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  • pharmacokinetics  (93)
  • Rat  (85)
  • Lepidoptera  (48)
  • Inversion
  • Springer  (229)
  • 3
  • Wiley
  • 1985-1989  (229)
  • 1985  (229)
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  • 1985-1989  (229)
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  • 1
    Electronic Resource
    Electronic Resource
    Das Rückstandsverhalten von Chloramphenicol nach intramuskulärer Applikation beim Schwein (1985)
    Springer
    European journal of nutrition 24 (1985), S. 113-119 
    Details
    ISSN: 1436-6215
    Keywords: Chloramphenicol ; pharmacokinetics ; residue ; pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary Residues of Chloramphenicol (CAP) were examined in 24 pigs after intramuscular injection of 30 mg CAP/kg body weight. Two pigs were slaughtered after 3, 6, 12,18, 24, 36 hours, 2, 3, 6, 10, 21 and 30 days, respectively. CAP-concentrations were determined in muscle, blood, urine, liver, kidney, bile, and fat. Methods used were gas-liquid chromatography and radioimmunoassay. Detection limits reached were 1−5 ppb. The concentration-time curves obtained reflected a long elimination phase and allowed only calculation of this half-life. Elimination half-life was estimated to be for muscle, blood and urine 160–170 hours, for kidney 310 and for bile 250 hours. Significant correlations were found to exist between CAP-concentrations in plasma and muscle. It appears that blood would be a good body fluid for monitoring CAP-residues in tissue.
    Notes: Zusammenfassung Zur Untersuchung des Rückstandsverhaltens von Chloramphenicol (CAP) wurden 24 Mastschweine, 24–28 Wochen alt, intramuskulär mit 30 mg CAP/kg Körpergewicht behandelt und je 2 Tiere nach 3, 6, 12, 18, 24, 36 Stunden, 2, 3, 6, 10, 21 und 30 Tagen geschlachtet. Die CAP-Gehalte in Muskulatur, Blut, Urin, Leber, Niere, Galle und Fett wurden gaschromatographisch und radioimmunologisch bestimmt. Die Nachweisgrenze beider Methoden liegt in Abhängigkeit von der Matrix zwischen 1 und 5 ppb. Die erhaltenen Kinetiken weisen eine terminale Elimination auf, deren Halbwertszeiten für Muskulatur, Blut und Urin ca. 160–170 Stunden, für Niere 310 Stunden und für Galle 250 Stunden betragen. Die CAP-Konzentration in Muskulatur und Blut weisen eine signifikante, lineare Korrelation auf. Blutuntersuchungen könnten deshalb als Screening-Methode bei umfangreichen Rückstandskontrollen eingesetzt werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02020458
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  • 2
    Electronic Resource
    Electronic Resource
    Climbing by newly hatched larvae of the spotted stalk borer Chilo partellus to the top of sorghum plants (1985)
    Springer
    Entomologia experimentalis et applicata 39 (1985), S. 73-79 
    Details
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Pyralidae ; Chilo partellus ; Sorghum ; phototaxis ; climbing ; leaf anatomy ; surface wax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Une étude du comportement ascentionnel de chenilles néonates de Chilo partellus a montré que la phototaxie positive oriente l'insecte vers le sommet de la plante d'une façon plus importante que le site de ponte à la base du sorgho. La phototaxie est perdue après la pénétration dans le verticille, sous les effets combinés de l'odeur de l'hôte et de l'obscurité. Des insectes qui s'égarent sur les feuilles doivent retourner sur la tige pour parvenir à atteindre le verticille, et on a observé que les arêtes des feuilles, les épines orientées distalement et les cires de l'hôte provoquent ensemble une réorientation vers le bas de la feuille d'où l'ascension peut être poursuivie. II y a des différences suivant les cultivars en relation avec ces facteurs qui sont la cause partielle des différents niveaux de résistance à ce ravageur.
    Notes: Abstract A study of the mechanisms by which the newly hatched larvae of Chilo partellus reach the whorl from the oviposition site at the base of the plant is presented. A strong positive phototaxis is of primary importance. Reorientation is necessary, however, if larvae stray out onto leaves. Edge spines and leaf waxes are important in reorientation to the culm so that the climb can be continued. There are cultivar differences in relation to these factors which are a partial reason for different levels of resistance to this pest.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00338526
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  • 3
    Electronic Resource
    Electronic Resource
    Influence of hydrochlorothiazide on the pain threshold and on the antinociceptive activity of morphine, in rats (1985)
    Springer
    Cellular and molecular life sciences 41 (1985), S. 265-266 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; hydrochlorothiazide ; pain threshold ; antinociceptive activity ; analgesic activity ; morphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Hydrochlorothiazide, acutely injected in rats, has a weak analgesic activity per se and potentiates and prolongs the antinociceptive effect of morphine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02002628
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  • 4
    Electronic Resource
    Electronic Resource
    Systematics and evolution of holarctic Pierinae (Lepidoptera). An enzyme electrophoretic approach (1985)
    Springer
    Cellular and molecular life sciences 41 (1985), S. 24-29 
    Details
    ISSN: 1420-9071
    Keywords: Pieridae ; Lepidoptera ; systematics ; evolution ; enzyme electrophoresis ; genetic differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Enzyme electrophoretic data show a remarkably high degree of genetic similarity within the European group ofnapi s.l. whereas genetic differences exist at several loci between the European and the North American taxa ofnapi s.l. It is concluded that the European taxa did not differentiate to the species level and form a phylogenetically young group. The North American taxa included in this study are specifically distinct from Europeannapi and separated much earlier. Within these North American taxamarginalis, oleracea andvirginiensis did undergo speciation. The data show a splitting of the genusPieris into three species groups, each genetically differentiated to the same level. The splitting ofPieris into two genera, as suggested by earlier investigators, is not supported here.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02005856
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  • 5
    Electronic Resource
    Electronic Resource
    The alteration of calling behaviour by female Choristoneura fumiferana when exposed to synthetic sex pheromone (1985)
    Springer
    Entomologia experimentalis et applicata 37 (1985), S. 13-16 
    Details
    ISSN: 1570-7458
    Keywords: spruce budworm ; Choristoneura fumiferana ; Lepidoptera ; Tortricidae ; calling behavior ; sex pheromone ; bioassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Des expériences ont été menées au laboratoire pour examiner si la phéromone sexuelle synthétique de C. fumiferana pouvait altérer le comportement d'appel de femelles vierges de la même espèce. Un appareil a été conçu pour libérer alternativement — à des intervalles déterminés — un courant d'air portant de la phéromone sexuelle ou un courant d'air pur, dans plusieurs flacons contenant des femelles vierges. Le comportement sexuel de mouches de 0 et 2 jours a ainsi été observé. Indépendamment de l'exposition des femelles à la phéromone, il y avait deux pics quotidiens d'activité d'appel, l'un dans l'après-midi et l'autre après le crépuscule. Des papillons exposés au 1×10−6 mg ou 1×10−3 mg de phéromone avaient un premier pic d'appel au moins antérieur de 2 heures par rapport aux témoins. Ainsiily a vait un plus grand nombre de papillons engagés dans une activité d'appel en présence de la phéromone que chez les témoins.
    Notes: Abstract The calling behaviour of 0-day-old and 2-day-old virgin female eastern spruce budworm moths, Choristoneura fumiferana (Clem.) was observed during exposure to different concentrations of the synthetic female sex pheromone. Regardless of whether the females were exposed to pheromone or not, there were two daily peak periods of calling activity, one in the afternoon and the other after dusk. Those moths exposed to pheromone commenced calling at least 2 h earlier during their first peak of calling activity. Also, a greater number of moths engaged in calling when exposed to pheromone than those under control conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00366803
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  • 6
    Electronic Resource
    Electronic Resource
    Antifeedant and insecticidal properties of azadirachtin to the European Corn Borer, Ostrinia nubilalis (1985)
    Springer
    Entomologia experimentalis et applicata 38 (1985), S. 29-34 
    Details
    ISSN: 1570-7458
    Keywords: European corn borer ; Ostrinia nubilalis ; Pyralidae ; Lepidoptera ; azadirachtin ; antifeedant ; botanical insecticide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé On a examiné les propriétés anti-appétantes et insecticides de l'azadirachtine, une substance triterpénoïde provenant d'Azadirachta indica envers la pyrale du maïs Ostrinia nubilalis. La concentration effective pour causer 50% d'inhibition de l'alimentation larvaire (PC50) sur des disques foliaires a été de 3.5 ppm pour les larves de premier stade et de 24 μg/8 pour celle de troisième stade. L'azadirachtine a sévèrement réduit la croissance larvaire à des concentrations de 1 et 10 ppm dans une diète méridique et, éventuellement, a causé 100% de mortalité à 10 ppm et 90% à 1 ppm. A 0.1 ppm l'azadirachtine n'a pas eu d'effet significatif sur les larves maïs a modifié l'indice de masculinité en faveur des mâles au moment de l'émergence et a empêché l'oviposition chez les femelles. Les indices nutritionnels pour les larves naïves de troisième âge et celles ayant subi une accoutumance suggèrent que la réduction de croissance est le résultat d'une intoxication comme le démontre une efficacité réduite de transformation chez les groupes traités à l'azadirachtine, plutôt que des changements de digestibilité. Il n'y a pas d'évidence claire de tolérance dans le groupe ayant subi l'accoutumance. Les résultats suggèrent qu'à 10 ppm l'azadirachtine est un insecticide botanique efficace envers O. nubilalis.
    Notes: Abstract Azadirachtin, a triterpenoid substance from the neem tree, Azadirachta indica A. Juss., Meliaceae, was evaluated for its antifeedant and insecticidal properties to the European corn borer Ostrinia nubilalis Hübner. The 50% protective concentration for larval feeding on treated corn disks (PC50) was 3.5 ppm for neonate larvae and 24 ppm for third instar larvae. Azadirachtin severely reduced larval growth at 1 and 10 ppm in a meridic diet and eventually caused 100% mortality at 10 ppm and 90% at 1 ppm. At 0.1 ppm azadirachtin showed no significant effect on larvae but altered the sex ratio in favor of male moths during adult emergence and arrested oviposition of female moths. Nutritional indices for naive and habituated third instar larvae suggested that reduction of growth was due to toxicity as shown by a lowered efficiency of conversion in the azadirachtin treated groups, rather than changes in digestibility. No clear evidence of tolerance was observed in the habituated group. The data suggest that at 10 ppm azadirachtin is an effective botanical insecticide for control of O. nubilalis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00163349
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  • 7
    Electronic Resource
    Electronic Resource
    Response of females of the braconid parasitoid Microplitis demolitor to frass of larvae of the Noctoids, Heliothis zea and Trichoplusia ni and to 13-methylhentriacontane (1985)
    Springer
    Entomologia experimentalis et applicata 38 (1985), S. 109-112 
    Details
    ISSN: 1570-7458
    Keywords: kairomone ; frass ; Microplitis demolitor ; Heliothis zea ; Trichoplusia ni ; host selection ; behavior ; Hymenoptera ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Microplitis demolitor, un parasitoïde solitaire de plusieurs espèces de chenilles de noctuelles, a été introduit d'Australie aux Etats-Unis comme agent potentiel de contrôle biologique. Les fèces des chenilles d'Heliothis zea et Trichoplusia ni élevées sur des cotyledons de pois (Pink Eye Purple Hull Cowpea) stimulent les femelles à sélectionner un hôte, mais les fèces des chenilles des deux espèces élevées sur diète CSM ne possèdent pas cette activité. Un extrait hexanique des fèces des chenilles de H. zea élevées sur cotyledons de pois stimule également ce comportement, de même que le 13-methylhentriacontane, substance présente dans les fèces des chenilles de H. zea (Jones et al., 1971). Les femelles de M. demolitor exposées immédiatement avant leur lâcher en serre aux fèces des chenilles de H. zea, nourries de cotyledons de pois, parasitent un plus fort pourcentage (41.7%) de chenilles de H. zea que cells qui n'ont pas été exposées aux fèces (13.9%). Le comportement de sélection de l'hôte des femelles de M. demolitor est donc semblable à celui des femelles de Microplitis croceipes, un parasitoïde étroitement apparenté indigène des Etats-U-nis. La femelle, par exemple, est stimulée par une kairomone des fèces des larves de H. zea nourries sur des cotyledons de pois (incluant le 13-methyl-hentriacontane), la diète affecte l'activité kairomonale des fèces, et une exposition préalable aux fèces avant le lâcher stimule le comportement de sélection de l'hôte. La stimulation du comportement de sélection de l'hôte, au moment du lâcher peut être utilisée pour améliorer l'efficacité des lâchers des parasitoïdes dans les programmes de contrôle biologique.
    Notes: Abstract Microplitis demolitor Wilkinson, a solitary larval parasitoid of several species of Noctuidae, has been imported into the United States from Australia. A closely related species, Microplitis croceipes (Cresson), is native to the United States. The host-selection behavior of M. demolitor females is similar to that of M. croceipes in that it is stimulated by kairomones (including 13-methylhentriacontane) in the frass of Heliothis zea (Boddie) larvae, larval diet affects the kairomonal activity of the frass, and exposure to frass prior to release stimulates host-selection behavior. M. demolitor females also respond to frass from Trichoplusia ni (Hübner) larvae that had fed on Pink Eye Purple Hull Cowpea cotyledons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00361920
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  • 8
    Electronic Resource
    Electronic Resource
    The responses of some Lepidoptera to labiate herb and white clover extracts (1985)
    Springer
    Entomologia experimentalis et applicata 39 (1985), S. 177-182 
    Details
    ISSN: 1570-7458
    Keywords: biological control ; brassica ; labiate herbs ; larval feeding ; oviposition ; Lepidoptera ; Pieris brassicae ; Plutella xylostella
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Des plantes médicinales ont traditionnellement été utilisées en association avec des plantes cultivées dans l'espoir que leur odeur repousserait les insectes nuisibles. Des extraits à l'alcool et des essences volatiles de labiées médicinales ont été essayés au laboratoire pour examiner leur effets répulsif et dissuadant pour la ponte de Plutella xylostella et l'alimentation des chenilles de P. xylostella et Pieris brassicae. Les extraits alcooliques d'hysope, de romarin, de sauge, de thym et de trèfle blanc réduisent la ponte de P. xylostella sur des morceaux de feuilles de chou traitées. Les essences volatiles de sauge et de thym réduisent la ponte de P. xylostella sur des morceaux de feuilles de chou dans des expériences de choix. L'alimentation des chenilles de dernier stade de P. xylostella et P. brassicae dans des expériences de choix est réduite par l'application d'extraits alcooliques des labiées médicinales.
    Notes: Abstract Herbs have been traditionally used as intercrops with crop plants on the assumption that their odour repels pest species. Alcohol extracts and essential oils of labiate herbs were tested in the laboratory for deterrent/repellent responses to ovipositing Plutella xylostella (L.) and feeding larvae of P. xylostella and Pieris brassicae L. Alcohol extracts of hyssop, rosemary, sage, thyme and white clover reduce oviposition by P. xylostella on pieces of brassica leaf in dual-choice tests. Essential oils of sage and thyme reduce oviposition on pieces of brassica leaf. Feeding, in dual-choice tests, by final instar P. xylostella and P. brassicae larvae is reduced by application of alcohol extracts of herbs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00414506
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  • 9
    Electronic Resource
    Electronic Resource
    The influence of sex gland components on mating by the summerfruit tortrix moth, Adoxophyes orana, in the laboratory (1985)
    Springer
    Entomologia experimentalis et applicata 39 (1985), S. 233-239 
    Details
    ISSN: 1570-7458
    Keywords: Adoxophyes orana ; Lepidoptera ; Tortricidae ; strain ; sex pheromone ; sex gland components ; Z9-14:Ac ; Z11-14:Ac ; mating disruption ; spermatophores ; population density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Des essais ont été effectués en laboratoire en mettant des couples de papillons d'Adoxophyes orana F.v.R. pendant une semaine dans des boîtes d'élevage de 1,25 l avec ou sans composantes phéromonales. A la fin de l'essai, les femelles sont disséquées pour la recherche des spermatophores. L'inhibition des accouplements s'accroît avec l'augmentation de la charge des deux composantes principales de l'attractif, le Z9-14:Ac et le Z11-14:Ac (9:1) et elle décroît lorsque la densité de popultion passe de 1 à 5, 10, 20 couples de papillons par boîte. Chacune de ces deux composantes principales isolée provoque une réduction d'accouplements aussi importante que le mélange lui-même. Les composantes mineures Z9-12:Ac et 12:Ac ont pratiquement la même efficacité que les composantes principales, mais le 14:Ac et le Z11-14:OH sont sans effet. Des essais identiques effectués avec une souche d'A. orana récemment introduite en élevage continu, montrent qu'il suffit d'environ dix fois moins d'attractif pour provoquer le même effet que sur l'ancienne souche. Parallèlement à l'adaptation aux conditions d'élevage, le nombre de femelles non accouplées dans les témoins diminue progressivement et la fréquence des accouplements multiples augmente. II est donc vivement recommandé de travailler avec des souches continuellement renouvelées en élevage, ou avec les descendants directs d'individus prélevés en vergers. Les résultats obtenus sont commentés en relation avec la lutte par la technique de confusion.
    Notes: Abstract Couples of Adoxophyes orana F.v.R. were isolated for one week in small 1.25 l rearing boxes in the laboratory with sex gland components deposited on rubber caps. At the end of the trials females were dissected and spermatophores counted. Reduction of mating increased with the dose of a mixture of the attractant components Z9-14:Ac and Z11-14:Ac (9:1) but decreased with increasing density of 1 to 5, 10 and 20 couples per box. Each of the attractant components alone produced a mating inhibition equal to the mixture. The minor components Z9-12:Ac and 12:Ac had approximately the same effect as the main components, but 14:Ac and Z11-14:OH had no effect. Identical trials conducted on a strain of summerfruit moth newly introduced to our rearing showed that ten times less product was needed to achieve the same degree of mating inhibition as with the old strain. With adaptation to laboratory conditions the proportion of unmated females diminished and repeated matings occurred more frequently. In order to achieve meaningful results one must work with material from regularly renewed rearings, or better with the direct descendants of individuals from orchards. The results are discussed in relation to mating disruption of A. orana in orchards.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00217628
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  • 10
    Electronic Resource
    Electronic Resource
    Identification of components of the female sex pheromone of the potato tuber moth, Scrobipalpopsis solanivora (1985)
    Springer
    Entomologia experimentalis et applicata 38 (1985), S. 81-85 
    Details
    ISSN: 1570-7458
    Keywords: Scrobipalpopsis solanivora ; Lepidoptera ; Gelechiidae ; sex pheromone ; (E)-3-dodecenyl acetate ; (Z)-3-dodecenyl acetate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé S. solanivora est l'un des plus importants lépidoptères détruisant les pommes de terre en Amérique Centrale. L'analyse par chromatographie en phase gazeuse (GC) des produits obtenus par lavage de l'ovipositeur de femelles vierges, associée à des électro-anténnogrammes (EAG) a révélé un composé actif unique en EAG. Les durées de rétention pour ce constituant correspondaient à celles des acétates monoinsaturés à 12 carbones, et les analyses sur colonne GC liées avec une phase liquide cristal ont montré un pic principal correspondant à l'acétate (E)-3-dodécénul et un pic secondaire, correspondant à l'isomère Z, et au niveau de 2,5% du pic principal. L'acétate dodécyl a aussi été décelé en quantités variables, approximativement 10% du pic principal. Dans la nature, des pièges contenant de l'acétate (E)-3-dodécényl, seul ou mélangé avec 1 ou 2% de l'isomère Z, ont capturé autant des mâles de S. solanivora que des pièges contenant des femelles vierges, et certaines indications montrent que l'addition de 5% de l'isomère Z réduit les captures.
    Notes: Abstract The sex pheromone produced by virgin female S. solanivora moths has been shown to contain (E)-3-dodecenyl acetate with approximately 2% of the Z isomer by electroantennography and gas chromatography. In the field, traps baited with (E)-3-dodecenyl acetate alone or in combination with 1% or 2% of the Z isomer caught at least as many male S. solanivora moths as those baited with virgin female moths, and there was some evidence that addition of 5% of the Z isomer reduced catches.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00163356
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  • 11
    Electronic Resource
    Electronic Resource
    Influence of host plants on development, fecundity and egg hatchability of the arctiid moth Diacrisia casignetum (1985)
    Springer
    Entomologia experimentalis et applicata 37 (1985), S. 193-198 
    Details
    ISSN: 1570-7458
    Keywords: host plants ; larval feeding ; phenols ; proteins ; water contents ; nutritional quality ; fecundity ; egg hatchability ; Diacrisia casignetum ; Arctiidae ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé L'étude a porté sur l'évaluation de l'influence des feuilles de tournesol (Helianthus annuus) et de Mikana cordata sur le développement, la fécondité et l'éclosion des oeufs de D. casignetum Kollaz. La durée de développement et le gain de poids sur tournesol étaient plus importants que sur M. cordata. La durée de développement était statistiquement hétérogène (P〈0.05), ce qui peut être dû à des différences entre plantes. La fécondité et le taux d'éclosion chez les insectes élevés sur tournesol étaient plus élevés que ceux observés sur M. cordata, dont les résultats étaient aussi hétérogènes (P〈0.1 et〈0.05 respectivement). Les feuilles de M. cordata contenaient des taux relativement élevés de phénols et des rapports protéines sur phénols bas. Tout ceci suggère que les différences observées sont attribuables à des variations dans la qualité nutritive de ces hôtes et dans l'incorporation à la biomasse de l'insecte de matériaux phénologiques ingérés.
    Notes: Abstract Measurements were made of the differences between sunflower and climbing hempweed leaves for development, fecundity and egg hatchability of Diacrisia casignetum Kollar. Developmental time and weight gains of sunflower-fed larvae were respectively longer and greater than those of hempweed-fed ones. The development time and weight gain, attributable to differences in host plants, were statistically heterogeneous (P〈0.05-〈0.10). Relative fecundity and egg hatchability of sunflower reared insects were greater than those of hempweed reared ones, and these were also statistically heterogeneous (P〈0.1 and 〈0.05, respectively). Hempweed leaves contained relatively high titres of phenols and low ratios of proteins to phenols. Ovaries were heavier in insects reared on sunflower than on hempweed, whereas the level of phenols incorporated into the ovary was higher in insects fed on hempweed than those on sunflower. The differences in these parameters may be due to variations in nutritional quality of these hosts and incorporation of ingested phenolic materials to ovary and insect biomass.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00188210
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  • 12
    Electronic Resource
    Electronic Resource
    Constituents of host- and non-host plants deterring oviposition by the cabbage butterfly, Pieris rapae (1985)
    Springer
    Entomologia experimentalis et applicata 39 (1985), S. 21-26 
    Details
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Pieridae ; Pieris ; cabbage ; oviposition deterrents ; host selection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung Die Eiablage von Pieris rapae auf Kohl wurde gehemmt von einem Homogenisat aus Kohlblättern, das auf intakte Pflanzen gesprüht wurde. Ether-Extrakte der Kohlblätter wirkten im Gegensatz zu Wasserextrakten abschreckend. Ebenso zeigten Hexanextrakte anderer Wirtspflanzen eine hemmende Wirkung auf die Eiablage, während Wasserextrakte anderer Wirtspflanzen keine Wirkung aufwiesen. Dagegen aber verhinderten sowohl polare als auch unpolare Extrakte von Nicht-Wirtspflanzen die Eiablagen. Polare, abschreckende Substanzen in den Nicht-Wirtspflanzen Erysimum cheiranthoides und Capsella bursa-pastoris (Cruciferae) könnten Ursache dafür sein, dass P. rapae diese Pflanzen meidet. Chemische Substanzen mit sowohl abschreckender als auch stimulierender Wirkung spielen offensichtlich eine bedeutende Rolle für legebereite Schmetterlingsweibchen bei der Auswahl von Pflanzen als geeigneten Eiablageplatz.
    Notes: Abstract Oviposition by Pieris rapae L. on cabbage was deterred by homogenized cabbage tissue sprayed onto intact plants. Ether extracts of cabbage also were deterrent, but water extracts were not. Hexane extracts of other host plants deterred oviposition and water extracts had little or no effect. Polar as well as non-polar extracts of non-host plants inhibited oviposition. Polar deterrents in the non-host crucifers, Erysimum cheiranthoides and Capsella bursa-pastoris may explain the avoidance of these plants by P. rapae. Chemical deterrents, as well as stimulants, apparently play a major role in the acceptance or rejection of plants as hosts by ovipositing female butterflies.
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    URL: http://dx.doi.org/10.1007/BF00338520
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    Sex pheromone of the female currant borer, Synanthedon tipuliformis: Identification and field evaluation (1985)
    Springer
    Entomologia experimentalis et applicata 39 (1985), S. 131-133 
    Details
    ISSN: 1570-7458
    Keywords: (E,Z)-2,13-octadecadien-1-ol acetate ; (Z)-13-octadecen-1-ol acetate ; Synanthedon tipuliformis ; currant borer ; Lepidoptera ; Sesiidae ; sex pheromone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung (E,Z)-2,13-Octadecadienylacetat und (Z)-13-Octadecenylacetat wurden in Ovipositor-Extrakten des Johannisbeerglasflüglers Synanthedon tipuliformis kapillar-gaschromatographisch nachgewiesen. Die Strukturen wurden mittels Gaschromatographisch-Massenspektrometrie bestätigt. Das Verhältnis Dien/Monoen im Extrakt betrug 93:7. Mischungen der beiden Komponenten wie auch (E,Z)-2,13-Octadecadienylacetat allein lockten im Freiland Männchen dieser Glasflüglerart an.
    Notes: Abstract (E,Z)-2,13-octadecadien-1-ol acetate and (Z)-13-octadecen-1-ol acetate have been identified from the ovipositor extracts of the currant borer, Synanthedon tipuliformis (Clerck), by capillary GC, and the structures were verified by GC-MS. The diene/monoene ratio in the extract was found to be 93:7. Mixtures of these two compounds as well as the diene alone attracted conspecific males in the field.
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    URL: http://dx.doi.org/10.1007/BF00414499
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    Some applications of resultants to problems in computational geometry (1985)
    Springer
    The visual computer 1 (1985), S. 101-107 
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    ISSN: 1432-2315
    Keywords: Implicitization ; Inversion ; Intersection ; Resultant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract Resultants were originally developed in the 18th and 19th centuries to solve certain simple algebraic problems. Here we shall present some applications of resultants to several important problems in computational geometry, including the implicitization, inversion, and intersection of parametric rational polynomial curves and surfaces.
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    URL: http://dx.doi.org/10.1007/BF01898352
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    Tall gut formation in the rat embryo (1985)
    Springer
    Development genes and evolution 194 (1985), S. 429-432 
    Details
    ISSN: 1432-041X
    Keywords: Tail bud ; Tail gut ; Gut ; Organogenesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: 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.
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    URL: http://dx.doi.org/10.1007/BF00848557
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    Inversion of gravity and magnetic anomalies over some bodies of simple geometric shape (1985)
    Springer
    Pure and applied geophysics 123 (1985), S. 239-249 
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    ISSN: 1420-9136
    Keywords: Inversion ; Contact ; Thin sheet ; Interpretation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The general expression for gravity and magnetic anomalies over thin sheets and sloping contacts may be expressed as a polynomial of the formFx 2+C1Fx+C2F+C3x3+C4x2+C5x+C6. The initial parameters of the source are obtained from the coefficientsC 1, C2,..., C6 which may be solved by inverting a 6×6 matrix. The initial parameters are modified by successive iteration process using the difference formula until the root mean square error between the observed and calculated anomalies is a minimum. The regional background which may be in the form of a polynomial is estimated by the computer itself. This method is applied on a number of field anomalies and is found to yield reliable estimates of depth and other parameters of the source.
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    URL: http://dx.doi.org/10.1007/BF00877020
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    Inversion of arrival-times in a region of dilatancy anisotropy (1985)
    Springer
    Pure and applied geophysics 123 (1985), S. 375-387 
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    ISSN: 1420-9136
    Keywords: Inversion ; Dilatancy ; Anisotropy ; Local Earthquakes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract Shear-wave splitting has been identified in many three-component seismograms from two separate field experiments on a section of the North Anatolian Fault in North-West Turkey. These observations are consistent with shear-wave propagation through a zone of extensive-dilitancy anisotropy. A preliminary attempt has been made to confirm this interpretation by simultaneously inverting suites of arrival-times for hypocentral locations and for parameters describing an anisotropic halfspace. Although the inversion procedure is not globally convergent, it is possible to recognize the true solution by systematically varying the initial conditions. Applied to selected data sets, the inversion defines several anisotropic models that fit the data significantly better than a simple isotropic model, and display the anisotropy required by the shear-wave splitting. However, most of these anisotropic models are not superior when they are used to individually locate events in a much larger data set. However, for each experiment, there is a single model that produces clearly superior locations for the larger data sets than those of other anisotropic or simple isotropic models. Both models display similar velocity variations which are characteristic of propagation through distributions of biplanar cracks displaying orthorhombic symmetry. The principal axes of the two models are oriented in similar directions and are within 20° of the principal axis of regional stress derived from fault-plane solutions. The solutions indicate low velocities close to the tensional axis, as would be expected in extensive-dilatancy anisotropy.
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    URL: http://dx.doi.org/10.1007/BF00880737
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    Photoperiodically induced delayed insect metamorphosis: a larval oligopause inDiatraea saccharalis (1985)
    Springer
    Cellular and molecular life sciences 41 (1985), S. 267-269 
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    ISSN: 1420-9071
    Keywords: Diapause ; oligopause ; sugarcane borer ; Diatraea saccharalis ; Lepidoptera ; Pyralidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Sugarcane borers enter a state of delayed metamorphosis when exposed to a 12-h photophase at 21°C. Larval feeding, growth, and molting continues but pupation is suppressed under these conditions.
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    URL: http://dx.doi.org/10.1007/BF02002630
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    Changes in brush-border enzyme activities of intestinal epithelial cells isolated from the villus-crypt axis during the early phase of alloxan diabetes in rats (1985)
    Springer
    Cellular and molecular life sciences 41 (1985), S. 482-484 
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    ISSN: 1420-9071
    Keywords: Rat ; alloxan diabetes ; intestinal villus ; alkaline phosphatase ; sucrase ; epithelial cells ; villus-crypt axis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: 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.
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    URL: http://dx.doi.org/10.1007/BF01966159
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    Effects of β-hydroxybutyrate on rat embryos grown in culture (1985)
    Springer
    Cellular and molecular life sciences 41 (1985), S. 273-275 
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    ISSN: 1420-9071
    Keywords: Rat ; embryo ; embryo ; rat ; β-hydroxybutyrate ; diabetes ; maternal ; fetal malformation ; malformation ; fetal ; ketone bodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: 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.
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    URL: http://dx.doi.org/10.1007/BF02002633
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    Pharmacokinetics of penbutolol and its metabolites in renal insufficiency (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 215-219 
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    ISSN: 1432-1041
    Keywords: penbutolol ; renal impairment ; beta-adrenoceptor blocking agents ; metabolism ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of penbutolol, its 4-hydroxylated metabolite and of their conjugates was studied in hypertensive patients with various degrees of renal impairment. A single oral dose of penbutolol 40 mg, was rapidly absorbed after a lag-time of 0.34 h. Its plasma concentration reached a maximum after 0.84 h and then declined bi-exponentially, with an apparent elimination half-life of 21.8 h. The hydroxylation of penbutolol was negligible and conjugation was of major importance for its elimination. Consequently, the kinetics of unchanged penbutolol were not altered by renal impairment. The 48 h-urinary excretion of penbutolol and its metabolites reached 13–14% of the administered dose, which is consistent with extensive metabolism of the drug. After treatment for 30 days with penbutolol 40 mg/d there was no accumulation of the parent drug but the concentration of its conjugates was increased. It is concluded that the dose of penbutolol need not be changed in patients with mild renal insufficiency, 4-hydroxypenbutolol is unlikely to participate in the anti-hypertensive effect of the drug, due to its low concentrations, and biotransformation of penbutolol may be enhanced during chronic treatment.
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    URL: http://dx.doi.org/10.1007/BF00547425
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    Pharmacokinetics of fenfluramine and norfenfluramine in volunteers given d- and dl-fenfluramine for 15 days (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 221-224 
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    ISSN: 1432-1041
    Keywords: fenfluramine ; norfenfluramine ; isomers ; pharmacokinetics ; healthy volunteers ; chronic treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of accumulation and elimination of d- and l-fenfluramine (F) and norfenfluramine (NF) have been studied in 8 young healthy volunteers given daily doses of 60 mg of sugar-coated tablets of 20 mg dl-F hydrochloride (dl-F) t.i.d. and capsules of 15 mg d-F hydrochloride (d-F) b.i.d. for 15 days. Repeated doses of d-F plus l-F gave the same values for the parameters measured as did d-F administered alone. Steady-state concentrations of all compounds were achieved within 4–8 days. The predicted mean steady-state concentrations of d-F and elimination half-lives calculated from the results of a previous single dose study were similar to those measured at steady state in this study, confirming the lack of effect of the drug on hepatic microsomal enzymes and on kinetics after repeated dosing. d-NF concentrations were approximately half those of the parent drug and the half-life was almost twice as long. Steady state concentrations both of L-f and l-NF were consistently about 40–50% higher than of the d-isomers and there was a comparable in the half-life.
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    Comparison of the pharmacokinetic profile of metaclazepam in old and young volunteers (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 247-249 
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    ISSN: 1432-1041
    Keywords: metaclazepam ; benzodiazepines ; (KC-2547) ; N-desmethyl-methaclazepam KC-3755) ; pharmacokinetics ; old and young volunteers ; side-effects ; age effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single-centre, open, Phase I-study comparison of the pharmacokinetics of a single dose of metaclazepam 10 mg, a new 1,4-benzodiazepine has been done in 10 older and 20 younger volunteers. No important age-related effect was found on the kinetics of metaclazepam or its N-desmethyl derivative, the principal metabolite in man.
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    URL: http://dx.doi.org/10.1007/BF00547431
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    Pharmacokinetic study of a paediatric formulation of amoxycillin and clavulanic acid in children (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 235-239 
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    ISSN: 1432-1041
    Keywords: amoxycillin ; clavulanic acid ; pharmacokinetics ; side-effects ; paediatric formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A combination of amoxycillin and clavulanic acid 4:1 was administered to 35 children (aged 2 to 10 years) with infections. The combination was administered orally as a suspension, every 8 h for 5 to 7 days. Sixteen children (aged 2 to 5 years), received 125 mg amoxycillin and 31.25 mg clavulanic acid, and 19 (6 to 10 years) received 250 mg amoxycillin and 62.5 mg clavulanic acid per dose. Following the first dose serum concentrations of amoxycillin and clavulanic acid were determined by microbiological assay. In the younger group receiving the lower dosage (mean: amoxycillin 9.11 mg/kg and clavulanic acid 2.34 mg/kg), the mean peak concentration of amoxycillin was 3.5 mg/l and of clavulanic acid 1.2 mg/l, occurring 1.32 h and 1.39 h, respectively, after administration. In the older group receiving the higher dosage (mean: amoxycillin 12.35 mg/kg and clavulanic acid 3.14 mg/kg) the mean peak serum level of amoxycillin was 4.0 mg/l and of clavulanic acid 1.3 mg/l, occurring 1.43 h and 1.23 h, respectively, after administration. The higher dose per kilogram body weight resulted in a higher peak serum concentration both of amoxycillin and clavulanic acid. The formulation was well tolerated by all the children and no serious side-effects were recorded. Treatment was considered clinically effective in all cases.
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    Protein binding and disposition of lignocaine in the elderly (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 323-329 
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    ISSN: 1432-1041
    Keywords: lignocaine ; pharmacokinetics ; proteinbinding ; indocyanine green ; ageing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single dose studies were performed in six young and six elderly nonsmokers using lignocaine as a model drug with high intrinsic clearance. Subjects received lignocaine 250 mg orally and 50 mg intravenously in random order and drug concentrations in blood and plasma were measured for up to 8 h after dose. Protein binding was estimated at 37 °C by equilibrium dialysis. Indocyanine green kinetics were also calculated in each individual following 0.15 mg/kg intravenously. Bioavailability of lignocaine was greater in the elderly but there was no apparent difference in the rate of absorption. Intrinsic clearance of lignocaine was lower in the aged. Elimination half-life was longer in the elderly but there was no significant difference in apparent volume of distribution or systemic clearance of lignocaine. Plasma clearance of indocyanine green showed no correlation with systemic lignocaine clearance and was lower in the aged subjects. Blood/plasma lignocaine ratio was less than unity in both groups. Binding of lignocaine to plasma proteins showed concentration-dependence and was higher in the geriatric group. Maximum binding capacity of lignocaine was greater in the elderly but the binding affinity did not significantly change with age. Greater oral bioavailability of drugs like lignocaine may produce higher plasma concentrations in the elderly. Unlike indocyanine green, the systemic clearance of lignocaine was unaltered by age in this group of non-smokers. The protein-binding of lignocaine, like many other basic drugs, is increased in elderly subjects.
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    Pharmacokinetics of pefloxacin in renal insufficiency (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 345-349 
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    ISSN: 1432-1041
    Keywords: pefloxacin ; renal insufficiency ; pharmacokinetics ; haemodialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of pefloxacin has been studied after a single intravenous infusion of 8 mg·kg−1 in 15 male patients with various degrees of renal failure. No difference in distribution or elimination of the drug was observed between patients with mild or severe renal impairment. The mean volume of distribution (Vd area) and the mean plasma clearance were 2.03l·kg−1 and 121.3 ml·min−1, respectively. The mean apparent elimination half-life was 13.5 h. These values are close to those observed in healthy subjects. No accumulation of the active N-desmethylmetabolite was observed in cases of severe failure as compared to mild impairment; its apparent elimination half-life was about twice that of the parent drug. The efficacy of a 4 h haemodialysis in 6 additional anuric subjects done to remove pefloxacin from the body was poor.
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    Ro 31-1118, a new cardioselective β-adrenoceptor antagonist (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 395-399 
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    ISSN: 1432-1041
    Keywords: Ro 31-1118 ; cardioselectivity ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five patients with mild hypertension were given single oral doses of Ro 31-1118 (10, 20, 40, and 80 mg) and placebo in a randomized, double-blind, within-patient study. Plasma concentrations of Ro 31-1118 and supine, standing, exercise, and post-exercise heart rates and blood pressures were measured before and at regular intervals after drug administration. The pharmacokinetic data were consistent with a one-compartment model with first-order absorption and a variable time lag. Peak plasma concentrations and area under curve were linearly related to dose, whereas time to peak concentration, half-time, clearance and apparent volume of distribution were dose-independent. There was a reduction in exercise and post-exercise heart rate of approximately 10% after 10 mg and 20 mg Ro 31-1118, and of approximately 15% after 40 mg and 80 mg. At all doses standing systolic blood pressure was reduced by approximately 5%. A similar fall was seen in exercise and post-exercise systolic blood pressures. There was no substantial effect of Ro 31-1118 on supine or standing heart rates nor on diastolic blood pressure. No adverse effects were reported. It is concluded that Ro 31-1118 has linear pharmacokinetics over the dose range 10–80 mg, and has a weak antihypertensive effect when administered in single doses to patients with mild hypertension.
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    Pharmacokinetics of amiodarone, desethylamiodarone and other iodine-containing amiodarone metabolites (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 417-423 
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    ISSN: 1432-1041
    Keywords: amiodarone ; desethylamiodarone ; iodine ; pharmacokinetics ; thyroid function ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 23 patients treated with the iodine-containing antiarrhythmic drug amiodarone, the plasma concentrations of amiodarone, desethylamiodarone and iodine have been studied. Besides amiodarone and desethylamiodarone, a pool of iodine-containing substances, NANDAI (non-amiodarone-, non-desethylamiodarone-iodine), was present. At steady state the iodine content of NANDAI amounted to 64% and the iodine content of amiodarone plus desethylamiodarone to 36% of total serum iodine. At steady state 26% of the NANDAI fraction was made up of inorganic iodide, the average plasma concentration of which was at least 40 times above the upper limit of the normal range. The serum elimination half-life of NANDAI of 57–160 days exceeded that of amiodarone (35–68 days) and of desethylamiodarone (31–110 days). At steady state the serum concentration of desethylamiodarone appears to be related to the concentration of amiodarone by a Michaelis-Menten type function, yielding a Km of amiodarone of 2.45 µmol/l and a maximal desethylamiodarone concentration of 3.61 µmol/l.
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    Baclofen in the elderly stroke patient its side-effects and pharmacokinetics (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 467-469 
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    ISSN: 1432-1041
    Keywords: baclofen ; stroke ; elderly patients ; pharmacokinetics ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double blind crossover trial of baclofen against placebo in elderly stroke patients was discontinued because the drug produced an unacceptably high level of drowsiness. In a subsequent study baclofen 10 mg was given orally to 12 elderly stroke patients, and drug concentrations measured from a series of plasma samples. A group of healthy subjects given the same dose in a previous study were used as controls. Elderly patients took longer to achieve peak plasma baclofen concentrations, but healthy controls had higher peak values and eliminated the drug more rapidly; areas under the curve were similar in the two groups. Simulations based on mean data suggest that increased drowsiness in the elderly was probably not due to changes in the drug's pharmacokinetic behaviour.
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    Pharmacokinetics of carteolol in relation to renal function (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 461-465 
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    ISSN: 1432-1041
    Keywords: carteolol ; chronic renal failure ; pharmacokinetics ; dosage adjustment ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma levels and urinary excretion of carteolol and its main metabolites 8-hydroxycarteolol and carteolol glucuronide were investigated in 6 healthy subjects and 9 patients with varying degrees of renal impairment following a single oral dose of 30 mg carteolol hydrochloride. In healthy subjects the half-life of carteolol was 7.1 h. 63% of the administered dose was recovered unchanged in urine, and in all 84% was excreted by the kidneys. The renal clearance of carteolol was 255 ml/min. In chronic renal failure (CRF) the terminal half-life was increased to a maximum of 41 h. Both the elimination rate constant and renal clearance were closely related to the creatinine clearance. In CRF the recovery of carteolol and its metabolites from urine was considerably reduced, suggesting that another pathway of drug elimination becomes relevant in renal disease. To avoid an increase in side-effects due to drug accumulation, the dosage of carteolol should be adjusted in relation to the reduction in creatinine clearance. The maintenance dose should be reduced to a half in patients with a creatinine clearance below 40 ml/min and above 10 ml/min. In those with a creatinine clearance of 10 ml/min or less, the dose should be reduced to 1/4.
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    Separate and combined effects of nadolol and nifedipine on the cardiac response to exercise (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 113-117 
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    ISSN: 1432-1041
    Keywords: nadolol ; nifedipine ; tachycardia ; cardiovascular response ; healthy volunteers ; pharmacokinetics ; exercise heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a placebo controlled exercise protocol using healthy volunteers the effects of nadolol 80 mg and 160 mg orally and of nadolol 80 mg during treatment with nifedipine 20 mg 8 hourly were compared. Resting systolic and diastolic blood pressures were reduced by both nifedipine (p〈0.05) and nadolol (p〈0.01) acting alone. An unexpected finding was that nifedipine alone significantly inhibited exercise tachycardia (p〈0.01) (8 to 12 h post dose). Predictably both doses of nadolol produced significant reduction in exercise tachycardia which was still apparent at 24 h. There was a linear relationship between log10 plasma nadolol concentration and reduction in exercise heart rate. The combined inhibitory effects of nifedipine and nadolol 80 mg on exercise heart rate showed partial additivity but did not summate. There was no pharmacokinetic interaction between the 2 drugs. The inhibition of exercise tachycardia by nifedipine, not previously documented, is consistent with an effect of the drug on the sinus node, as has been reported in in-vitro studies, and may contribute to the drugs efficacy in angina.
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    URL: http://dx.doi.org/10.1007/BF00609676
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    Pharmacokinetic study of IV infusions of adriamycin (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 205-212 
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    ISSN: 1432-1041
    Keywords: adriamycin ; cancer patients ; infusion ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma pharmacokinetics of adriamycin has been studied in 21 cancer patients (31–85 years old) without liver tumours after short (3.00 min) and prolonged (45 min-16h) i.v. infusions. The area under the plasma concentration-time curve and the maximum plasma concentration compensated for dose variation showed a more than 3-fold individual variation. The pharmacokinetics of adriamycin was linear. There was no pharmacokinetic rational for variation of the dose with the age of the patients. There was good agreement between the measured plasma concentration-time curves for prolonged infusions and curves predicted from pharmacokinetic data from short term infusions.
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    Effect of concomitant food intake on absorption kinetics of erythromycin in healthy volunteers (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 231-233 
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    ISSN: 1432-1041
    Keywords: erythromycin ; pharmacokinetics ; steady-state ; food effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady state absorption of erythromycin from enteric-coated pellets of erythromycin base was compared with that from enteric-coated tablets in a randomized, two-way cross-over study in 24 healthy adult volunteers. A higher mean individual peak concentration (p〈0.01), and a greater mean area under the serum concentration-time (0–8 h) curve (AUC,p〈0.01) was produced by the enteric-coated pellets, when the preparations were administered 1 hour before breakfast. No significant differences in the kinetic parameters between the two preparations were observed when they were taken during a non-standardized breakfast, as concomitant food intake was found to reduce both the peak levels and the AUC-values (p〈0.01) produced by the pelleted preparation.
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    URL: http://dx.doi.org/10.1007/BF00609699
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    Single-dose and steady-state pharmacokinetics of piroxicam in elderly vs young adults (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 305-309 
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    ISSN: 1432-1041
    Keywords: piroxicam ; pharmacokinetics ; geriatrics ; renal insufficiency ; drug safety ; non-steroidal anti-inflammatory drugs ; osteoarthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Age-dependent changes in pharmacokinetics are considered a possible factor contributing to a higher risk of side-effects from drug treatment in the elderly. However, very little is known about the kinetics and metabolism of most NSAI agents in geriatric subjects. In a prospective age-comparison study, the single dose and steady-state pharmacokinetics of piroxicam 20 mg once daily were determined in 44 subjects ranging in age from 30 to 80 years. Plasma concentrations, elimination half-life, AUC, and volume of distribution were not influenced by age or sex and were in agreement with previously reported results in young adults. Pharmacokinetic parameters in 18 patients with evidence of mild or moderate renal impairment at study entry were not different from those in patients without impairment. Based on this and other studies, elderly patients receiving the recommended dose of piroxicam are not exposed to undue risk related to pharmacokinetic considerations.
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    Effect of probenecid on isofezolac kinetics (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 433-437 
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    ISSN: 1432-1041
    Keywords: isofezolac ; probenecid ; pharmacokinetics ; anti-inflammatory drug ; drug interaction ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The interaction between isofezolac and probenecid has been studied with the aid of a specific HPLC assay for isofezolac in plasma and urine. 8 healthy adult volunteers received a single 40 mg oral dose of isofezolac before and after 3 days of loading with 0.5 g probenecid t.i.d. There was an increase in the maximum plasma isofezolac concentration from 2.44 to 3.38 µg · ml−1 when probenecid was given. The AUC of isofezolac in plasma increased from 6.73 to 11.28 µg · h · ml−1. After the last dose in a 7 day treatment with 40 mg isofezolac t.i.d., there was an increase in the maximum plasma isofezolac level from 2.84 to 4.96 µg · ml−1 when probenecid was given. The rate of absorption of isofezolac was not affected. An increase in the AUC of isofezolac in plasma was observed from 11.74 to 26.34 µg · h · ml−1. The major effect of probenecid on isofezolac metabolism was a 50% reduction in total isofezolac (free+conjugates) excreted inurine. Because of this interaction, patients given isofezolac combined with probenecid will have a higher steady-state plasma level of isofezolac than when probenecid is not administered.
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    Influence of renal failure on the kinetics of zimeldine and norzimelidine (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 453-456 
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    ISSN: 1432-1041
    Keywords: zimeldine ; norzimelidine ; pharmacokinetics ; renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of zimeldine (Z) and its demethylated metabolite, norzimelidine (NZ), were determined after administration of a single 200 mg oral dose of Z to 6 healthy volunteers (Group I), and to patients with mild (Group II) and severe renal failure (Group III). Z and NZ concentrations were assayed by HPLC in serial plasma and urine samples over 6 days following the dose. In Group I Z was rapidly absorbed and metabolized into NZ, and then the plasma concentrations declined with apparent elimination half-lives of 8.4 h and 24.9 h for Z and NZ respectively, whilst the renal clearance of both compounds was low, Z 15.7 ml/min and NZ 33.0 ml/min. The plasma level of Z differed little between Groups I and III, but the area under the curve was significantly higher in Group III than in Group I subjects (AUC0–144=17.3 and 6.8 µmol·l−1·h, respectively). Severe renal failure did not affect the peak plasma concentration of NZ but it did significantly increase peak time, apparent elimination half-life, and the area under the plasma concentration curve. A significant inverse relationship was found between renal clearance of NZ and plasma creatinine. Since NZ is as pharmacologically potent as Z, the results suggest that the dose of Z should be reduced in patients with severe renal insufficiency.
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    Evaluation of infusion regimens for thiopentone as a primary anaesthetic agent (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 543-552 
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    ISSN: 1432-1041
    Keywords: thiopentone ; anaesthesia ; intravenous anaesthesia ; multi-stage infusion ; exponential infusions ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Several multi-stage infusion regimens and a computer controlled exponentially decreasing infusion regimen were evaluated in twelve patients undergoing head and neck surgery or neurosurgery. Thiopentone dosage was based on the mean of pharmacokinetic parameter values from the literature and adjusted for each patient's lean body mass in order to rapidly achieve a predetermined plasma thiopentone concentration of 15 or 20 µg/ml in the period following the initial bolus dose to induce anaesthesia. Anaesthesia was satisfactory in all cases. Plasma thiopentone concentrations were maintained between 10–20 µg/ml during infusion in the five patients who received either a four or five stage infusion and in the six patients who received the exponential infusion, but not in the single patient who received a two-stage infusion. The mean recovery time was 111 min. The plasma concentrations of total and unbound thiopentone at awakening showed little intersubject variability, despite considerable differences in total dose and duration of infusion, suggesting the absence of acute tolerance to the drug. Plasma clearance of total thiopentone correlated strongly with calculated lean body mass and to a lesser extent with total body weight suggesting that lean body mass, in particular, should be an accurate predictor of thiopentone maintenance dose requirements. This study shows that it is feasible to use thiopentone as a primary anaesthetic agent during surgery by administering the drug either as an exponentially decreasing infusion or as an infusion comprising 4 or 5 stepwise decreasing rates.
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    The pharmacokinetics and haemodynamics of BTS 49465 and its major metabolite in healthy volunteers (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 659-664 
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    ISSN: 1432-1041
    Keywords: BTS 49465 ; hypertension ; pharmacokinetics ; blood pressure effect ; heart rate effect ; side-effects ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and haemodynamic effects of a 200 mg oral dose of BTS 49465 (7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) were investigated in a double-blind placebo controlled study. BTS 49465 was rapidly absorbed and cleared from the systemic circulation with a half-life of 1.6 h by oxidation to the sulphone metabolite. The metabolite was cleared with a half-life of 37.6 h. Saliva concentrations of both BTS 49465 and its metabolite correlated well with the plasma concentrations. Compared to placebo, BTS 49465 produced statistically significant reductions in blood pressure and increases in heart rate both supine and after a 60° head up tilt. The time course of the haemodynamic changes suggested that the sulphone metabolite contributed to the overall hypotensive response. Plasma Renin Activity was only marginally elevated and there was no evidence of acute fluid retention. BTS 49465 was well tolerated in terms of haematological and biochemical parameters and subjective side-effects.
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    Antipyrine metabolite formation and excretion in patients with chronic renal failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 589-595 
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    ISSN: 1432-1041
    Keywords: antipyrine ; chronic renal failure ; drug metabolism ; metabolism ; cumulation ; renal excretion ; pharmacokinetics ; clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In the present study the influence of chronic renal insufficiency on antipyrine clearance, metabolite formation and excretion was investigated in 8 patients. After oral administration of antipyrine, the parent compound, its metabolites and their conjugates were assayed in plasma and urine. Besides the parent drug, 3-hydroxymethylantipyrine (HMA) was present in plasma in the free and conjugated forms, whereas 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) were found only in the conjugated form. The same was true for urine. The plasma concentrations of these metabolites are too low to be measured in subjects with normal renal function. Plasma antipyrine clearance in the patients was in the same range as in healthy subjects. Investigation of metabolite kinetics, however, revealed that the rate of formation of NORA was preferentially decreased, whereas that of OHA and HMA were unaltered. Renal clearance of the metabolites of antipyrine was severely impaired in patients with renal insufficiency, and the resulting accumulation made it possible for the first-time to measure the antipyrine metabolites in plasma. Mean residence times of metabolites were longer than that of the parent compound. Renal clearances of the conjugates were correlated with the creatinine clearance, but were somewhat higher. Renal clearance of free HMA was lower and was also correlated with creatinine clearance. The mean clearance for glucuronidation of HMA was 93.1 ml/min. The results suggest that in healthy subjects Phase I metabolism is the rate-limiting step in the elimination of antipyrine, which is essential for its application as a model drug in metabolism studies.
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    Acute and subacute effects on psychomotor performance of femoxetine alone and with alcohol (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 641-647 
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    ISSN: 1432-1041
    Keywords: Femoxetine ; alcohol interaction ; psychomotor performance ; pharmacokinetics ; amitriptyline ; plasma 5HT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects on human psychomotor performance of femoxetine (FEMO), a 5-hydroxytryptamine-selective antidepressant, alone and in combination with alcohol (EtOH) were compared with those of amitriptyline (AMI) and placebo in a controlled double-blind crossover trial in 11 student volunteers. Objective measurements (body sway, choice reaction, flicker fusion, tracking, nystagmus, digit symbol substitution, backwards recall) and subjective self-assessment (visual analogue scales, reporting of side-effects) were done after single doses of FEMO, AMI and placebo, and subacute administration of FEMO and placebo. Single doses of 200 mg FEMO did not impair psychomotor performance, but 50 mg AMI did so in several respects. AMI but not FEMO increased the objective and subjective effects of EtOH. After FEMO 600 mg/d for 10 days almost no objective difference from placebo was noted, although mild sedation at home was reported as a side-effect. FEMO either did not increase or slightly decreased the effect of EtOH on reactive and co-ordination skills. The plasma concentrations of FEMO varied widely from 0 to 156 ng/ml, as in previous clinical trials but reduced a blood 5-hydroxytryptamine concentration in each subject indicating an effect of FEMO on serotoninergic mechanisms.
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    Pharmacokinetics and metabolic effects of glibenclamide and glipizide in type 2 diabetics (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 697-704 
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    ISSN: 1432-1041
    Keywords: glibenclamide ; glipizide ; pharmacokinetics ; metabolic effects ; Type 2 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen Type 2 diabetics were treated for 4-week periods with once daily (10 mg) glibenclamide, glipizide and placebo according to a double-blind cross-over protocol. Post-dose glipizide concentrations were three times higher than those of glibenclamide, due to the incomplete bioavailability of the latter. On the other hand, pre-dose drug levels were similar, as an expression of the slower absorption and/or elimination of glibenclamide. Both active treatments reduced postprandial blood glucose concentrations and 24-hour urinary glucose excretion to a similar degree, but fasting blood glucose concentrations were slightly lower during glibenclamide treatment. Both active treatments enhanced fasting and postprandial insulin and C-peptide concentrations, the C-peptide response being greater after glipizide than after glibenclamide. Plasma glucagon and GIP concentrations were not significantly affected. Insulin sensitivity was increased by glibenclamide but not by glipizide. Neither therapy affected insulin binding to erythrocytes. It appears that both glibenclamide and glipizide improved glucose metabolism by sustained stimulation of insulin secretion, which was most pronounced with glipizide. Only glibenclamide improved insulin sensitivity and was slightly more active than glipizide on fasting blood glucose levels. The differences may be consequences of the pharmacokinetics, but differences in pharmacodynamics cannot be excluded.
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    Pharmacodynamic and pharmacokinetics of BW 825C: A new antihistamine (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 197-204 
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    ISSN: 1432-1041
    Keywords: triprolidine ; BW 825C ; pharmacokinetics ; pharmacodynamics ; sedation ; intradermal histamine ; human performance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The new H1-receptor antagonist BW 825C and triprolidine (2.5 and 5 mg) were administered to 12 healthy male volunteers in a double blind placebo controlled, balanced, crossover design. Histamine antagonism was measured by assessment of flare and weal areas after intradermal injection of histamine. The 2 compounds were approximately equipotent in blocking the flare and weal response to intradermal histamine and had a similar duration of action. Triprolidine impaired performance of vigilance and reaction time (p〈0.05) compared with placebo while BW 825C did not. Drowsiness measured using visual analogue scales followed both triprolidine treatments, but not BW 825C. BW825C had a plasma half-life (t1/2) of 1.7±0.2 h and triprolidine of 4.6±4.3 h. The peak plasma level of BW 825C was approximately 6 times that of triprolidine. It was concluded that BW 825C might be a clinically active H1-antagonist with reduced sedative side-effects.
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    Food reduces the rate but not the extent of the absorption of theophylline from an aqueous solution (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 225-227 
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    ISSN: 1432-1041
    Keywords: theophylline ; absorption ; food intake ; aqueous solution ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of food on the rate and extent of absorption of theophylline was studied in healthy adults given a single dose of theophylline (aqueous solution of choline theophyllinate containing 270 mg of theophylline) in the evening either on an empty stomach or together with supper. Food appeared to decrease the absorption rate of theophylline significantly, tmax being prolonged from 1.34 h (mean) to 4.40 h and cmax decreased from 7.82 mg·l−1 to 5.47 mg·l−1. The area under the plasma concentration-time curve (AUC) after drug intake with supper was slightly but not significantly smaller, indicating that theophylline (as a solution of choline theophyllinate) can be taken together with food without substantial loss of the quantity of drug absorbed. The elimination rate was not influenced by concomitant intake of supper.
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    Pharmacokinetics and plasma-concentration-effect relationships of prenalterol in cardiac failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 397-403 
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    ISSN: 1432-1041
    Keywords: prenalterol ; cardiac failure ; pharmacokinetics ; concentration-effect relationships
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prenalterol was administered as an intravenous infusion at three incremental rates (60, 120 and 240 nmol/min) to five patients with severe cardiac failure. Haemodynamic, hormonal and metabolic variables were measured at the same time as plasma prenalterol concentrations, and the pharmacokinetics of the drug were studied by following plasma concentrations and urinary excretion during and after the infusion. Concentration-dependent increases in cardiac index, stroke index and stroke work index were observed without increases in arterial pressure, heart rate or myocardial oxygen demand. The reninangiotensin-aldosterone system was stimulated, although the extent of stimulation varied among patients. No strong correlations were found between the logarithm of the plasma prenalterol concentration and effect. Plasma clearance of the drug was lower in cardiac patients than in normal volunteers, but a large decrease in renal clearance was partially balanced by an increase in nonrenal clearance. Over the observed range of concentrations, no deviation from linearity was evident, and plasma concentrations of about 150 nmol/l were effective in improving cardiac function without significant side-effects.
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    Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 425-428 
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    ISSN: 1432-1041
    Keywords: caffeine ; oral contraceptives ; pharmacokinetics ; elimination half-life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of chronic (〉3 months) administration of low-dose oestrogen-containing (〈50 µg oestrogen) oral contraceptives (OCS) on the pharmacokinetics of caffeine has been examined in a treated females matched with 9 non-smoking, drug-free, healthy control females of similar age, weight and ethnic origin. Each subject received 162 mg caffeine base orally after an overnight fast. OCS subjects had a prolonged elimination half-life of caffeine, (mean 7.88 h vs 5.37 h in the controls). This was the result of marked impairment of the plasma clearance of caffeine (1.05 vs 1.75 ml/min/kg, respectively) with no change in apparent volume of distribution (0.685 in OCS vs 0.750 l/kg in the control group). The absorption parameters determined were peak plasma caffeine concentration (3.99 vs 4.09 µg/ml) and time to peak concentration after drug administration (1.52 vs 0.79), which was moderately prolonged in OCS users. Thus, caffeine clearance, previously reported to be a specific marker of cytochrome P-448 activity in man, is decreased by chronic OCS use. This suggests that OCS may cause significant impairment of this enzyme activity as assessed in vivo. With chronic caffeine consumption, OCS users are predicted to have an increased steady-state plasma caffeine concentration as compared to non-OCS users.
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    Personality and theophylline pharmacokinetics (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 429-431 
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    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; personality measures ; pharmacokinetics ; volunteers ; patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirteen volunteers received an iv dose of theophylline followed by blood sampling for 8 h to calculate pharmacokinetic parameters. Ten patients with asthma undergoing chronic dosing with slow release aminophylline underwent 12 h of blood sampling to calculate theophylline clearance. Both groups completed an Eysenck Personality Inventory (EPI) from which was derived scores for neuroticism (N) and extroversion (E). Using multiple regression analysis no independent effect of either N or E score on theophylline clearance or half-life could be demonstrated.
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    Pharmacokinetics of acetohydroxamic acid in patients with staghorn renal calculi (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 439-445 
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    ISSN: 1432-1041
    Keywords: acetohydroxamic acid ; staghorn renal calculi ; pharmacokinetics ; 14C-labeled drug ; acetamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetohydroxamic acid (AHA), a bacterial urease inhibitor, has been recently approved by the United States Food and Drug Administration as a potential drug for the successful treatment of patients with infection induced staghorn renal calculi. The present study was designed to evaluate the disposition of 14C-AHA following oral administration to patients. The results of the study, while in a limited number of patients, indicate that upon oral administration, AHA is very rapidly absorbed from the gastrointestinal tract. Evaluation of urinary excretion data suggests that patients with compromised renal function have low recoveries of AHA in the urine. These data are supported by a strong linear correlation between creatinine clearance and AHA elimination. Acetamide and CO2 are identified as the two major metabolites of AHA in man. CO2 is eliminated in the breath and accounts for 20–45% of the administered dose, while acetamide is eliminated in the urine and accounts for only 9–14% of the administered dose. The remaining dose is eliminated as intact AHA in the urine (19–48%). Saliva concentrations of total radioactivity depict a strong positive correlation with their respective plasma concentrations. Parameter estimates from 14CO2 concentrations in breath as a function of time data closely correspond to the pharmacokinetic parameters of AHA in patients indicating that CO2 may be a primary metabolite derived directly from AHA rather than a secondary metabolite formed by the metabolism of an intermediate product. Upon multiple dose administration of AHA, there is the potential for significant accumulation of acetamide due to its relatively long half-life.
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    Clinical pharmacokinetics of 6-hour infusion of high-dose methotrexate. Preliminary trial of monitoring high infusion doses (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 457-462 
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    ISSN: 1432-1041
    Keywords: methotrexate ; osteosarcoma ; high parenteral dose ; pharmacokinetics ; drug monitoring ; computer prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Methotrexate (MTX) in serum was measured by RIA in 12 cancer patients receiving high doses of MTX (2 to 8 g/m2) in 6 hour infusions 69 treatments were studied. The peak serum level was proportional to the dose administered and was always greater than 10−4 M. 2 elimination phases were seen: the first had a mean half-life of 2.36 h and the second a mean half-life of 16.14 h. 24 hours after beginning the infusions there were very large variations in individual serum concentrations of MTX, from 2.4 10−6 M to 1.9 10−5 M by 24 h after 8 g/m2. To control these variations, a mathematical model for prediction of the individual pharmacokinetic pattern of a 6 hour-infusion of high-dose MTX by kinetic analysis of a low-test dose is proposed. A program was created for an Apple III computer using toxic and therapeutic serum levels of MTX selected by the clinician. The computer program is adaptable to any infused substance for variable infusion times, thus introducing new advances over existing methods.
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    Pharmacokinetics of tocainide in patients with severe renal failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 665-670 
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    ISSN: 1432-1041
    Keywords: tocainide ; renal failure ; pharmacokinetics ; oral dosing ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma levels of tocainide have been followed after oral administration of 600 mg p.o. to 20 patients with renal failure due to various causes, and to 8 healthy controls. The peak plasma concentrations in the patients with pyelonephritis (3.80 µg/ml) and interstitial nephritis (3.74 µg/ml) but not in those with glomerulonephritis (3.17 µg/ml) differed from that in healthy volunteers (3.24 µg/ml). The renal clearance of tocainide was well correlated with the endogenous creatinine clearance and was dependent on urine pH. No difference in renal clearance was observed between the patients groups. It is suggested that the changes in plasma levels are a consequence of decreased renal clearance. Creatinine clearance was shown to be a poor estimator of tocainide clearance, which suggests that extrarenal clearance plays an important role in the handling of the drug in the body. The findings are used to suggest a safe dosage regimen.
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    Further support for changes in chloroquine disposition and metabolism between a low and a high dose (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 721-722 
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    ISSN: 1432-1041
    Keywords: chloroquine ; rheumatoid disease ; desethylchloroquine ; capacity limitation ; pharmacokinetics ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of chloroquine and its major metabolite desethylchloroquine were studied in patients with rheumatoid disease after single oral doses of chloroquine phosphate corresponding to 150 and 300 mg chloroquine base. The findings strengthen the previous finding that the disposition of chloroquine involves rate limiting steps.
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    Pharmacokinetics of oral moclobemide in healthy human subjects and effects on MAO-activity in platelets and excretion of urine monoamine metabolites (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 89-95 
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    ISSN: 1432-1041
    Keywords: moclobemide ; Ro 11-1163 ; pharmacokinetics ; bioavailability ; MAO activity in platelets ; monoamine metabolites in urine ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of the MAO-inhibitor moclobemide (Ro 11-1163) were determined in six healthy male subjects after oral (tablets) administration. Effects on MAO activity in platelets and excretion of monoamine metabolites in urine were investigated. The design of the study was a double-blind cross-over study with single oral doses of placebo, 50, 100 and 200 mg of moclobemide. The elimination profile of the drug showed that the half life of the unchanged drug ranged between 1 and 2 h except in one subject with a half-life of about 4 h. The mean bioavailability calculated using flow model concepts was F=0.43 after 50 mg, F=0.47 after 100 mg and F=0.59 after 200 mg. The outlier with a t1/2 of 4 h was found to have a bioavailability of more than 0.80 after all 3 doses. The slightly increasing bioavailability with higher doses was interpreted as evidence of saturable hepatic first-pass elimination of the drug. MAO activity in platelets was measured before and 2, 6 and 24 h after drug administration. No inhibition of platelet MAO was obtained at any point in time or dose level, as to be expected since moclobemide preferentially inhibits MAO A. Urine excretion of the monoamine metabolites homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxy-phenylglycol (MOPEG) and 5-hydroxyindoleacetic acid (5-HIAA) was followed during 48 h after placebo, 50 and 200 mg of moclobemide. Time but not dose contributed significantly to the variability in excretion of the monoamine metabolites. An apparent reduction of HVA and DOPAC levels was obtained in the early phase after the administration of 200 mg of moclobemide. In 1 subject with a mild drug reaction a pronounced decrease in the levels of all the metabolites was obtained. In the other 5 subjects, the compound was very well tolerated with a few reported side-effects like increased activity, somnolence or sweatings. There was a slight but significant increase in blood pressure following 50 and 100 mg but not 200 mg of moclobemide.
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    Pharmacokinetics of sulphinpyrazone and its major metabolites after a single dose and during chronic treatment (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 97-103 
    Details
    ISSN: 1432-1041
    Keywords: sulphinpyrazone ; metabolism ; single dose ; chronic treatment ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulphinpyrazone and its major metabolites (sulfide, sulfone, p-hydroxysulfone and p-hydroxy-sulphinpyrazone) were investigated in 9 volunteers after a single oral dose as well as after chronic treatment for 23 days. Chronic administration of sulphinpyrazone, in comparison with a single oral dose, led to significant changes in plasma AUC (115.86 to 42.90 mg/l·h), in renal clearance (1.06 to 1.80l/h), in hepatic intrinsic clearance (319.0 to 598.0l/h), and in the unbound fraction in plasma 1.15 to 1.69%) and in tissue (2.73 to 1.31%). The volume of distribution changed from 20.24 to 52.041. The steady state concentrations predicted from the single dose were significantly higher than the values found after chronic treatment. The results suggest that sulphinpyrazone induces its own metabolism. The metabolism of the sulfone, p-hydroxysulfone and the p-hydroxy-sulphinpyrazone to further degradation products was also induced. Chronic treatment with sulphinpyrazone reduced the plasma AUC of the sulfide and caused a decrease in its elimination half-life (20.9 to 14.3 h). Since considerable amounts of the sulfide are formed in the G.I. tract, it is suggested that besides the induction of metabolism, bacteria which reduce sulphinpyrazone to the sulfide may also be responsible for the observed pharmacokinetic changes.
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    Limitation on the use of amiloride in early renal failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 61-66 
    Details
    ISSN: 1432-1041
    Keywords: amiloride ; kidney function ; Na+ ; K+ ; Ca++ ; Mg++ excretion ; renal amiloride clearance ; chronic renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a single oral dose of 10 mg amiloride was studied on urinary excretion of Na+, K+, Ca++ and Mg++ in healthy subjects and in patients with varying degrees of renal impairment. Amiloride produced a moderate diuresis and sodium excretion, and a slight calciuresis. Urinary excretion of potassium was significantly reduced as compared to the controls. Despite its diuretic and natriuretic effects, amiloride did not change the excretion of Mg++ as compared to the pretreatment period. When the creatinine clearance was below 50 ml/min, the net excretion of Na+ and Ca++ was drastically reduced. However, K+ retention and neutrality of Mg++ excretion were maintained down to end-stage renal disease. In the healthy volunteers the mean elimination half-life of amiloride was 20 h, and it rose to about 100 h in end-stage renal disease. This was because about 3/4 of native amiloride was eliminated through the kidney. Nonrenal elimination of amiloride was calculated to amount to only 1/4 of the total elimination. Therefore, the antikaliuretic amiloride is a valuable comedication in subjects with normal kidney function to prevent K+ and Mg++ loss. However, its use is hazardous if plasma creatinine is raised.
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    Pharmacokinetics and metabolism of isosorbide-dinitrate after intravenous and oral administration (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 637-644 
    Details
    ISSN: 1432-1041
    Keywords: isosorbide-dinitrate ; pharmacokinetics ; analytical method ; bioavailability ; drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailabilities of a conventional and two slow release 20 mg isosorbide dinitrate (ISDN) formulations were compared after oral administration in a three way cross-over study in 8 male volunteers. In a further group of 6 male volunteers the pharmacokinetics and metabolism of ISDN were investigated after intravenous infusion of a median dose of 14.1 mg for 2.5 h. A new analytical procedure was developed for the determination of isosorbide-5-mononitrate-2-glucuronide (IS-5-MN-2-Glu) and of isosorbide (IS). Kinetic data analysis on a molar basis was performed by the program package KINPAK providing model independent parameters. The median elimination half-lives of ISDN, IS-5-MN, IS-2-MN and IS-5-MN-2-Glu were 0.7, 5.1, 3.2 and 2.5 h, respectively. The systemic clearance of ISDN was 3.7 l/min and the distribution volume 2521 (3.1 l/kg). Apart from IS-5-MN-2-Glu, with a renal clearance of 5.9 l/min which suggested substantial glucuronidation in the kidney, the renal clearances of ISDN, IS-5-MN, IS-2-MN and the corresponding amounts excreted were negligible. 27.8% of the administered ISDN was excreted as IS-5-MN-2-Glu (8.7%) and IS (19.1%). Calculations based on the two mononitrate metabolites formed from ISDN showed an incomplete recovery of 84.1%, leading to the assumption that a simultaneous denitration to IS must have occurred. The rate of denitration at each nitro group in ISDN was almost twice as high as for the same position in the corresponding mononitrate. The bioavailability of the conventional ISDN formulation was 19%, although complete absorption was indicated by comparison of the percentages of mononitrate metabolites formed after the different routes of administration. On the same basis the absorption of the two sustained release formulations was found to be poor.
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    Comparative β-adrenoceptor blocking effect and pharmacokinetics of bucindolol and propranolol in man (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 649-656 
    Details
    ISSN: 1432-1041
    Keywords: bucindolol ; propranolol ; beta-adrenoceptor blockade ; intrinsic sympathomimetic activity ; vasodilator ; pharmacokinetics ; blood pressure ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The β-adrenoceptor blocking properties and pharmacokinetics of bucindolol 150 mg were compared to those of propranolol 80 mg and a placebo in a double-blind trial in 6 healthy volunteers. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures and peak expiratory flow rate (PEFR) at rest and during vigorous exercise, and plasma renin activity (PRA) at rest, were measured before and at intervals up to 24 h after oral administration of the drugs. Bucindolol reduced exercise tachycardia and decreased exercise PEFR, thus behaving as a non-selective β-adrenoceptor blocking drug. In contrast to propranolol, bucindolol did not reduce resting HR and PRA, probably because of its intrinsic sympathomimetic activity. It decreased resting DBP in relation to its peripheral vasodilator properties. The effects of bucindolol developed as early as 30 min after administration and lasted up to 24 h, whereas its Tmax and T1/2 were 1.6 and 3.6 h respectively. Comparison of the time courses of plasma bucindolol and the cardiac β-adrenoceptor blockade strongly suggests that in man bucindolol undergoes an extensive first-pass effect, leading to the formation of one or more active metabolites.
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    CSF and plasma pharmacokinetics of intramuscular morphine (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 677-681 
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    ISSN: 1432-1041
    Keywords: morphine ; analgesic ; pharmacokinetics ; intramuscular administration ; CSF/plasma-morphine levels ; CSF kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Morphine concentrations in plasma and cerebrospinal fluid (CSF) were measured in 58 elderly patients after intramuscular administration of 10 mg morphine. The assay employed gas chromatography with electron capture detection. From 49 of the patients undergoing urological procedures plasma and lumbar CSF samples were obtained simultaneously as spinal analgesia was given, and in addition, repeated venous samples were obtained over 4 hours from 35 of the patients. A plasma-morphine concentration vs time plot was drawn from the mean values and a CSF-morphine vs time plot was calculated by pooling individual CSF concentrations and using the sliding mean technique. The individual CSF/plasma-morphine concentration ratio vs time was also plotted. In addition, 2 or 3 CSF and plasma samples were collected simultaneously from 3 patients undergoing thoracotomy. Large interindividual variation in the CSF concentration was found. The peak CSF level was reached after 3 h and, following pseudoequilibrium, CSF-morphine levels appeared only slightly lower than those found in plasma. The availability to spinal CSF amounted to no more than 0.005% of the administered dose. CSF-morphine concentrations were not related to plasma protein or albumin concentrations.
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    Pharmacokinetics and distribution of flucloxacillin in pacemaker patients (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 713-719 
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    ISSN: 1432-1041
    Keywords: flucloxacillin ; cardiac pacemaker ; pharmacokinetics ; protein binding ; tissue fluid ; elderly patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of flucloxacillin in plasma and tissue fluid after i.v. infusion of 1 g was analyzed according to an open two-compartment model in 19 patients with bradyarrhythmias (mean age 70.8 years) admitted for implantation or replacement of a permanent pacemaker system. After the first infusion of flucloxacillin (5 min), the distribution phase was rapid (t1/2α=0.13 h). The plasma half-life of elimination (t1/2β) was 1.51 h, which is almost twice as long as reported in healthy volunteers. Total plasma clearance (93.1 ml/min) was also lower than is usually found in healthy individuals, due to low renal clearance of flucloxacillin (60.2 ml/min). The total apparent volume of distribution during the β-phase (Vdarea) was 0.172 l/kg and distribution in the central compartment (Vc) 0.064 l/kg. In each patient plasma protein binding and drug distribution to plasma water, proteins and blood cells in whole blood were determined. Binding in plasma to proteins was 91.0% and distribution to blood cells in whole blood 13.8%. The mean distribution volume of free flucloxacillin during the β-phase (Vdβ free) was 2.18 l/kg, which exceeds total body water, suggesting possible intracellular distribution and substantial tissue binding. Plasma concentrations of flucloxacillin after the fourth dose (1 g t.i.d.) were very similar to those obtained after the first infusion and those predicted from the single dose kinetics. The concentration of flucloxacillin in fluid from the pacemaker pockets in 5 patients averaged 12.1 µg/ml and 9.5 µg/ml at 1 and 5 h, respectively, which was more than ten times the MIC-values for Staphylococcus aureus and S. epidermidis. The average concentration ratio (tissue fluid/plasma) was 0.57. Thus the pharmacokinetics of flucloxacillin in these elderly patients exhibited marked differences from what has been found in healthy volunteers. Despite the high degree of plasma protein binding, flucloxacillin appears to distribute rapidly and efficiently to extravascular compartments, such as a pacemaker pocket.
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    The pharmacodynamics and pharmacokinetics of a new calcium antagonist nisoldipine in normotensive and hypertensive subjects (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 21-24 
    Details
    ISSN: 1432-1041
    Keywords: nisoldipine ; nifedipine ; pharmacokinetics ; pharmacodynamics ; calcium channel blocking drugs ; hypertension ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamic and pharmacokinetic profiles of nifedipine and nisoldipine were compared in a double blind, placebo-controlled study. Nisoldipine, 10 mg significantly reduced systolic blood pressure but nifedipine 20 mg retard did not, although both drugs had significant pharmacodynamic effects as evidenced by increased heart rates. The terminal elimination half-life in plasma was similar for both drugs with a mean of 2 h. The pharmacodynamics of nisoldipine were studied in 8 hypertensives following both acute and chronic administration. Antihypertensive efficacy was demonstrated after acute dosing and was maintained over 4 weeks of twice daily treatment as monotherapy.
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    On the interaction between phenytoin and digoxin (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 49-53 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; digoxin serum concentration ; drug interaction ; digoxin clearance ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An open, randomized, single-blind cross over trial to investigate phenytoin-digoxin interactions at steady state was performed in 6 healthy male volunteers. Coadministration of phenytoin caused a significant reduction in the elimination half-life of digoxin from 33.9 to 23.7 h and a diminution in AUC0–48 from 31.6 to 24.4 ng · ml−1 · h. Renal digoxin clearance was not significantly altered from 135.7 to 120.3 ml · min−1. Assuming no change in β-acetyldigoxin absorption, the in decrease time-course the serum digoxin concentration was due to a significantly increased total digoxin clearance from 258.6 to 328.3 ml · min−1. An insignificant reduction in the digoxin distribution volume from 749.4 to 668.0 l was also observed. No relevant change in the pharmacokinetic parameters (elimination half-life, area under the serum concentration time-curve, protein binding) of phenytoin was observed when phenytoin and digoxin were co-administered. The data suggest that with this drug combination the serum digoxin concentration should be carefully monitored and, if necessary, the daily digoxin dose should be increased.
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    Linear pharmacokinetics of intravenous ergotamine tartrate (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 61-66 
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    ISSN: 1432-1041
    Keywords: ergotamine ; pharmacokinetics ; blood/plasma concentration ratio ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ergotamine tartrate 0.5, 0.25 and 0.125 mg was administered i.v. to 6 volunteers in a cross-over study. Its pharmacokinetic characteristics were evaluated from plasma concentration-time data determined by HPLC. The clearance and volume of distribution were independent of the dose. The ratio between blood and plasma ergotamine concentrations in 4 subjects ranged from 0.41–0.67, indicating the lack of binding to blood cells. Ergotamine was found to be a high clearance drug, average 2.21/min/70kg body wt. suggesting extrahepatic clearance. A possible transient decrease in liver blood flow caused by ergotamine did not seem to affect the linearity of its kinetics.
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    Pharmacokinetics of pirprofen in young volunteers and elderly patients (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 73-77 
    Details
    ISSN: 1432-1041
    Keywords: pirprofen ; arthritic disease ; pharmacokinetics ; elderly patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of pirprofen were measured in 11 elderly arthritic patients and 6 healthy young volunteers at the beginning and end of 8 days treatment with 400 mg doses twice daily. The mean ages of the two groups were 74.5 and 21.8 years, respectively. There were no statistically significant differences in peak concentrations, times to peak, areas under the curve or terminal elimination half-lives between the groups after single dosing. Repeated dosing increased plasma drug concentrations in both groups but the extent was as predicted from the single dose data. Again there were no statistically significant differences between the groups, although pre-dosing plasma concentrations were higher in the elderly compared with the young individuals. The results of this relatively small study suggest that advancing age and arthritic disease appear to have little influence on the pharmacokinetics of pirprofen and no modification in the dosage recommendation in elderly patients without overt renal or hepatic impairment is indicated.
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    Pharmacokinetics of triamcinolone acetonide and its phosphate ester (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 85-89 
    Details
    ISSN: 1432-1041
    Keywords: triamcinolone acetonide ; triamcinolone acetonide phosphate ; pharmacokinetics ; high dose ; glucocorticoids ; renal excretion ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Triamcinolone acetonide in the form of its phosphate ester was given intravenously in two different doses (10 mg/kg and 80 mg). Plasma levels of the ester and triamcinolone acetonide were measured and pharmacokinetic parameters were calculated. The pharmacokinetics both of the phosphate and the free alcohol were dose-dependent. No unchanged ester was found in the urine, indicating complete conversion of the pro-drug. Triamcinolone was not a major metabolite of triamcinolone acetonide in humans. Renal clearance was low and independent of the dose. Only about 1% of the dose was found in the urine as triamcinolone acetonide.
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    Dextropropoxyphene kinetics after single and repeated oral doses in man (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 79-84 
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    ISSN: 1432-1041
    Keywords: dextropropoxyphene ; norpropoxyphene ; pharmacokinetics ; single dose ; multiple dose ; prediction ; saturation ; auto-induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of dextropropoxyphene (DP) and its main metabolite norpropoxyphene (NP) were studied in 6 healthy male subjects after a single oral dose of 195 mg DP HCl, and during and after 12 daily single oral doses of 195 mg DP HCl. The kinetics varied up to five-fold between individuals after the single dose, the apparent mean elimination half-life (t1/2) was 16 h for DP and 29 h for NP. The mean apparent overall plasma clearance (CL) for DP was 2.61/min. There was no systematic difference in DP clearance between the single and multiple doses, but the accuracy of individual predictions from single to multiple doses was poor, probably because of imprecise determinations of the AUC and t1/2 in the single dose experiments. The individual correlation between single and multiple dose kinetics was good for NP, although the predicted plasma levels during steady state were significantly higher than the observed levels (mean AUCss/AUCsd: 0.81). There was no sign of saturation kinetics on repeated administration. In fact, autoinduction, resulting in significantly lower plasma concentrations after treatment for 1 week was found for NP and was indicated for DP. On discontinuing DP after 12 days of treatment, the apparent mean t1/2 of DP was 23 h and of NP 25 h.
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    Dose dependent pharmacokinetics of midazolam (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 91-95 
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    ISSN: 1432-1041
    Keywords: midazolam ; 1-hydroxymethylmidazolam ; pharmacokinetics ; dose proportionality ; benzodiazepine ; healthy volunteers ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were investigated following oral administration of 7.5, 15 and 30 mg doses of midazolam in solution to 12 healthy subjects. Compared to the 7.5 mg dose, the Cmax and AUC parameters of both midazolam and 1-hydroxymethylmidazolam increased proportionally after the 15 mg dose and more than proportionally after the 30 mg dose. The t1/2 for midazolam remained relatively constant between the 7.5 and 15 mg doses whereas it increased slightly but significantly after the 30 mg dose. These data indicated that the pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were linear between the 7.5 and 15 mg oral dose range. However, after the 30 mg dose, the systemic availability of midazolam and the AUC for 1-hydroxymethylmidazolam appeared to be greater than that anticipated from the lower doses, possibly due to saturation of midazolam first-pass metabolism. This ist not expected to have any clinical significance under the conditions of therapeutic use.
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    The disposition of bupropion and its metabolites in healthy male volunteers after single and multiple doses (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 97-103 
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    ISSN: 1432-1041
    Keywords: bupropion ; metabolites ; pharmacokinetics ; single and multiple dose ; side-effects ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of bupropion and 3 of its basic metabolites were determined in 8 young, healthy, male volunteers after single and multiple oral doses of bupropion. Plasma profiles were obtained: 1) after a single 100 mg oral dose of bupropion hydrochloride, 2) following administration of 100 mg 8-hourly for 14 days and 3) again after a single 100 mg dose 14 days later. Plasma concentrations of the parent drug and metabolites were determined by high-performance liquid chromatography. Saliva secretion and pupil diameters were measured, subjective assessments of sleep made using visual analogue scales and side effects, blood counts and biochemistry were monitored. After the first dose mean elimination half lives (t1/2) of bupropion, and metabolites I and II were 8, 19 and 19 h respectively. On repeated administration there was little accumulation of the parent drug and no evidence for induction of its own metabolism. Accumulation of I was consistent with its rate of elimination after single doses while that of II was greater than predicted with prolongation of t1/2 to 35 h. Metabolite III was barely detectable after single doses but its accumulation on multiple dosing was consistent with its long half life (35 h) determined on occasion 2. Saliva secretion was significantly reduced during the multiple dosing period but there were no complaints of dry mouth. Subjective assessments of sleep were not significantly altered though one subject reported vivid dreams. There were no other adverse reactions.
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    Human plasma and skin blister fluid levels of griseofulvin following a single oral dose (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 109-113 
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    ISSN: 1432-1041
    Keywords: griseofulvin ; skin blister fluid levels ; pharmacokinetics ; healthy subjects ; bioavailability ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Griseofulvin and 6-demethylgriseofulvin (6-DMG) in plasma, suction blister fluid (SBF) and cantharides blister fluid (CBF) and urinary excretion of 6-DMG, were evaluated following administration of single oral doses of an ultramicrosize and a microsize formulation of griseofulvin to 6 healthy volunteers. The bioavailability of griseofulvin was higher following the ultramicrosize formulation when 64% of the dose was recovered (via metabolites) versus 52% after the microsize preparation. Penetration into skin blister fluid was delayed as compared to plasma levels; the peak concentration in plasma was observed at 3–4 h, whereas griseofulvin in CBF increased up to 6 h. The terminal half-live was calculated from plasma levels to 9.3 h. The half-lives calculated from SBF and CBF concentrations were 9.2 and 9.8 h, respectively, (n=5). In plasma 84% of griseofulvin was bound to proteins, predominantly to albumin; binding in SBF and CBF was 72 and 82%, respectively. 3 h after drug administration the free concentration in plasma significantly exceeded the free concentrations in SBF and CBF. Distribution equilibrium between plasma and skin blister fluid was observed after 27 h. Thus, during chronic administration, the plasma griseofulvin level should reflect its concentration in the target organ.
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    Pharmacokinetics of theophylline and enprofylline in patients requiring a high or low dose of theophylline (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 115-117 
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    ISSN: 1432-1041
    Keywords: enprofylline ; theophylline ; pharmacokinetics ; patients ; theophylline requirement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In patients requiring a high or low dose of theophylline the pharmacokinetics of theophylline and enprofylline were studied. The low-dose group took an average daily dose of 8.91 mg/kg body wt. and the high-dose group 24.75 mg/kg body wt. The average half-life of theophylline in the former was 7.11 h and in the latter 4.72 h. The average clearances (CL) of theophylline were 2.83 and 4.58 l/h, respectively. The daily oral intake of theophylline was negatively correlated with the theophylline t1/2 (r=−0.63). While the t1/2 of enprofylline was similar in the two groups, CL and volume of distribution (Vc) were slightly (about 30%) but significantly higher in patients requiring a high dose of theophylline. CL of enprofylline did not correlate with CL of theophylline, nor was the Vc of the two drugs correlated. Interindividual variability in t1/2 and CL was considerably lower for enprofylline than for theophylline.
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    Pharmacokinetics of gentamicin in protein-energy malnutrition (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 255-256 
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    ISSN: 1432-1041
    Keywords: gentamicin ; malnutrition ; protein-energy deficiency ; malnourished children ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of i.m. gentamicin was the same in malnourished (n=6) and normal (n=4) children.
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    URL: http://dx.doi.org/10.1007/BF00547433
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    The effect of cimetidine on the pharmacokinetics, pharmacodynamics and alpha1-adrenoceptor responsiveness of trimazosin in man (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 301-306 
    Details
    ISSN: 1432-1041
    Keywords: trimazosin ; cimetidine ; pharmacokinetics ; alpha-adrenoceptor antagonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of cimetidine treatment on the pharmacokinetics and pharmacodynamics of single doses of trimazosin was studied in 6 normotensive volunteers. Co-administration of cimetidine did not significantly affect the overall magnitude of the hypotensive effect of trimazosin. However, the time profile of the blood pressure response was significantly modified particularly with attenuation of the delayed component. Co-administration of cimetidine did not alter alpha1-adrenoceptor antagonism by trimazosin. There was no significant change in the clearnace and volume of distribution of trimazosin but there was a significant reduction in the area under the concentration-time curve for the metabolite, 1-hydroxytrimazosin. The reduction in the AUC of 1-hydroxy-trimazosin corresponds in time with the attenuation of the delayed hypotensive response. This is consistent with the suggestion that the delayed hypotensive response is related to an active metabolite, probably 1-hydroxytrimazosin.
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    URL: http://dx.doi.org/10.1007/BF00544084
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    Pharmacokinetics of the loop diuretic piretanide in renal failure (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 337-343 
    Details
    ISSN: 1432-1041
    Keywords: piretanide ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Piretanide 60 mg was administered intravenously over 30 min to 15 men with different degrees of renal failure. The mean piretanide serum concentration at the end of the infusion period was 5.72±1.51 µg/ml. Serum piretanide concentration-time curves declined biexponentially and 24 hours after medication the serum level had fallen to less than twice the detection limit. The terminal half-life ranged from 1.63 to 3.44 h. A relationship to creatinine clearance was not demonstrable. The mean metabolic clearance of piretanide was 107.7±47.6 ml/min/1.73 m2 body surface area and was the same as that reported for healthy subjects. The renal clearance of piretanide ranged from 3.33 to 43.9 ml/min/1.73 m2 body surface area and very closely correlated with the creatinine clearance (p〈0.01). Its renal clearance dependend principally on active secretion of the drug into the tubule, and glomerular filtration appeared unimportant. There was a close relationship between the amount of piretanide excreted in the urine and the creatinine clearance. Because the diuretic effect of piretanide depends on the concentration of the drug in the tubule, the observed correlation might be of use in evaluating the appropriate dosage of piretanide in patients with renal failure. The present data suggest that single daily doses of piretanide will not result in accumulation, even when high doses are administered to patients with advanced renal failure.
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    URL: http://dx.doi.org/10.1007/BF00544091
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    Human plasma and skin blister fluid levels of griseofulvin after its repeated administration (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 351-354 
    Details
    ISSN: 1432-1041
    Keywords: griseofulvin ; skin blister fluid ; plasma concentration ; blister fluid concentration ; pharmacokinetics ; microsize formulation ; urinary excretion ; bioavailability ; different formulations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Griseofulvin was administered orally to 6 healthy volunteers for 6 days. The subjects received 500 mg of a microsize formulation and 330 mg of an ultramicrosize formulation, according to a cross-over design. The drug was determined in plasma, suction blister fluid (SBF) and cantharides blister fluid (CBF) following the last dose. Urinary excretion of the main metabolites 6-demethylgriseofulvin (6-DMG) and its glucuronic acid conjugate was also measured. The pharmacokinetic parameters were compared with those obtained from a recent single dose experiment. On repeated administration, the bioavailability of griseofulvin was significantly lower from the microsize formulation; the urinary recovery of total 6-DMG was 33.8% versus 53.6% on administration of the ultramicrosize material. Bioavailability was reduced as compared to ingestion of a single dose. The reduction was more prominent following the microsize (36%) than the ultramicrosize (17%) formulation. Penetration into skin blister fluid was not altered as compared to the single dose experiment. Relative areas under the blister fluid-time curves amounted to 51% (SBF) and 80% (CBF) of the area under the plasma level-time curve. The concentration of unbound griseofulvin in these body fluids was identical throughout the entire dosage interval. Unbound griseofulvin levels were low in comparison with the minimum inhibitory concentrations for strains of trichophyton and microsporum.
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    URL: http://dx.doi.org/10.1007/BF00544093
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    β-Adrenoceptor blocking effects and plasma levels of bornaprolol and propranolol in man (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 405-411 
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    ISSN: 1432-1041
    Keywords: bornaprolol ; propranolol ; beta-adrenoceptor blockade ; duration of action ; pharmacokinetics ; plasma renin activity ; bronchoconstriction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The β-adrenoceptor blocking effects and pharmacokinetics of bornaprolol (FM 24), a new β-adrenoceptor blocking agent, have been compared with those of propranolol and a placebo in a double-blind trial in 6 healthy volunteers. Heart rate, systolic and diastolic blood pressures and peak expiratory flow rate were measured at rest and at the end of 3 min vigorous exercise on a bicycle ergometer, before and 2, 24 and 48 h after single oral doses of bornaprolol (120, 240 and 480 mg) and propranolol (40, 80 and 160 mg). Plasma renin activity at rest and the plasma concentrations of the two drugs were determined. Bornaprolol significantly reduced resting heart rate, dose-dependently lowered exercise-induced tachycardia and decreased peak expiratory flow rate and plasma renin activity. In addition, exercise-induced tachycardia was significantly reduced by bornaprolol up to 48 hours after drug intake (pharmacodynamic half-life approximately 63–86 h) and there was a correlation between this reduction and the log plasma bornaprolol concentration over the 48-h period. Thus, bornaprolol behaved in man as a non-cardioselective and long-lasting β-adrenoceptor blocking drug, probably devoid of intrinsic sympathomimetic activity.
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    URL: http://dx.doi.org/10.1007/BF00613453
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  • 73
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    Intra-uterine pressure and serum ibuprofen: Observations after oral administration of 400 mg ibuprofen to a patient with primary dysmenorrhoea (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 443-446 
    Details
    ISSN: 1432-1041
    Keywords: dysmenorrhoea ; ibuprofen ; intra-uterine pressure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Intra-uterine pressure was recorded in a dysmenorrhoeic patient for 10 h before and after administration of a single dose of ibuprofen 400 mg. Bloodsamples were obtained at regular intervals during the recording for determination of the serum concentration of ibuprofen by reverse HPLC. The maximum serum concentration (37.4 µg Ml−1) was achieved after 1 h and the terminal half-life of ibuprofen was approximately 2 h. A marked reduction in intra-uterine pressure and the severity of pain was recorded 1.5 h following the administration of ibuprofen. Despite low or non-detectable serum concentrations of ibuprofen after 4 h, intra-uterine pressure never regained the level recorded before treatment.
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    URL: http://dx.doi.org/10.1007/BF00613459
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  • 74
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    Nasal bioavailability and systemic effects of the glucocorticoid budesonide in man (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 477-481 
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    ISSN: 1432-1041
    Keywords: budesonide ; glucocorticoid ; nasal administration ; pharmacokinetics ; bioavailability ; systemic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Budesonide, a topically potent glucocorticoid, was administered to 4 healthy volunteers by i.v. infusion and by nasal instillation of 100 µg tritium-labelled drug. Plasma was analyzed by liquid chromatography plus scintillation counting of collected fractions. After i.v. administration the plasma clearance was 0.92 l/min and the apparent volume of distribution was 2.8 l/kg. After nasal administration, the time to reach the peak plasma level was approximately 30 min, and the systemic availability was 102%. Budesonide had marginal effects on plasma cortisol and white blood cell counts either after i.v. or nasal administration. Thus, nasally instilled budesonide in solution is rapidly and completely absorbed from the nasal mucosa. The systemic effects after this clinically recommended nasal dose were negligible.
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    Comparison of renal excretion of pethidine (meperidine) and its metabolites in old and young patients (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 171-175 
    Details
    ISSN: 1432-1041
    Keywords: pethidine ; drug metabolism ; pethidine metabolites ; renal excretion ; pharmacokinetics ; geriatrics ; old age ; meperidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a previous study old subjects were found to eliminate pethidine and its active metabolite norpethidine more slowly than young people. To investigate whether this was due to the decline in renal function with age, the urinary output of pethidine and its metabolites pethidinic acid, norpethidine and norpethidinic acid was compared in old and young patients. The cumulative urinary excretion of pethidine and pethidinic acid over 24 h was similar in old and young patients. The slower elimination rate of pethidine from plasma might therefore be due to slower biotransformation of pethidine to norpethidine and norpethidinic acid. The cumulative urinary excretion of norpethidine and norpethidinic acid during 24 h was significantly lower in old patients than in young: 2.7% versus 7.1% (p〈0.001), and 5.5% versus 10.5% (p〈0.001). The renal clearance of norpethidine was inversely correlated with age. Thus, the slower disappearance of norpethidine from plasma in old patients is due to slower renal excretion of this metabolite. The renal clearance of pethidine showed pH-dependence and was usually smaller than the creatinine clearance. In contrast, renal clearance of norpethidine was correlated with creatinine clearance and was of the same magnitude. The difference in renal handling may be explained by the more polar character of norpethidine compared to its parent compound. The present study shows that not only the excretion of unchanged drugs may decline with increasing age but also that of drug metabolites, which may therefore reach higher plasma levels in old patients. If they are pharmacologically active they will increase and prolong the response to medication and possibly increase the risk of side effects.
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    URL: http://dx.doi.org/10.1007/BF00609687
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    Determination of thiamine in human plasma and its pharmacokinetics (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 213-219 
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    ISSN: 1432-1041
    Keywords: thiamine ; plasma level ; pharmacokinetics ; nonlinear renal elimination ; assay for clinical use
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A sensitive assay for thiamine suitable for clinical use has been developed. It is based on precolumn oxidation of thiamine to thiochrome followed by HPLC-separation and fluorescence detection. The assay is applicable to various biological materials, including human plasma. The minimum amount detectable was 5 fmol, minimum plasma concentration 0.5 nmol/l and minimum sample volume 0.3 ml plasma. Each chromatographic run took 3 min. Inter- and intra-assay relative standard deviations (RSD) were 8.3% and 6.3%, respectively, at a stock plasma concentration of 10.8 nmol/l. At 38.8 nmol/l, interassay RSD was reduced to 3.4%. The recovery of 5 nmol/l added thiamine was 102 (SD±17)%, that of 30 nmol/l was 94±5%. Plasma levels in 91 volunteers ranged from 6.6 to 43 nmol/l, showing a log normal distribution with a median of 11.6 nmol/l. Thiamine kinetics were studied in plasma and urine from 8 men after intravenous and oral doses of 50, 100 and 200 mg thiamine hydrochloride. In all individuals, nonlinear renal elimination kinetics were demonstrated by plotting the fractional amount of thiamine excreted unchanged in urine against the corresponding area under the plasma concentration — time curve.
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    Pharmacokinetic studies of cefoxitin in continuous ambulatory peritoneal dialysis (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 333-337 
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    ISSN: 1432-1041
    Keywords: cefotoxin ; renal failure ; peritoneal dialysis ; pharmacokinetics ; CAPD (continuous ambulatory dialysis) ; dialysate concentration ; intra peritoneal administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefoxitin was examined in 9 patients undergoing peritoneal dialysis for chronic renal failure. Cefoxitin was administered intraperitoneally in the dialysate fluid every 6 h for 24 h, in two different concentrations, 50 µg/ml and 100 µg/ml. The plasma half-life of cefoxitin was 20.2 h. The major route of elimination was non-renal, with a clearance of 8.0 ml/min. Peritoneal clearance was 4.1 ml/min. As expected, renal clearance was negligible. The peak plasma concentrations of cefoxitin at the two dose levels used were 7 µg/ml and 15 µg/ml, respectively, when assayed by HPLC, and 12 µg/ml and 24 µg/ml when determined by a microbiological assay. The cefoxitin concentration in the dialysate decreased from 50 µg/ml to 14 µg/ml and from 100µg/ml to 37 µg/ml during the 6 h of its retention in the peritoneal cavity.
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    Mechanism of warfarin potentiation by amiodarone: Dose — and concentration — Dependent inhibition of warfarin elimination (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 257-261 
    Details
    ISSN: 1432-1041
    Keywords: amiodarone ; warfarin ; drug interaction ; metabolism ; inhibition ; plasma concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Potentiation of the anticoagulant-effect of warfarin by amiodarone was studied in 30 patients. Thirteen received both drugs concurrently, and 17 received warfarin alone and the combination sequentially. Warfarin doses were adjusted to maintain the prothrombin time between 25–30% of control and its kinetics were compared to those in 20 control patients who received warfarin alone. Potentiation occurred in 28/30 patients, presenting as a 35%–65% reduction in the required dose of warfarin, and was correlated with the dose of amiodarone (r=0.77, p〈0.01). The free warfarin fraction was not affected by amiodarone (1.8% vs 1.6% in the controls). Warfarin clearance was lower in amiodarone-treated patients than in the controls (1.4 vs 3.1 ml/min, p〈0.01) with similar plasma concentrations (1.5 vs 1.2 µg/ml) despite administration of lower doses (23.3 vs 39 mg/week respectively). The amiodarone concentration was significantly correlated with the warfarin concentrations independent of the effect of amiodarone on the dose of warfarin. Amiodarone hat no effect on prothrombin other than through its actions on the dose and plasma concentration of warfarin. The mechanism of the amiodarone-warfarin interaction is pharmacokinetic through dose — and concentration — dependent inhibition of warfarin elimination.
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    Effect of oxidative polymorphism (debrisoquine/sparteine type) on hepatic first-pass metabolism of bufuralol (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 317-320 
    Details
    ISSN: 1432-1041
    Keywords: bufuralol ; debrisoquine ; sparteine ; genetic/oxidative polymorphism ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bufuralol is a beta-adrenoceptor blocking drug whose oxidative metabolism is under the same genetic control as debrisoquine and sparteine. The pharmacokinetics of bufuralol were studied in 10 healthy subjects (7 extensive and 3 poor metabolizers of debrisoquine) after oral and intravenous administration. In extensive metabolizers the systemic availability of bufuralol was 43%. Poor metabolizers were characterized by a considerable increase in systemic availability due to a corresponding decrease in hepatic first-pass metabolism. After oral administration of bufuralol non-linear kinetics may occur.
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    Pharmacokinetics of famotidine, a new H2-receptor antagonist, in relation to renal function (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 327-331 
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    ISSN: 1432-1041
    Keywords: famotidine ; renal failure ; H2-receptor antagonist ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new, potent H2-receptor antagonist, famotidine, 20 mg i.v. was studied in 7 subjects with normal renal function and in 24 patients with varying degrees of renal impairment. The volume of distribution at steady state was 1.14 l/kg in normal subjects and was not altered in renal failure. The half-life of elimination was 2.59 h in normal subjects and was unchanged in mild renal failure (creatinine clearance, CLCR 90–60 ml/min/1.48 m2) but was increased to 4.72 h in moderate renal failure (CLCR 60–30 ml/min/1.48 m2), and to 12.07 h in severe renal failure (CLCR below 30 ml/min/1.48 m2). The cumulative urinary excretion and renal clearance of famotidine were correspondingly reduced in patients with impaired kidney function. In normal subjects and in patients with mild to moderate renal failure, about 70% of famotidine was excreted through the kidney, mainly by tubular secretion. In patients with a CLCR above 60 ml/min/1.48 m2 the normal daily dose of famotidine can be employed, but in those with a CLCR between 60 and 30 ml/min/1.48 m2 the dose should be reduced by half, and in patients with a CLCR below 30 ml/min/1.48 m2 a reduction by three quarters of the normal dose is recommended.
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    Pharmacokinetics of verapamil in patients with renal failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 405-410 
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    ISSN: 1432-1041
    Keywords: verapamil ; renal failure ; norverapamil ; pharmacokinetics ; haemodialysis ; ECG ; blood pressure ; heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of verapamil was studied in patients with end-stage chronic renal failure and in normal subjects after i.v. injection of 3 mg and a single oral dose of 80 mg. Plasma levels of verapamil and its active metabolite norverapamil were measured by HPLC. After i.v. injection, the terminal phase half-life and total plasma clearance of verapamil in both groups were similar. Haemodialysis did not change the time course of plasma verapamil levels after i.v. administration. After a single oral dose, the plasma levels of verapamil and norverapamil in both groups of subjects were similar. Subsequently, normal volunteers and patients with renal failure were treated for 5 days with oral verapamil 80 mg t.d.s. There was no difference between the 2 groups of subjects in the trough and peak levels of verapamil or of norverapamil. Intravenous and oral administration of the calcium channel blocking agent had similar effects on blood pressure, heart rate and the PR-interval in the electrocardiogram in both groups. The study demonstrated that the disposition of verapamil was similar in normal subjects and in patients with renal failure.
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    Bioavailability and pharmacokinetics of ketanserin in elderly subjects (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 411-417 
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    ISSN: 1432-1041
    Keywords: ketanserin ; ketanserinol ; pharmacokinetics ; age ; healthy volunteers ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of ketanserin has been examined in a cross-over experiment in 21 elderly subjects (aged 59–72 years) by administration of tablets (40 mg), solution (40 mg) and injectable solution (10 mg). After two weeks of treatment with 40 mg ketanserin tablets further 18 blood samples for analysis were collected under steady-state conditions. Plasma levels were measured by HPLC. The absolute bioavailability of ketanserin tablets was 52.7%; their relative bioavailability compared to a solution containing an equal quantity of active compound was 85.5%. Therefore, the low absolute bioavailability of ketanserin cannot be attributed to the formulation. The active compound was rapidly liberated from the tablet, reaching a peak of 103.8 ng/ml after 0.97 h. Individual plasma level-time curves were fitted to an open three compartment model and a half-life of 17.7±7.26 h was calculated for the terminal elimination phase. An average terminal elimination half-life of 15.4±4.2 ng/ml was found after administration of the ketanserin solution. Multiple dosing with 40 mg tablets b.d.s. resulted in an AUC over one dosing interval at steady-state of 666±201 ng × h/ml. The AUC extrapolated to infinity was 1200±405 ng × h/ml for the last tablet. This is 1.8-times the AUC in one dosing interval, and 2.3-times the AUC of a single dose. Under steady-state conditions, the mean peak plasma level was 155.1 ng/ml (1.08 h after dosing) and the terminal half-life was 19.1±5.1 h. For the metabolite ketanserinol terminal half-lives of 21.4 h after a single tablet and 31.0 h after discontinuation of multiple dosing were calculated. Compared to the parent compound there was much more marked accumulation of ketanserinol. Despite moderate accumulation and prolongation of the terminal half-life of ketanserin under steady-state conditions, dosage adjustment is not required in elderly people. First-pass metabolism and bioavailability remained in the range found in previous studies of ketanserin in young subjects.
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    Intravenous and intramuscular pharmacokinetics of recombinant leukocyte a interferon (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 469-471 
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    ISSN: 1432-1041
    Keywords: interferon ; cancer patients ; recombinant leukocyte A interferon ; rIFN-αA ; i.v.-/i.m. administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Interferon is currently being evaluated for the treatment of disseminated cancer and viral diseases. Alpha interferons have shown to be effective in the treatment of a number of malignancies. Recombinant leukocyte A interferon (rIFN-αA) is an alpha interferon produced by recombinant DNA techniques. A kinetic evaluation of rIFN-αA following intravenous and intramuscular administration has not been adequately defined. The present study was designed to evaluate the kinetics of rIFN-αA following intravenous and intramuscular administration of 3, 9 or 18×106 units to patients with disseminated cancer. A preliminary report of this study was presented at the meeting of the American Society for Clinical Pharmacology and Therapeutics in San Diego, March 1983 (1).
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    Effect of impairment of renal function on the accumulation and disposition of isoxicam (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 585-588 
    Details
    ISSN: 1432-1041
    Keywords: isoxicam ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The accumulation and disposition of the non-steroidal antiinflammatory drug isoxicam were investigated following its oral administration to 6 subjects with normal renal function and 13 patients with diminished renal function. Isoxicam was given daily as a single oral dose for 14–15 consecutive days. Steady-state plasma levels were achieved after 13 days. The effect of differences in renal function on the kinetics of isoxicam appeared to be minimal. Accumulation of isoxicam was similar in both groups of subjects and there was no significant difference between the groups in the plasma clearance or terminal half-life of isoxicam. There were substantial differences between individuals in the apparent plasma clearance and half-life of the drug, and this is reflected in the 7-fold range of steady-state plasma isoxicam concentrations encountered in the subjects.
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    Pharmacokinetics of an extended-release dosage form of molsidomine in patients with coronary heart disease (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 611-613 
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    ISSN: 1432-1041
    Keywords: molsidomine ; angina pectoris ; pharmacokinetics ; molsidomine retard
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Molsidomine (N-carboxy-3-morpholino-sydnonimine-ethylester; Cassella-Riedel Pharma GmbH, Frankfurt/M. FRG) has an antianginal effect for up to 3–5 h after oral administration of 2 mg Corvaton [1]. Plasma levels of the parent drug can be measured during this interval. A new galenic formulation (Corvaton retard) has been developed to prolong the duration of the therapeutic action and to improve patient compliance. The present study was carried out to establish whether the in vitro dissolution profile of the tablet was reflected in vivo, thus permitting prediction of plasma molsidomine levels in patients with coronary heart disease.
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    Antisecretory effect and oral pharmacokinetics of omeprazole in patients with chronic renal failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 637-640 
    Details
    ISSN: 1432-1041
    Keywords: omeprazole ; renal failure ; gastric secretion ; pharmacokinetics ; haemodialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The inhibitory effect of omeprazole on gastric acid secretion was tested in a group of patients on haemodialysis for chronic renal failure. Single 30 mg doses almost totally inhibited basal acid output on both dialysis and non-dialysis days. Plateau acid output was reduced by a mean of 77% and 90% on non-dialysis and dialysis days respectively. The absorption and pharmacokinetic profile of omeprazole were not affected by dialysis. Omeprazole was not recoverable from dialysis fluid. It is concluded that omeprazole is a potent inhibitor of gastric acid secretion in patients with chronic renal failure, and its effect is not influenced by haemodialysis.
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    The influence of ascites on the pharmacokinetics of piretanide in cirrhotic patients (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 581-583 
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    ISSN: 1432-1041
    Keywords: piretanide ; liver cirrhosis ; ascites ; bioavailability ; pharmacokinetics ; diuretic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of piretanide, a new loop diuretic, were studied in seven patients with severe liver disease before and after resolution of ascites. The time to maximum concentration was significantly prolonged by the presence of ascites. Tmax after relief of ascites was similar to that seen for normal volunteers. Area under the curves, bioavailability, volumes of distribution and elimination half-lives did not change after resolution of the ascites: two patients in whom diuretic resistant ascites occurred showed similar pharmacokinetics to that of the diuretic responders. Reduced responsiveness to piretanide therapy in patients with gross ascites does not appear to be the result of decreased bioavailability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544070
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    Interactions between smectite, a mucus stabilizer, and acidic and basic drugs (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 601-605 
    Details
    ISSN: 1432-1041
    Keywords: smectite ; phenylbutazone ; diazepam ; pharmacokinetics ; drug interactions ; drug adsorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The interaction of phenylbutazone and diazepam with smectite were studied in in-vivo and in-vitro. The kinetics of both drugs were investigated in healthy subjects after oral administration as monotherapy or in association with smectite. Smectite did not substantially alter the kinetics of phenylbutazone, whereas the peak plasma concentration of diazepam was reduced to 91%, and the time of peak concentration was prolonged by 153% of the control values. The in-vitro investigations were conducted at pH 5.5 and 8 and showed that there was no interaction between phenylbutazone and smectite, but that it adsorbed diazepam. The findings suggest that smectite delays the absorption of basic drugs and does not alter the absorption kinetics of acidic drugs.
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    URL: http://dx.doi.org/10.1007/BF00544074
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  • 89
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    Factors affecting the kinetics of two benzothiazine non-steroidal anti-inflammatory medicines, piroxicam and isoxicam (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 689-692 
    Details
    ISSN: 1432-1041
    Keywords: isoxicam ; piroxicam ; pharmacokinetics ; elderly ; anti-inflammatory drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of isoxicam and piroxicam were compared in 12 young adults (〈40 years) and 12 elderly subjects (〉65 years). After a single oral dose of 200 mg isoxicam or 20 mg piroxicam blood samples were taken for 168 h and the plasma drug concentrations determined by HPLC. The elimination half life of piroxicam for the adults was 57.1±16.4 h (mean ± SD; harmonic mean 52.9 h) and for the elderly subjects was 57.8±22.1 h (harmonic mean 52.1 h). The corresponding values after isoxicam were 34.3±13.6 h (harmonic mean 31.6) for the adults and 39.1±22.7 h (harmonic mean 33.5) for the elderly subjects. Similarly no differences were noted in either the AUC0-∞ after piroxicam (adults 154.1±52.2 µg·h/ml, elderly 163.6±99.1 µg·h/ml) and isoxicam (adults 642.7±241.9 µg·h/ml, elderly 787.9±613.1 µg·h/ml) or the apparent oral clearance of piroxicam (adults 2.39±0.80 ml/min, elderly 2.51±0.90 ml/min) and isoxicam (adults 5.84±2.04 ml/min, elderly 5.59±2.12 ml/min). One adult and two elderly subjects exhibited slower elimination of both medicines than the remainder of each group. However determination of the oxidation phenotype using sparteine metabolism showed that this was not a likely determinant of the reduced clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607917
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  • 90
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    Disopyramide pharmacokinetics in patients with acute myocardial infarction (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 45-51 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; myocardial infarction ; antiarrhythmic agent ; pharmacokinetics ; protein binding ; intravenous administration ; oral administration ; gastro-intestinal absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To study the effects of acute myocardial infarction on the pharmacokinetics of disopyramide a single oral dose of disopyramide base (200 mg) was administered to 6 patients with myocardial infarction both in the acute (Study I) and recovery (Study II) phases. An intravenous tracer dose of14C-disopyramide (2.5 µg/0.3 mg) was given simultaneously with the oral dose. On the basis of the intravenous tracer data, the volume of distribution, binding to plasma proteins, total plasma clearance, renal clearance and elimination half-life of disopyramide and mono-N-dealkyl disopyramide were the same in Studies I and II. The peak serum concentrations of disopyramide after oral dosing in Studies I and II were 2.6±1.2 (SEM) and 6.4±1.9 µg/ml, respectively (p〈0.05), the peak times 3.29±1.22 and 1.21±0.39 h (N.S.) and the AUCINF 38.0±7.7 and 60.7±9.9 µg·h·ml−1 (p〈0.05). The recovery of disopyramide in urine over 3 days averaged 46% and 47% of dose, and that of mono-N-dealkyl disopyramide 22% and 16% of the dose, respectively. Thus, the gastrointestinal absorption of disopyramide was disturbed, resulting in low plasma concentrations after oral dosing, whereas the elimination of disopyramide was unaltered in the acute phase of myocardial infarction.
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    URL: http://dx.doi.org/10.1007/BF00635707
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  • 91
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    Polymorphic metabolism of the β-adrenoreceptor blocking drugs and its clinical relevance (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 77-84 
    Details
    ISSN: 1432-1041
    Keywords: β-Blockers ; debrisoquine metabolism ; extensive metabolizers ; genetic polymorphism ; poor metabolizers ; glucuronidation ; lipophilicity ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Although β-Blockers are structurally closely related, there are marked differences in the extent of metabolism, related mainly to relative lipophilicity. Lipophilic β-Blockers are metabolized by C-oxidative pathways and glucuronidation. Metabolism of lipophilic β-Blockers is important in determining pharmacokinetics, formation of active metabolites, stereoselectivity and isomer preference, and interphenotypic variation. The oxidative clearance of metoprolol, timolol and bufuralol is regulated/influenced by the debrisoquine hydroxylation gene locus. The metabolism of these lipophilic β-Blockers thus exhibits polymorphic characteristics, there being significant interphenotype differences in pharmacokinetics (bioavailability, peak plasma level, plasma terminal t1/2) between the poor and extensive metabolizers of debrisoquine. There are similar interphenotype differences in β-blocker pharmacodynamics in terms of β-blockade. A number of adverse effects of lipophilic β-Blockers have been hypothesized to predominate in the poor metabolizer phenotype including unacceptable bradycardia, loss of cardioselectivity, greater CNS side-effects, and interactions with drugs metabolized by the same polymorphic systems. However, objective evidence for this is lacking.
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    URL: http://dx.doi.org/10.1007/BF00543715
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  • 92
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    Atenolol inhibits the elimination of disopyramide (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 41-43 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; atenolol ; pharmacokinetics ; drug interaction ; ischaemic heart disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of atenolol on the total elimination of disopyramide and its main dealkylated metabolite was studied in 6 patients and 3 volunteers. During administration of 50 mg atenolol b.i.d. the clearance of disopyramide decreased significantly (p〈0.02) from 1.90±0.71 (X±SD) to 1.59±0.68 ml/kg/min, while its half-life, concentration of the metabolite, and the volume of distribution remained unchanged. The reduction in the clearance of disopyramide by atenolol might contribute to the alleged pharmacodynamic interaction between disopyramide and β-blocking drugs.
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    URL: http://dx.doi.org/10.1007/BF00635706
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  • 93
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    Pharmacokinetics and pharmacodynamics of procyclidine in man (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 73-78 
    Details
    ISSN: 1432-1041
    Keywords: procyclidine ; Kemadrin ; pharmacokinetics ; pharmacodynamics ; humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics of procyclidine (10 mg) after oral and intravenous administration were studied in six healthy volunteers. Treatment order was randomised and the study was placebo-controlled and conducted blind. After oral dosing the mean peak plasma concentration was 116 ng/ml and mean bioavailability was 75%. After both oral and intravenous dosing the mean values for the volume of distribution, total body clearance and plasma elimination half-life of procyclidine were in the order of 1 l/kg, 68 ml/min and 12 h respectively. Autonomic effects were maximal within 0.5 h of intravenous administration and at about 1–2 h after oral dosing. Significant effects on pupil diameter, visual near point, salivary secretion and heart rate occurred after intravenous treatment and similar but less marked effects occurred after the oral dose. Significant autonomic effects were still detectable 12 h after both forms of treatment.
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    URL: http://dx.doi.org/10.1007/BF00635711
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  • 94
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    Deconvolution applied to the kinetics of extracorporal drug removal. Haemodialysis of cefsulodin (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 503-509 
    Details
    ISSN: 1432-1041
    Keywords: deconvolution ; haemodialysis ; cefsulodin ; extracorporal drug removal ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A novel approach to the evaluation of the kinetics of drug removal by an extracorporal device (ECD), e.g., haemodialysis, haemofiltration, and haemoperfusion, is presented. The rate and extent of extracorporal drug removal (ECR) are determined by deconvolution. The proposed method is model independent in the sense that no specific models of corporal or extracorporal disposition are required. The estimation of various derived functions and parameters useful for describing ECR such as clearance and fractional drug removal are facilitated by the technique. The kinetics of cefsulodin elimination by haemodialysis in 3 patients were evaluated using the deconvolution approach. The results indicated that cefsulodin was dialyzable with ∼50% of the drug in the body removed by haemodialysis over 3–4 h.
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    URL: http://dx.doi.org/10.1007/BF00613469
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  • 95
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    Identification of sex pheromone components of jack pine budworm,Choristoneura pinus pinus freeman (1985)
    Springer
    Journal of chemical ecology 11 (1985), S. 159-167 
    Details
    ISSN: 1573-1561
    Keywords: Choristoneura pinus pinus ; jack pine budworm ; Lepidoptera ; Tortricidae ; (E,Z)-11-tetradecenyl acetate ; (E,Z)-11-tetradecen-1-ol ; sex pheromone ; sex attractant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Chemical identification and field-trapping experiments have shown that a blend of 85∶15 (E,Z)-11-tetradecenyl acetates and 85∶15 (E,Z)-11-tetradecen-1-ols (in a 9∶1 ratio) are female sex pheromone components for jack pine budworm,Choristoneura pinus pinus. This blend of chemicals, formulated in PVC (0.1 %, w/w) sources is as effective a trap bait as virgin females. Preliminary wind tunnel observations have indicated that this blend, effective as a trap bait, is not equivalent to females.
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    URL: http://dx.doi.org/10.1007/BF00988198
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  • 96
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    Oviposition and feeding preferences of the southern pine coneworm (Lepidoptera: Pyralidae) for different host-plant materials and observations on monoterpenes as an oviposition stimulant (1985)
    Springer
    Journal of chemical ecology 11 (1985), S. 689-699 
    Details
    ISSN: 1573-1561
    Keywords: Southern pine coneworm ; Dioryctria amatella (Hulst) ; Lepidoptera ; Pyralidae ; oviposition and feeding preference ; synthetic oviposition stimulant ; slash pine ; Pinus elliottii Engelm. var.elliottii ; monoterpenes ; fusiform rust ; Cronartium quercuum (Berk.) Miy. ex Shirai f. sp.fusiforme
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Bioassays were conducted with first-stage larvae and newly emerged females of the southern pine coneworm,Dioryctria amatella (Hulst), to detect feeding and ovipositional preferences for different host-plant materials collected between April and August. Correlations between measures of insect preferences and estimates of wood parameters indicated that larvae preferred to feed on host-plant materials with high moisture contents, low wood densities, and low monoterpene contents. Female moths, however, did not necessarily select those plant materials preferred by larvae for feeding, but tended to oviposit more frequently on materials with high monoterpene contents. A synthetic mixture of monoterpenes similar in composition to those present in fusiform rust galls of slash pine (Pinus elliottii) Englem. var.elliottii) elicited mating and oviposition behavior.
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    URL: http://dx.doi.org/10.1007/BF00988298
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  • 97
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    Kairomones for the egg parasiteTrichogramma evanescens Westwood (1985)
    Springer
    Journal of chemical ecology 11 (1985), S. 793-800 
    Details
    ISSN: 1573-1561
    Keywords: Trichogramma evanescens ; Hymenoptera ; Trichogrammatidae ; Pieris brassicae ; Pieris rapae ; Lepidoptera ; Pieridae ; kairomone ; oviposition ; deterring pheromone ; accessory gland ; egg parasite ; tricosane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract In observation-cage experiments some new contact kairomones for the egg parasiteTrichogramma evanescens Westwood are demonstrated.T. evanescens females search significantly longer on cabbage leaves treated with the wing scales of two hosts,Pieris brassicae L. andP. rapae L. Further, egg washes ofP. brassicae containing an oviposition deterrent pheromone for the butterflies, were found to have a contact-kairomonal effect on the parasite.T. evanescens females search significantly longer on cabbage leaves sprayed with a methanol or water wash ofP. brassicae eggs than on leaves treated with the solvent only.
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    URL: http://dx.doi.org/10.1007/BF00988306
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    Double-bond location in monounsaturated fatty acids by dimethyl disulfide derivatization and mass spectrometry: Application to analysis of fatty acids in pheromone glands of four lepidoptera (1985)
    Springer
    Journal of chemical ecology 11 (1985), S. 265-277 
    Details
    ISSN: 1573-1561
    Keywords: Fatty acid analysis ; double-bond location ; dimethyl disulfide adducts ; mass spectrometry ; pheromone ; Choristoneura fumiferana ; C. occidentalis ; C. pinus pinus ; Plusia chalcites ; Lepidoptera ; Tortricidae ; Noctuidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract A rapid analytical procedure for the determination of the position of double bonds in mixtures of monounsaturated fatty acid methyl esters has been developed. The method is based on direct capillary GC-MS-EI analysis of dimethyl disulfide adducts. The procedure was applied to mixtures of monounsaturated fatty esters from pheromone gland extracts of three tortricids from theChoristoneura genus,C. fumiferana, C. occidentalis, andC. pinus pinus, and one noctuid from the Plusiinae subfamily,Plusia chalcites. A correlation was found between the known major pheromone components in the four species with the corresponding fatty acids. Some of the additional fatty acids may be precursors to as yet unidentified minor pheromone components, present in extremely small quantities, in these species.
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    URL: http://dx.doi.org/10.1007/BF01411414
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  • 99
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    Intracellular pathways of receptor-bound GnRH agonist in pituitary gonadotropes (1985)
    Springer
    Cell & tissue research 239 (1985), S. 3-8 
    Details
    ISSN: 1432-0878
    Keywords: GnRH receptors ; Gonadotropes ; Coated pits ; Internalization ; High-resolution autoradiography ; LHRH, Gonadoliberin ; Pituitary gland ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Localization of GnRH receptors in rat pituitary gonadotropes was studied by use of 125I-[azidobenzoyl-D-Lys6]GnRH which, upon photolysis, is covalently bound to the receptor molecule. Using high resolution autoradiography, it was found that, after a 90-min incubation of the analog with pituitary cells at 4° C, 93% of the silver grains were associated with the plasma membrane of the gonadotropes. After 45-min incubation of the cells at 37° C, clustering and internalization of the receptor-bound GnRH analog were evident. Silver grains were associated with coated pits, intracellular vesicles, Golgi complexes, lysosome-like structures and secretory granules. The data indicate that receptor-bound GnRH agonist is internalized, at least in part, via coated pits and is subsequently routed to lysosomes where degradation of the hormone-receptor complex may occur. The presence of a considerable amount of silver grains associated with secretory granules may suggest that some of the internalized receptor molecules can escape degradation and be recycled to the cell membrane.
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    URL: http://dx.doi.org/10.1007/BF00214895
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  • 100
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    Distribution pattern of drained antigens and antibodies in the subcapsular sinus of the lymph node of the rat (1985)
    Springer
    Cell & tissue research 239 (1985), S. 31-35 
    Details
    ISSN: 1432-0878
    Keywords: Lymph filtration ; Antigen and antibody distribution ; Subcapsular sinus ; Lymph node ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A recent study of lymph nodes of the rat showed that they are morphologically and physiologically compartmentalized. A compartment of a node includes a portion of subcapsular sinus into which the lymph, entering via the related afferent lymphatic opening, is filtered. The study also showed that colloidal carbon injected locally in a small dose becomes predominantly associated with the areas of the inner wall of the subcapsular sinus that cover the extrafollicular zone of the peripheral cortex. Little carbon is seen over the folliculo-nodules (follicles with a nodule or germinal center). The question arose as to whether drained natural substances, as antigens and antibodies, follow the same pattern of distribution in the subcapsular sinus as the carbon. Therefore, small doses of fluorescein isothyocyanate (FITC)-conjugated antigens were injected locally into normal rats whose own antibodies in the nodes were stained by immunofluorescence. The pattern of distribution of the antigens in the draining nodes was found to be the same as that of the carbon. Furthermore, the lymph-carried antibodies of the rats were found to follow the same pattern. The morphological basis for such a pattern is explained. The results are further discussed with regard to the probable normal entry route of lymph-carried antigens in the parenchyma of nodes.
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    URL: http://dx.doi.org/10.1007/BF00214899
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