophylline was used as the reference material. Food did not influence the absorption from Theolin Retard. The bioavailability was complete (93% after 30 h) both with and without food, and no difference was found in the time to peak of the plasma concentration curve (7 h), or the mean residence time (14 h). The absorption characteristics, with predominantly zero order kinetics, did not change with concomitant intake of breakfast.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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