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  • 1
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    Springer
    Entomologia experimentalis et applicata 80 (1996), S. 145-148 
    ISSN: 1570-7458
    Keywords: fruit-piercing moths ; Pacific biotypes ; Lepidoptera ; Noctuidae ; Fabaceae ; Menispermaceae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 2
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    Entomologia experimentalis et applicata 80 (1996), S. 149-151 
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Satyridae ; wing pattern induction ; food plant quality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 3
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    Entomologia experimentalis et applicata 80 (1996), S. 152-155 
    ISSN: 1570-7458
    Keywords: predispersal seed predator guild ; Leguminosae ; Bruchidae ; Curculionidae ; Lepidoptera ; intra-and interspecific competition ; Monte Carlo simulation
    Source: Springer Online Journal Archives 1860-2000
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  • 4
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    Entomologia experimentalis et applicata 86 (1998), S. 89-96 
    ISSN: 1570-7458
    Keywords: spruce budworm ; amino acids ; chemosensilla ; electrophysiology ; gustation ; Lepidoptera ; Tortricidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract An electrophysiological approach was used to record the responses of maxillary styloconic sensilla of fourth- and sixth-instar larvae of the spruce budworm Choristoneura fumiferana to 14 amino acids. One cell in the lateral styloconic sensillum was identified as an amino acid-sensitive neuron. All of the amino acids tested, except l-proline and l-arginine, were detected by this cell. Arginine did not evoke a response from either the medial or lateral styloconic sensilla. Proline evoked responses from a cell in the medial styloconic sensillum. It is known from previous behavioural work that l-proline is a phagostimulant and l-valine inhibits feeding in Choristoneura; we thus further characterized the responses to these two amino acids. For both instars, l-proline was detected as low as 0.001 mmol/l and the maximal response was at 50 mmol/l. Stimulation of fourth- and sixth-instar larvae with l-valine showed that the maximum firing frequency was obtained at 1 mmol/l. Above and below this concentration, firing frequency decreases. Sensory responses to the amino acids stimuli did not correlate with known behavioral responses to similar stimuli.
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  • 5
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    Entomologia experimentalis et applicata 86 (1998), S. 331-336 
    ISSN: 1570-7458
    Keywords: adult diet ; fecundity ; larval phase ; Lepidoptera ; Noctuidae ; Spodoptera exempta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 6
    ISSN: 1570-7458
    Keywords: attraction ; Allium ; EAG ; generations ; green leaf volatiles ; Hyponomeutoidea ; Lepidoptera ; leek moth ; walking behaviour ; olfactory responsiveness ; rearing conditions ; sensitivity variations ; sulphur volatiles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Three strains of the leek moth, Acrolepiopsis assectella, were compared: two reared on leek leaves (Allium porrum) for which generations 10 to 12 (L) or generation 2 (G2) were used, the third one (D) reared on an artificial diet incorporating leek powder, for which generation ca 140 was examined. The walking behaviour (L and D) and the antennal responsiveness (L, G2 and D) were compared between individuals subjected to leek leaf odour and 4 volatiles identified in these leaves: 2 specific sulphur ones (dipropyl thiosulphinate and dipropyl disulphide) and 2 ‘general green leaf volatiles’ (cis-3-hexen-1-ol and trans-2-hexen-1-ol). The walking behavioural thresholds to leek odour, dipropyl thiosulphinate, and cis-3-hexen-1-ol were lower for L than for D females. The chemoanemotactic responses to dipropyl disulphide are almost identical, and trans-2-hexen-1-ol has nearly no activity. Accordingly, the olfactory sensitivity (assessed by EAG) to sulphur volatiles and cis-3-hexen-1-ol was higher for L and G2 females than for D ones. The threshold for thiosulphinate was at a concentration (v/v) of 4 × 10-4 M/l for D females, 4 × 10-5 M/l for L females and 4 × 10-8 M/l for G2 ones. It may be hypothesised that laboratory rearing conditions cause variations in the thresholds of antennal sensitivity and walking behaviour to specific and more efficient leek volatiles. This may result from the selective pressures experienced by the larvae reared in the laboratory.
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  • 7
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    Entomologia experimentalis et applicata 79 (1996), S. 51-59 
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Tortricidae ; mating disruption ; pest control ; multiple sources ; attraction ; arrestment ; interruption ; range ; (Z)-8-dodecenyl acetate ; (E)-8-dodecenyl acetate ; (Z)-8-dodecanol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The behaviour of Grapholita molesta (Busck) (Lepidoptera: Tortricidae) males was studied in overlapping sex pheromone plumes in a wind tunnel. The ultimate aim of the study was to assess the effect of different treatments on male behaviour and consider the observed changes within the context of the suggested mechanisms underlying mating disruption. Two baits were placed either in series or parallel using both synthetic pheromone blends and female extracts. One bait, the reference containing (Z)-8-dodecenyl acetate/(E)-8-dodecenyl acetate/(Z)-8-dodecenol in a ratio of 100/6/10 was kept constant at a dose of 100 μg of the main component, giving a composition and a release rate close to that of a female. The dose of the other bait varied between 0.1 and 100 times the concentration of the reference and was a mixture of one, two or three pheromone components. Males clearly discriminated between different blends and doses in the overlapping plumes, for regardless if the lures were presented in series or in parallel they followed the complete plume. Complete suppression of the response to the reference was only achieved with 300 μg of the optimal three-component blend on the other lure. When tested singly, a bait consisting of Z8-12:OAc/E8-12:OAc/Z8-12:O Hin a 100/0.2/0.4 ratio, attracted a high proportion of the males when placed 75 cm upwind of the male release site, but no males from 150 cm. Our data suggest that complete pheromone blends should be more effective than any incomplete blends in mating disruption formulations for G. molesta.
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  • 8
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    Entomologia experimentalis et applicata 79 (1996), S. 195-202 
    ISSN: 1570-7458
    Keywords: antifeedant ; drimane ; feeding behaviour ; sensory response ; structure-activity relationship ; neural code ; Pieris brassicae ; Lepidoptera ; Pieridae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Fifteen drimane compounds were tested for their feeding inhibiting activity in larvae of Pieris brassicae L. (Lepidoptera: Pieridae) when applied to leaf material of the host plant Brassica oleracea L. The antifeedant efficacy of the drimanes was related to their molecular structure in order to identify important functional groups. Of the drimanes tested, those with a lactone group on the B-ring were the most effective feeding inhibitors. Additionally, the sensory responses to 13 of the drimanes were measured. Neural activity was evoked in the deterrent cell in the medial sensillum styloconicum. Also, inhibition of sensory responses to feeding stimulants was found. Results of behavioural and electrophysiological tests were correlated in an attempt to elucidate the sensory code underlying feeding inhibition by drimanes in Pieris brassicae. It was concluded that the response of the deterrent cell in the medial sensillum styloconicum contributes significantly to inhibition of feeding behaviour in larvae of Pieris brassicae.
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  • 9
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    Entomologia experimentalis et applicata 79 (1996), S. 227-234 
    ISSN: 1570-7458
    Keywords: Helicoverpa zea ; Lepidoptera ; Noctuidae ; Eucelatoria bryani ; Eucelatoria rubentis ; Diptera ; Tachinidae ; parasitoid competition ; host discrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Multiple parasitism of Helicoverpa zea (Lepidoptera: Noctuidae) had differential effects on the gregarious endoparasitoids Eucelatoria bryani and E. rubentis (Diptera: Tachinidae). Both species were able to survive in multiparasitized hosts. However while the survival of E. bryani was not affected by the presence of E. rubentis, E. rubentis survival was reduced when competing with 24-h older E. bryani. The presence of E. rubentis did not result in a decrease in the size of E. bryani except when E. rubentis was 24-h older than E. bryani. The presence of E. bryani tended to result in smaller E. rubentis. The presence of similarly aged heterospecific competitors often resulted in prolonged development time for both species. Naïve females did not alter oviposition between unparasitized and heterospecifically parasitized fifth-instar larvae of H. zea, either by ovipositing less frequently in parasitized hosts than unparasitized ones, or by reducing clutch size in parasitized hosts. These results indicate that in H. zea, E. bryani is a superior competitor compared with E. rubentis. These factors should be considered in evaluating the potential of E. bryani and E. rubentis as biological control agents of H. zea.
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  • 10
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    Entomologia experimentalis et applicata 86 (1998), S. 313-318 
    ISSN: 1570-7458
    Keywords: Ostrinia palustralis ; sex pheromone ; identification ; (E)-11-tetradecenyl acetate ; (Z)-11-tetradecenyl acetate ; Lepidoptera ; Pyralidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract By means of gas chromatography with electroantennographic detection, gas chromatography-mass spectrometry and a series of bioassays, (E)-11-tetradecenyl acetate (E11-14:OAc) and (Z)-11-tetradecenyl acetate (Z11-14:OAc) at a ratio of 99:1 were identified as female sex pheromone components of Ostrinia palustralis. The average amounts of E11- 14:OAc and Z11-14:OAc in a single sex pheromone gland were 37.2±24.4 ng and 0.3±0.2 ng, respectively. In a wind-tunnel bioassay, the binary blend of E11- and Z11-14:OAc elicited the same male behavioral responses as did virgin females.
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  • 11
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    Entomologia experimentalis et applicata 88 (1998), S. 1-7 
    ISSN: 1570-7458
    Keywords: Lobesia botrana ; Lepidoptera ; Tortricidae ; fungus ; Botrytis cinerea ; attraction ; olfaction ; gustation ; olfactometer ; larval behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In vineyards, larvae of Lobesia botrana (Denis and Schiffermüller) (Lepidoptera: Tortricidae) and Botrytis cinerea (Persoon: Fries) often occur together. This study was carried out to establish whether first instar larvae are attracted by the fungus. Olfactory and gustatory responses of larvae to the fungus were investigated on grape berry clusters (Vitis vinifera) and in two types of olfactometer. In clusters infected partly by B. cinerea, 82% of first instar larvae settled where berries had been infected. In the olfactometers, first instar larvae detected and discriminated between two tested foods. They significantly preferred synthetic media or grape berries (cv., 'Alphonse Lavallée' or 'Cabernet Sauvignon') infected with B. cinerea to non-infected controls. The olfactory response led to 62.2% to 72.6% of the first instar larvae attracted by the fungus and the association of olfactory with gustatory responses resulted in similar rates (64.1% to 81.6%). So, the larvae were most attracted by synthetic media or grape berries infected by the fungus as compared to the controls. Olfaction appears to be the main sense involved in this attraction process.
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  • 12
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Gelechiidae ; Pectinophora gossypiella ; cotton ; pheromone ; wind tunnel ; attraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The mechanisms by which the application of formulated pheromone interferes with mating in the pink bollworm moth (PBW), Pectinophora gossypiella were examined in 0.4 ha cotton fields using high-dose (78 mg A.I.) sealed polyethylene dispensers. Walk-in, field wind tunnels 6.2 m long were placed over two rows of cotton. Treatments consisted of a control, a tunnel in a field free of disruptant formulation; a 3-rope treatment, in which the field was free of pheromone but one of the cotton rows in the wind tunnel was treated with 3 PBW ropes; and a rope-grid treatment, in which the field was treated with PBW ropes at the standard density of 1000 ha−1 and one of the cotton rows inside the wind tunnel was treated with 3 PBW ropes. We released marked males into the tunnels near sunset or held them in field cages for 24 h prior to assay. Two pheromone traps at the tunnel's upwind end monitored the ability of males to locate point sources of pheromone. In the 3-rope tunnel, traps placed upwind of the cotton row treated with disruptant pheromone captured far fewer males than those placed upwind of the untreated cotton row. In the tunnel situated in the centre of the rope-gridded field, very few males were caught in traps in both rows, indicating a camouflage of the pheromone plumes from the traps by the background of airborne disruptant drawn into the tunnel from the field. Activity of moths near the synthetic pheromone sources was video-recorded. Males oriented to, landed on or near, and walked on or near, PBW ropes, indicating competition between pheromone sources as a mechanism of mating disruption. Most males visiting PBW ropes became quiescent or disappeared from the field of view after a few minutes, suggesting a habituation/adaptation of response. The rhythm of attraction of males held in the field for 24 h before release was comprised of a small peak of activity near 2000 h, with the majority of attraction between 2300 and 0300 h. Much of the attraction before 0100 appears to be an advancement of the male's normal diel rhythm, caused by the presence of disruptant. Together these findings indicate that mating disruption of pink bollworm using the PBW ropes is achieved by a combination of mechanisms: a camouflage of natural plumes, competition between pheromone sources, habituation, and some advancement of the male's rhythm of response.
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  • 13
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    Entomologia experimentalis et applicata 80 (1996), S. 15-18 
    ISSN: 1570-7458
    Keywords: pheromone-binding protein ; general odorant-binding protein ; sensillum trichodeum ; sensillum basiconicum ; Lepidoptera ; immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 14
    ISSN: 1570-7458
    Keywords: insect ; parasitoid ; protein ; free amino acid ; cadmiun ; lead ; copper ; zinc ; Lepidoptera ; Hymenoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Heavy metal contamination of the forest pest insect Lymantria dispar (L.) (Lepidoptera; Lymantriidae), the gypsy moth, can alter its haemolymph composition, as has already been shown for carbohydrates and lipids in recent studies. L. dispar larvae are frequently parasitized by Glyptapanteles liparidis (Bouché) (Hymenoptera; Braconidae) larvae, which can—to some extent—regulate the population size of the pest insect. The parasitoids feed on the haemolymph of L. dispar larvae; hence, a different haemolymph composition of the host alters the trophic situation of the parasitoids. The aim of the present study was to investigate whether metal contamination also affects the concentrations of free amino acids in L. dispar haemolymph, and protein concentrations in their haemolymph and tissue. L. dispar larvae were parasitized on the first day of the second instar and then reared on diets contaminated with Cd, Pb, Cu or Zn at two concentrations each. Haemolymph and total body tissue of the larvae (fourth instar/third day) were analyzed. The concentrations of the free amino acids were elevated in five out of the eight contamination groups (Cd6, Pb4, Cu6, Cu10, Zn60), whereas haemolymph protein concentrations were significantly reduced in all contaminated individuals. The haemolymph protein concentration was 18 mg/ml in the control group and decreased to less than 10 mg/ml due to cadmium and zinc contamination at both concentrations and in the low copper contamination group. In contrast, total body proteins (136 μg/mg dry weight in the control group) were elevated due to heavy metal stress. Analyses of haemolymph protein concentrations during the fourth instar demonstrated an increase of the proteins from day one to day four (followed by a decrease on the fifth day) in the control group and the cadmium contamination group. A steady increase of proteins from the first to the fifth day in the copper and zinc contaminated larvae indicated a retarded development in these groups. Thus, the present study along with other recent studies demonstrated, that heavy metal stress changes the concentrations of all main haemolymph compounds of L. dispar larvae.
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  • 15
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    Entomologia experimentalis et applicata 81 (1996), S. 307-313 
    ISSN: 1570-7458
    Keywords: feeding deterrents ; desensitization ; habituation ; azadirachtin ; neem ; Spodoptera litura ; Lepidoptera ; Noctuidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The deterrence of azadirachtin, in its pure form and as a constituent of neem seed extract, to fifth instar Spodoptera litura (Fab.) larvae, was measured using cabbage, Brassica oleraceae (L.) var. capitata, leaf disc assays. Paired-choice assays, in which larvae could choose between feeding on a treated (1.3 ng azadirachtin per square cm leaf area) or an untreated leaf disc for 2 h, were conducted at 24 h intervals throughout the fifth instar. In addition, no-choice assays, in which larvae could feed on only one leaf disc (10 ng azadirachtin per square cm leaf area) for 1.5 h, were conducted consecutively over a six hour period at the beginning of the fifth instar. The effects of hunger and habituation on desensitization in our no-choice tests were partitioned. After repeated exposures, larvae became desensitized to pure azadirachtinal in both choice and no-choice tests, but did not desensitize to neem containing the same absolute amount of azadirachtin in choice tests. Hunger was responsible for approximately one third of the desensitization response in the no-choice tests. Sensitivity to azadirachtin was independent of age within the fifth instar.
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  • 16
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    Entomologia experimentalis et applicata 87 (1998), S. 209-209 
    ISSN: 1570-7458
    Keywords: Chrysodeixis chalcites ; EAG ; electroantennography ; electrophysiology ; greenhouse cultures ; Lepidoptera ; mating disruption ; Noctuidae ; paprika ; pheromone distribution ; sex pheromones ; sweet pepper
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Mating disruption using pheromone dispensers is an emerging insect control method in greenhouses in the Netherlands. For routine measurements of the pheromone level in greenhouses a portable and compact device based on electroantennography (EAG) was developed. The instrument was tested in different greenhouses under varying conditions using antennae of males of the noctuid moth Chrysodeixis chalcites. Relative differences in pheromone concentration between greenhouses loaded with pheromone dispensers and control greenhouses could be measured in a reliable way. Changes in pheromone concentration were clearly demonstrated by measurements during the growing season. The advantages of the instrument presented over previously described devices are its true portableness, ease of use and uncomplicated measuring principle. The device can be operated routinely by non-experts, and many measurements can be made in a short period of time. Preliminary outdoor measurements using antennae of male Cydia pomonella as sensor showed the potential of the instrument for use in the open field. The portable EAG sensor described here may provide a practical means for monitoring pheromone concentration and dispersal from dispensers applied for mating disruption.
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  • 17
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    Entomologia experimentalis et applicata 78 (1996), S. 1-8 
    ISSN: 1570-7458
    Keywords: induction ; imprinting ; learning ; caterpillar ; Lepidoptera ; experience ; diet breadth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract This review discusses the ambiguity of results obtained from dual-choice feeding tests, especially in relation to the study of effects of experience. Induced preference experiments done this way can be caused by up to nine potential changes in caterpillar behavior. In addition different physiological mechanisms that could lead to the process of induced preference are discussed. These include habituation to deterrents, the increased ability to process xenobiotics, the acquisition of specific positive responses, sensitization, and associative learning. These different processes might relate to function in different ways so that distinguishing them is important to progress in understanding the phenomenon. Suggestions for experimental designs that provide details on processes involved are indicated.
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  • 18
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    Entomologia experimentalis et applicata 80 (1996), S. 120-123 
    ISSN: 1570-7458
    Keywords: electroantennography ; Lepidoptera ; plant odours ; Ostrinia nubilalis
    Source: Springer Online Journal Archives 1860-2000
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  • 19
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    Entomologia experimentalis et applicata 80 (1996), S. 289-292 
    ISSN: 1570-7458
    Keywords: tri-trophic interactions ; demography ; diamondback moth ; Plutella xylostella ; Lepidoptera ; Plutellidae ; Diadegma insulare ; Hymenoptera ; Ichneumonidae ; cabbage looper ; Trichoplusia ; Noctuidae ; Patrocloides montanus ; Cruciferae ; Brassica oleracea ; B. nigra ; fertilization ; sex ratio
    Source: Springer Online Journal Archives 1860-2000
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  • 20
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    Entomologia experimentalis et applicata 80 (1996), S. 315-319 
    ISSN: 1570-7458
    Keywords: phylogeny ; host shift ; climate ; abiotic thermal constraints ; leaf quality ; phenology ; larval growth ; oviposition preference ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
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  • 21
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    Entomologia experimentalis et applicata 81 (1996), S. 315-323 
    ISSN: 1570-7458
    Keywords: disruption ; pheromone ; mass trapping ; Pectinophora gossypiella ; Lepidoptera ; cotton ; Brazil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Mass Trapping was used to control pink bollworm (PBW), Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae), populations in cotton fields in Brazil. Oil traps containing lures with a high dose of pheromone, installed at a density of 20 traps per ha soon after the occurrence of the first cotton fruits (or bolls), suppressed PBW populations below detection levels using Delta traps and manual examination of 100 green cotton bolls per ha. Pheromone sources of 0,2 g (approximately 150 NoMate® fibers) were effective in attracting PBW male moths to oil traps for at least three weeks. Trap captures showed that PBW males located the high concentration pheromone plumes, oriented upwind, and landed on or inside the traps. The long life of the pheromone sources and the long lasting viscosity of the oil surface ensured low trap maintenance, thus rendering mass trapping viable as an alternative technique for the control of P. gossypiella populations in commercial cotton fields. We discuss probable mechanisms promoting suppression of PBW populations in fields with mass trapping control.
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  • 22
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    Entomologia experimentalis et applicata 88 (1998), S. 101-107 
    ISSN: 1570-7458
    Keywords: sex pheromone ; pheromone-based mating disruption ; Spilonota ocellana ; Lepidoptera ; Tortricidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The potential for pheromone-based mating disruption of eye-spotted bud moth (ESBM), Spilonota ocellana (Denis & Schiffermüller) (Lepidoptera: Tortricidae), in apple orchards in the Okanagan Valley of British Columbia was examined in small-plot trials. In a preliminary experiment, treatment of the orchard atmosphere with a 99:1 blend of Z8-tetradecenyl acetate (Z8-14:OAc) and Z8-tetradecenyl alcohol (Z8-14:OH) completely inhibited captures of male ESBM in pheromone-baited traps, but treatment with Z8-14:OAc alone did not. Therefore, all subsequent trials used the two-component blend as a disruptant. Mean catches of male ESBM in traps baited with 0.1, 1, 10, or 20 mg of 99:1 Z8-14:OAc and Z8-14:OH were significantly reduced (81–97%) in pheromone-treated plots relative to similar traps placed in control plots. In both control and treated plots, there was a significant positive relationship between trap bait dose and trap catch. In pheromone-treated plots, this suggests that high doses of trap baits over-ride the camouflage effect of disruption or overcome the effect of sensory adaptation and habituation. The number of virgin-female baited traps capturing at least one male ESBM was reduced by 96%, and mating of virgin females on mating tables was reduced by 95% in plots treated with the two-component pheromone. The total amount of Z8-14:OAc released from pheromone disruption dispensers during the latter field trials was estimated to average 6.4 g ha-1 over 11 days or 26.4 mg ha-1 h-1. The low levels of Z8-14:OH released from disruption dispensers could not be estimated by GC analysis. Dispensers loaded with a 99:1 blend of Z8-14:OAc and Z8-14:OH were highly attractive to males in baited traps, indicating that they have the potential to induce false trail following.
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  • 23
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    Journal of insect behavior 11 (1998), S. 507-538 
    ISSN: 1572-8889
    Keywords: monarch butterflies ; Danaus plexippus ; Danainae ; Lepidoptera ; Nymphalidae ; oviposition behavior ; Asclepias ; Asclepiadaceae ; chemoreceptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The monarch butterfly, Danaus plexippus L., oviposits mainly on plants in the Asclepiadaceae, particularly within the genus Asclepias. We studied postalightment oviposition behavior of monarch females on three host species—Asclepias curassavica, A. incarnata , and A. tuberosa. After landing on the host, they used their forelegs, midlegs, and antennae to assess plant suitability. When these appendages were examined by scanning electron microscopy, contact chemoreceptor sensilla were found. In choice tests, A. incarnata was most preferred, while A. tuberosa was least preferred. However, the use of appendages varied for the different host species. Antennae were most frequently used during post-alightment behavior on A. curassavica, whereas forelegs were used more often on A. incarnata, and all three appendages were used extensively on A. tuberosa. Use of the midlegs was generally followed by use of the antennae. Tasting with either forelegs or antennae apparently may lead to egg laying on some host species. Rupture of the plant surface by midleg spines was also observed. The behavior and host preference of individual females varied significantly and may reflect differences in receptor sensitivity.
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  • 24
    ISSN: 1572-8889
    Keywords: trail following ; 5β-cholestane-3-one ; pheromone ; cooperative foraging ; social caterpillar ; bolsa ; silk ; Pieridae ; Eucheira ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The larva of the Madrone butterfly Eucheira socialis (Lepidoptera: Pieridae) secretes a trail pheromone from the ventral surface of the posterior tip of its abdomen. Caterpillars mark trails by bringing the secretory site into brief contact with the substrate during a locomotive cycle. Foragers mark most heavily when they move onto new branches and little, if at all, when they move over established trails or when they return to the communal shelter after feeding. The caterpillars make careful comparisons of alternative pathways at choice points and select newer and stronger trails over older and weaker trails. Differential marking of new and established trails during nightly forays, coupled with sensory discrimination of trails by strength and age, leads colonies to abandon old trails in favor of new trails. When applied at a rate as low as 2.5 × 10 −10 g/mm, caterpillars followed synthetic trails prepared from 5β-cholestane-3-one, a trail pheromone previously reported from the tent caterpillars (Malacosoma spp.). Although both Eucheira and Malacosoma mark with the tip of the abdomen and have near-identical sensitivites to 5β-cholestane-3-one, our study shows that Eucheira employs a relatively unsophisticated system of trail-based communication and does not recruit to food. The trail-based communication system of Eucheira appears to represent an early stage in the evolution of cooperative foraging that is derived from, and motivationally linked to, conflict behavior.
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  • 25
    ISSN: 1572-8889
    Keywords: radar tracking ; harmonic radar ; foraging flight ; Lepidoptera ; Agrotis segetum
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  • 26
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    Journal of insect behavior 11 (1998), S. 343-359 
    ISSN: 1572-8889
    Keywords: Agrotis segetum ; Lepidoptera ; Noctuidae ; turnip moth ; reproduction ; sex ratio ; reproductive capacity ; sexual selection ; mate discrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We investigated the lifetime mating potential and the reproductive behavior of male and female turnip moths Agrotis segetum (Schiff.) under field and laboratory conditions. The sex ratio was 1 : 1 in a lab-reared population as well as in two wild populations. Males were capable of mating repetitively a relatively large number of times (mean of 6.7 ± 2.7 matings) when given access to new virgin females throughout their lifetimes. Females seldom mated more than once (mean ± 1.3 ± 0.6 matings), indicating a male-biased operational sex ratio. The mean potential lifetime mating was five times higher in males, while the coefficient of variance was lower in males. There was no differences in longevity between animals that were allowed to mate and animals not allowed to mate, indicating no direct costs or benefits of mating in physiological terms. In males, the number of matings was positively correlated with longevity, but this was not the case in females. Nor was there a correlation between the number of female matings and the number of fertilized eggs. There was a negative correlation between the number of eggs fertilized and the number of times males had previously mated, indicating that male ejaculates were limited. Male spermatophore size also decreased with number of achieved matings. Laboratory-reared females attracted males in the field throughout their lifetimes, with a peak at 3–7 days of age. Wild males, allowed to choose between pairs of caged females in the field, were attracted in equal numbers to females of different ages. Females did not show any mate-rejection behavior in the field. They mated with the first male that courted them. No incidence of mate replacement by males arriving later to already courted females were recorded.
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  • 27
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    Cellular and molecular life sciences 40 (1984), S. 1004-1006 
    ISSN: 1420-9071
    Keywords: Rat ; adrenocortical responsiveness ; ACTH ; plasma ; corticosterone ; plasma ; corticotropin releasing factor (CRF)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the course of studying the plasma adrenocorticotropic hormone (ACTH) and corticosterone responses to synthetic corticotropin releasing factor (CRF), we noted some disparity in the responses. A higher dose (20 μg compared with 5 μg per rat i.a.) produced an equal plasma ACTH but greater plasma corticosterone response in adult male rats. Thus, we examined the possibility that CRF increases adrenocortical responsiveness to ACTH. CRF significantly (p〈0.0005) increased the plasma corticosterone response to ACTH in rats pretreated with dexamethasone. Thus, synthetic CRF increases corticosterone secretion in rats not only by stimulating ACTH secretion, but also by increasing the adrenocortical responsiveness to ACTH.
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  • 28
    ISSN: 1420-9071
    Keywords: Mating ; pheromone ; epoxyheneicosadiene ; enantiomer ; Arctiidae ; Callimorpha ; Tyria ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract It has been suggested that a common sex pheromone composition may account for interspecific sexual interactions observed with certain moths in the Arctiidae. In this study, it is demonstrated that the sex pheromones released by females of the Scarlet Tiger Moth,Callimorpha dominula L., and the Cinnabar Moth,Tyria jacobaeae L., have similar activities and elute at the same retention time on analysis by coupled gas chromatography (GC)-electrophysiology with males from each species. Peak enhancement on GC, chiral GC and coupled GC-mass spectrometry using authentic compounds show that the sex pheromone for bothC. dominula andT. jacobaeae is (3Z,6Z,9S,10R)-9,10-epoxyheneicosa-3,6-diene.
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  • 29
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    Cellular and molecular life sciences 40 (1984), S. 974-975 
    ISSN: 1420-9071
    Keywords: Rat ; prostaglandins ; gastric lesion ; intragastric distension model ; stress model ; indomethacin ; somatostatin preventive effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatostatin preventive effect on the gastric lesions induced in a stress model and has no preventive effect on an intragastric distension model.
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  • 30
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    Entomologia experimentalis et applicata 36 (1984), S. 15-16 
    ISSN: 1570-7458
    Keywords: sex attractants ; Lepidoptera ; Noctuidae ; Orthosia incerta ; Orthosia cruda ; fruit pest ; Z9-14:Ac ; Z9-14:Ald ; Z11-16:Ac ; Z11-16:Ald
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  • 31
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    Entomologia experimentalis et applicata 35 (1984), S. 159-167 
    ISSN: 1570-7458
    Keywords: Lepidoptera ; Geometridae ; Ectropis excursaria ; larval dispersal ; colour polymorphism ; phototaxis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung Acht Experimente wurden durchgeführt, um einige der Faktoren zu studieren, die das Wanderverhalten der Larven (Raupen) eines polyphagen Geometriden (Ectropis excursaria (Guenée)) beein-flussen. 1. Larven sind positiv phototaktisch. Die positive Phototaxis ist negativ mit Fasten, Alter und Populationsdichte korreliert. Bei hohen Temperaturen ist sie nicht mehr nachweisbar. 2. Das Wanderverhalten der Larven wird durch die Populationsdichte beeinflußt, wodurch annähernd eine konstante Dichte erhalten bleibt. Das Verhalten der individuellen Larven is dabei nicht statistisch homogen. Es gibt ‘Wanderer’ und ‘Nicht-Wanderer’. 3. Diese Verhaltensunderschiede stehen möglicherweise im Zusammenhang mit physiologischen und morphologischen Faktoren, die den individuellen Fortpflanzungserfolg und das überleben beeinflussen können; ‘Wanderer’ sind dunkler, entwickeln sich schneller und das Gewicht ihrer Puppen ist niedriger als das der ‘Nicht-Wanderer’. 4. Eine der larvalen Farbvarianten zeigte eine Präferenz für einen von zwei angebotenen Hintergründen.
    Notes: Abstract The dispersive behaviour of larvae of a polyphagous, wide-spread geometrid (Ectropis excursaria (Guenée)) was studied by examining responses to environmental and endogenous variables. It was found that differences in behaviour can be affected by environmental factors such as light, temperature, density, and plant background as well as some physiological and morphological features. The implications of these relationships are discussed as adaptative strategies to a varying environment.
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  • 32
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    Entomologia experimentalis et applicata 35 (1984), S. 177-193 
    ISSN: 1570-7458
    Keywords: induction of feeding preference ; host plants ; non-host plants ; Manduca sexta ; Sphingidae ; Lepidoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Vingt-deux espèces de plantes, dont 10 planteshôtes (Solanées), ont été testés comme plantes alimentaires pour des chenilles de ler stade de Manduca sexta. Sur cet ensemble, seulement 12 plantes (dont 9 plantes hôtes) induisaient la prise de nourriture et permettaient la croissance jusqu'au 5ème stade. La diversité des résultats suggère que les plantes pouvaient être classées en hôtes, non-hôtes acceptables et non-hôtes refusés. En utilisant le test du choix alimentaire préférentiel entre deux rondelles de feuilles, les chenilles néonates de ler stade ont préféré nettement les plantes-hôtes aux autres. Cette préférence initiale pour les plantes-hôtes était préservée quand les cheniles étaient élevées sur plantes-hôtes, mais devenait moins nette ou disparaissait pour des chenilles élevées sur d'autres plantes acceptées. Ainsi l'oligophagie ches M. sexta n'est pas induite, mais doit être héritée. Les chenilles néonates, aussi bien que celles de 5ème stade, présentent des préférences hiérarchisées parmi les plantes hôtes ou non. La seule frontiere nette observée était entre espèces de plantes acceptables ou non. Les hiérarchies préférentielles des chenilles du 5ème stade différaient légèrement lors-qu'elles avaient été élevées sur deux plantes-hôtes différentes. La différence essentielle était l'observation d'une préférence accrue pour l'espèce ayant servi à l'élevage, mais deux autres plantes-hôtes changaient aussi de position hiérarchique. La cause de ces changements de préférence a été approfondie, les chenilles étant élevées sur des feuilles de chaque espèce acceptable (hôte ou non). Leurs préférences alimentaires ont été définies en utilisant des combinaisons diverses (hôte x hôte, hôte x non-hôte acceptable, non-hôte acceptable x non-hôte acceptable). L'induction de la préférence alimentaires a été obtenue dans ces trois associations. Ceci montre que l'induction des choix alimentaires chez M. sexta n'est pas limitée aux plantes-hôtes. Le degré d'induction de la préférence alimentaire variait de très fort à indécelable; il dépendait de l'association examinée. La source de la variabilité de cette induction a été examinée en fonction de la relation entre la force de l'induction et les rapports taxonomiques des plantes associées. La relation obervée était inversée pour M. sexta. L'examen des données de la littérature ont révélé une relation du même type pour les autres espèces de Lépidoptères.
    Notes: Abstract Ten host plant (Solanaceae) and twelve non-host plant species were tested as foodplants for first instar larvae of the tobacco hornworm, Manduca sexta. Only nine host and three non-host plant species elicited feeding and supported growth up to fifth instar. The range of acceptability suggested that plants be divided into hosts, acceptable non-hosts, and unacceptable non-hosts. Using the two-choice feeding preference test we found that the initial preference for hosts was preserved when larvae were reared on hosts, but was less strong or absent for larvae reared on acceptable non-hosts. Thus oligophagy in the tobacco hornworm is not induced, but must be inherited. Newly-hatched first instar larvae and fifth instar larvae showed a preference hierarchy among both hosts and non-hosts. Fifth instar larvae reared separately on two different host species showed slightly different preference hierarchies among hosts. The preference for the rearing plant was increased and also two other host species changed positions in hierarchies. Feeding preferences of larvae reared on hosts or acceptable non-hosts were determined using plant combinations of host vs. host, host vs. acceptable non-host, and acceptable non-host vs. acceptable non-host. Induction of feeding preference was found in all three of these categories. This shows that induction of feeding preference in the tobacco hornworm is not restricted to host plant species. The degree to which feeding preferences were induced ranged from very strong to undetectable and dependend on the plant species paired. The strength of induction in the tobacco hornworm was found to correlate inversely with taxonomic relatedness of the plant species paired. Analysis of induction data from the literature revealed a similar correlation for other lepidopteran species.
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  • 33
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    Entomologia experimentalis et applicata 35 (1984), S. 255-261 
    ISSN: 1570-7458
    Keywords: method ; dry matter ; budget ; Lepidoptera ; phytophagous ; gravimetry ; area ; accuracy ; precision
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Les budgets en matière sèche consommée par des lépidoptères ont été comparés par les méthodes gravimétrique et planimétrique. La méthode gravimétrique est basée sur le rapport poids sec/poids frais de feuilles consommées par les chenilles. Avec la méthode planimétrique, la quantité d'aliment proposée aux chenilles est déterminée par les tracés de la surface des feuilles et le contenu de matière sèche par unité de surface des feuilles. La méthode de planimétrie permet l'utilisation de plus grands rameaux de feuilles et de cages d'élevage extérieures en gaze. Il n'y avait pas de différence appréciable dans les éléments du budget (croissance, ingestion et déjection), ni aucune différence dans la variabilité observée des données attribuable à la méthode utilisée. Cependant, la variabilité attendue d'après la précision des mesures avec la méthode gravimétrique est inférieure à celle de la méthode planimétrique. est inférieure à celle de la méthode planimétrique. Des éléments expérimentaux, inhérents à la méthode gravimétrique, introduisent une variabilité dans les mesures que l'on n'a pas avec la méthode planimétrique. 30–60% de la variabilité dans la consommation ont été attribués à des paramètres internes à la chenille, même quand elles provenaient toutes de la même ooplaque.
    Notes: Abstract Gravimetric and a combination areal-gravimetric methods for determining dry matter budgets for leaf eating Lepidoptera were compared. The gravimetric method is based on dry weight/live weight ratios of the leaves fed to the larvae. In the areal-gravimetric method, the quantity of food offered to the larvae is determined from the area of leaf tracings and the dry matter content per unit area of the leaves. The areal-gravimetric method permits the use of larger leaf sprays and an open, gauze enclosed rearing chamber. There were no consistent differences in budget factors (growth, ingestion or egestion), nor were there any differences in the observed variability of the data attributable to the method used. However, the expected variability based on instrument precision for the gravimetric method is less than for the areal-gravimetric method. Experimental factors inherent in the gravimetric method introduce variability to the measurements that are not present in the areal method. Thirty to 60% of the variability in budget factors was attributed to intrinsic properties of the larvae, even though the larvae were taken from the same egg masses.
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    Journal of comparative physiology 178 (1996), S. 55-61 
    ISSN: 1432-1351
    Keywords: Electrophysiology ; Lepidoptera ; Photoreceptor ; Spectral sensitivity ; Vision
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    Topics: Biology , Medicine
    Notes: Abstract 1. The ommatidia of the butterfly Papilio have a fused and tiered rhabdom. The distal tier of the rhabdom is made up of four distal photoreceptors (R1–4), whereas the proximal tier is made up of four proximal (R5–8) and one basal photoreceptor cell (R9). 2. We first confirmed by light microscopy that the ommatidia of Papilio are not twisted, i.e. have the same spatial organization all about the longitudinal axis. The polarization method, previously applied to the distal tier, hence is applicable to identify the photoreceptor location from the peak angle of the polarization sensitivity. 3. We determined the polarization and spectral sensitivity of in total 109 proximal and basal photoreceptors in the lateral looking eye region. All of the photoreceptors were either green or red type, most of which fall into three classes as judged by the peak angles of the polarization sensitivity: around 40°, 150°, and 180° (= 0°) with respect to the dorso-ventral axis. The first two classes are formed by the proximal photoreceptors with straight microvilli oriented at the average angle of 39° (R6, 8) and 144° (R5, 7) respectively, and the third is formed by the basal photoreceptors R9 with straight microvilli oriented at 180° (= 0°). The mean polarization sensitivity (PS = maximal sensitivity/minimal sensitivity) was about 2. 4. 75% of the proximal and 48% of the basal photoreceptors were of the red type. 5. A single ommatidium of Papilio appears to contain two to four types of spectral receptors.
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  • 35
    ISSN: 1432-1351
    Keywords: Heliothis ; Noctuidae ; Lepidoptera ; Plume structure ; Behavior
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    Notes: Abstract 1) Male Heliothis virescens moths flew upwind to pulsed pheromone plumes. Upon truncation of the pulsed plume males flew into clean air, turning their tracks crosswind (〉 60° relative to directly upwind direction at 0°) within an average of 0.27 s, and were casting, perpendicular to the wind-line (90°), within 0.43 s. 2) The characteristic casting flight in clean air consisted of left-right crosswind reversals, continuing for many seconds without further pheromonal stimulation. Males intercepting a single strand of pheromone during casting flight responded by surging upwind (track angles 〈 60°). The phasic surge lasted only 0.38 s before reverting to crosswind flight (〉 60°). 3) Average templates of responses in two and three dimensions were created. Males controlled their vertical deviations very tightly when in contact with pheromone but upon entering clean air, lateral and vertical excursions became much greater. 4) Males failed to sustain upwind flight to repetitively pulsed plumes generated at 〈 4 filaments/s. At the threshold frequency of 4 pulses/s we show that upwind flights were composed of reiterated surges followed by crosswind casting. As the pulse frequency increased, the tracks became straighter and the single filament cast-surge-cast template could be viewed only sporadically when, for example, a male apparently failed to intercept filaments.
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  • 36
    ISSN: 1573-0603
    Keywords: Brain ; Histology ; Organotypic culture ; Patch clamp recording ; Rat
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    Topics: Biology
    Notes: Abstract The goal of the current research was to define an in vitro system that can replace in vivo experimentation but reflects as far as possible aspects of the intact situation of the developing nervous system of mammals. Tissue slices of postnatal rat hippocampi were continuously moved between the medium and gas phase. Under these conditions the complex cytoarchitecture was preserved for many weeks. Lactate dehydrogenase assay, cell size analysis and neuron- and glial cell specific immunocytochemical markers were employed to illuminate explant development in vitro. By scanning electron microscopy the explant surface was analysed in order to determine the conditions suitable for patch clamp recording. Electrophysiological analysis revealed a pronounced spontaneous activity showing the neurons to be functionally active. These data indicate that organotypic roller cultures reflect to a large extent the in vivo situation of the mammalian nervous system. The culture system provides a promising model system for developmental physiology, neurotoxicology and pharmacology.
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  • 37
    ISSN: 1420-9071
    Keywords: Rat ; cerebrospinal fluid, human ; analgesia ; naloxone ; pain indifference, congenital ; opiates, endogenous
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    Notes: Summary CSF from a patient with congential indifference to pain was found to produce analgesia in the rat following intracerebroventricular injections. The analgesic effect was attenuated by pretreatment with naloxone suggesting the involvement of hyperactive endogenous opiate mechanisms in this patient.
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  • 38
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    Cellular and molecular life sciences 40 (1984), S. 1368-1369 
    ISSN: 1420-9071
    Keywords: Rat ; kidney ; hypertensive ; prostaglandin dehydrogenase ; hexokinase
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    Topics: Biology , Medicine
    Notes: Summary 15-Hydroxyprostaglandin dehydrogenase (PGDH) surged in hypertensive (SHR) and normotensive (WKY) rat kidney at 8 days of age, is greatest in SHR. Hexokinase fell in SHR at 17 days of age, but thereafter was similar to WKY. This suggests multisystem enzymatic abnormalities in SHR kidney during development of hypertension.
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  • 39
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    Cellular and molecular life sciences 52 (1996), S. 259-263 
    ISSN: 1420-9071
    Keywords: Senecio cannabifolius ; Compositae ; foliar surface chemistry ; tobacco cutworm ; Spodoptera litura ; Lepidoptera ; Noctuidae growth inhibition ; ethyl (1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl) acetate ; methyl (1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl) acetate
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    Notes: Abstract Dewaxed leaf surface extracts of 12 plants from Hokkaido, prepared by dipping fresh leaves in chloroform for 3 min, were used in a choice leaf-disk bioassay against larvae of the tobacco cutwormSpodoptera litura. Activity was found only in the extract ofSenecio cannabifolius, a very successful weed in Hokkaido. Individual fractions of the extract, however, were not active. Incorporation of the individual fractions of the surface extracts as well as fractions of the methanolic extracts of the leaf residue into an artificial diet fed to neonateS. litura led to the isolation of ethyl (1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl) acetate, the major surface compound, as the active principle. This compound was also present in the methanolic extract of the leaf residue together with methyl (1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl) acetate, which had the same growth inhibitory effect on the larvae. The presence of these compounds in the foliar surface and tissue suggests a defensive role against herbivores.
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  • 40
    ISSN: 1423-0445
    Keywords: sex pheromone ; synergist ; antagonist ; mate recognition ; reproductive isolation ; chemotaxonomoy ; phylogeny ; evolution ; Lepidoptera ; Tortricidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The geometric isomers (E,E)-, (E,Z)-, (Z,E)-, and (Z,Z)-8,10-dodecadien-1-yl acetate were identified as sex pheromone components or sex attractants in the tribes Eucosmini and Grapholitini of the tortricid subfamily Olethreutinae. Species belonging to the more ancestral Tortricinae were not attracted. Each one isomer was behaviourally active in males ofCydia andGrapholita (Grapholitini), either as main pheromone compound, attraction synergist or attraction inhibitor. Their reciprocal attractive/antagonistic activity in a number of species enables specific communication with these four compounds.Pammene, as well as otherGrapholita andCydia responded to the monoenic 8- or 10-dodecen-1-yl acetates. Of the tribes Olethreutini and Eucosmini,Hedya, Epiblema, Eucosma, andNotocelia trimaculana were also attracted to 8,10-dodecadien-1-yl acetates, but several otherNotocelia to 10,12-tetradecadien-1-yl acetates. The female sex pheromones ofC. fagiglandana, C. pyrivora, C. splendana, Epiblema foenella andNotocelia roborana were identified. (E,E)- and (E,Z)-8,10-dodecadien-1-yl acetate are producedvia a commonE9 desaturation pathway inC. splendana. CallingC. nigricana andC. fagiglandana females are attracted to wingfanning males.
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  • 41
    ISSN: 1423-0445
    Keywords: protein solubility ; insect yolk protein ; buffering capacity ; phenolics ; Lepidoptera ; gypsy moth ; Lymantria dispar ; Malacosoma disstria ; Choristoneura rosaceana
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A standard buffer (5 mM phosphate at pH 7) which is used to extract protein from insect eggs provided complete protein solubility for eggs from three of four tree-feeding lepidopteran species: obliquebanded leaf roller (Choristoneura rosaceana), forest tent caterpillar (Malacosoma disstria), and the eastern tent caterpillar (Malacosoma americanum). Under the same extraction protocol, egg proteins from the gypsy moth (Lymantria dispar), remained nearly insoluble. An array of methods typically used to solubilize insect egg proteins were tried and all but the most denaturing (2% SDS) were ineffective. Extraction buffers with typically high pH values were then evaluated. The results indicated that 1) solubility of gypsy moth egg proteins was pH dependent, and full solubility of most egg proteins required the extraction buffer to have a pH of 12 or more prior to the addition of eggs. We also determined that 2) the gypsy moth egg has a buffering capacity which must be surpassed for complete protein extraction, 3) low salt/high pH buffers gave slightly higher total protein values than did high salt/high pH buffers, 4) parental nutritional history (host species utilized) and egg developmental state (pre-embryonatedvs postembryonated/pre-hatch) were unrelated to the requirements for complete egg protein solubilization, and 5) the presence of soluble phenolics, compounds that have the potential to bind to protein and cause insolubility, was confirmed for the gypsy moth egg with 2-D paper chromatography and several other tests. Based on these results, we present a hypothesis about the cause of egg protein insolubility in the gypsy moth.
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  • 42
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    Cellular and molecular life sciences 40 (1984), S. 1008-1010 
    ISSN: 1420-9071
    Keywords: Rat ; ethanol preference ; acetaldehyde self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Peripherally self-injected acetaldehyde in interaction with environmental and nutritional variables significantly enhances alcohol drinking in rats and suggests an involvement of acetaldehyde in voluntary alcohol intake.
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  • 43
    ISSN: 1432-1211
    Keywords: Key words CD1 ; Rat ; Gene ; Organization ; Polymorphism
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    Topics: Biology , Medicine
    Notes: Abstract  The non-major histocompatibility complex (MHC)-encoded CD1 family has recently emerged as a new antigen-presenting system that is distinct from either MHC class I or class II molecules. In the present study, we determined the genomic structure of the rat CD1 locus. It was extremely similar to mouse CD1 genes, especially to CD1D1. The 5′ flanking region of the CD1 gene contained the binding motifs for two cytokine-inducible transcription factors, NF-IL2-A and NF-IL6. Some regulatory elements found in MHC class I genes (enhancer A, enhancer B, and the IFN response element) were absent. It is of interest that a tyrosine-based motif for endosomal localization found in the human CD1b cytoplasmic tail was encoded by a single short exon which was conserved in all CD1 molecules except for CD1a. Southern blot and direct sequencing analyses of inbred rat strains suggested very limited polymorphism in the 5′ region where a hydrophobic ligand-binding groove is encoded; a single base substitution resulted in amino acid alteration of alanine (GCT) to valine (GTT) at codon 119. Comparison of the overall exon-intron organization of CD1 genes revealed that the length of the intron was also characteristic to each of the two classes of CD1 genes, classic CD1 and CD1D; such categorization has hitherto been made according to the sequence similarity of the coding region. This finding provides further support for the hypothesis that the two classes have different evolutionary histories. In contrast to the complete absence of the classic CD1 in rats and mice, the entire region of nonpolymorphic CD1D has been conserved through mammalian evolution. Similar functional properties of rodent CD1 and human CD1d are implied.
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  • 44
    ISSN: 1432-1211
    Keywords: Key words RT1.S3 ; Grc ; MHC ; Class I ; Rat
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    International journal of biometeorology 41 (1998), S. 101-104 
    ISSN: 1432-1254
    Keywords: Key words Space flight ; Rat ; Plantaris muscle ; GLUT-4 ; Citrate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract  The effects of 14 days of space flight on the glucose transporter protein (GLUT-4) were studied in the plantaris muscle of growing 9-week-old, male Sprague Dawley rats. The rats were randomly separated into five groups: pre-flight vivarium ground controls (PF-VC) sacrificed approximately 2 h after launch; flight groups sacrificed either approximately 5 h (F-R0) or 9 days (F-R9) after the return from space; and synchronous ground controls (SC-R0 and SC-R9) sacrificed at the same time as the respective flight groups. The flight groups F-R0 and F-R9 were exposed to micro-gravity for 14 days in the Spacelab module located in the cargo bay of the shuttle transport system – 58 of the manned Space Shuttle for the NASA mission named ”Spacelab Life Sciences 2”. Body weight and plantaris weight of SC-R0 and F-R0 were significantly higher than those of PF-VC. Neither body weight nor plantaris muscle weight in either group had changed 9 days after the return from space. As a result, body weight and plantaris muscle weight did not differ between the flight and synchronous control groups at any of the time points investigated. The GLUT-4 content (cpm/µg membrane protein) in the plantaris muscle did not show any significant change in response to 14 days of space flight or 9 days after return. Similarly, citrate synthase activity did not change during the course of the space flight or the recovery period. These results suggest that 14 days of space flight does not affect muscle mass or GLUT-4 content of the fast-twitch plantaris muscle in the rat.
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  • 46
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    Oecologia 108 (1996), S. 643-651 
    ISSN: 1432-1939
    Keywords: Migration rate ; Lepidoptera ; Mark-recapture study ; Population density ; Movement behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Rapidly increasing fragmentation of natural landscapes decreases the ability of many species to reach the smaller and more isolated patches of habitat in a metapopulation. The densities of local populations of several moth species and the butterfly Hipparchia semele in a network of small islands, and the rates of inter-island movement and movement patterns, were investigated, to determine the factors affecting the rate and pattern of movements. The estimated population densities ranged from 0.001 to 0.2 individuals/m2. The observed emigration and immigration rates depended on island isolation and various traits of the species, with great variability in migration rates among species. Thin-bodied, slow-flying species did not move among the islands, whereas many robust, fast-flying species moved among the islands relatively frequently. Migration rate increased significantly with body size and was significantly higher in oligophagous than in polyphagous species, suggesting that these factors are important determinants of the migration rate of the species. Migration rate was low when the surface temperature of the sea was low, and a greater proportion of individuals emigrated from small than large patches of habitat. The migration distances of female noctuids were shorter than those of males and those of both sexes of the butterfly H. semele. The observed movement patterns are consistent with a metapopulation structure in most of the moth species.
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  • 47
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    European journal of clinical pharmacology 49 (1996), S. 387-391 
    ISSN: 1432-1041
    Keywords: Key words Liver function tests; elderly ; pharmacokinetics ; geriatrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66–92 y) and 12 healthy volunteers (20–35 y). Methods: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). Results: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 μmol*h⋅l−1, clearance was reduced (5.0 vs. 11.8 l⋅h−1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P 〈 0.0001). Conclusion: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
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  • 48
    ISSN: 1432-1041
    Keywords: Antiallergic drug ; FK613 ; pharmacokinetics ; histamine skin-test ; drug formulation ; urinary excretion ; safety
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetic and pharmacodynamic properties of FK613, a novel indolyl piperidine derivative, were investigated after oral administrations of 5, 10 and 20 mg in hard gelatin capsules to healthy male volunteers. FK613 was rapidly and almost completely absorbed, and 〉89% was recovered in the urine as the unchanged form. The urinary excretion of FK613 was linearly correlated with plasma concentration and its low water solubility was the main concern regarding the safety. In another experiment using a double-blind crossover design, in which 0 (placebo), 5 and 20 mg FK613 were administered to determine the plasma concentration-effect relationship, suppression of the intradermal histamine-induced skin reaction by FK613 was observed. Thus, the maintenance of a plasma concentration of FK613 in the range of 80–250 ng · ml-1 was recommended to ensure the suppression of histamine-induced wheal by 〉50% and not to exceed the solubility in urine. To achieve this, a new hydrogel-type formulation of FK613 was developed, with the aim both of delaying its absorption, so as to suppress the sharp rise in plasma concentration, and of maintaining the effective concentration for a longer period of time. This formulation was administered after meals at the doses of 20, 30, 40, 50 and 60 mg, and at repeated doses of 40 mg twice daily for 6.5 days to evaluate the pharmacokinetics and safety in healthy subjects. The area under the plasma concentration curve increased linearly with dose, whereas maximum plasma concentration (Cmax) tended to peak as dose increased, indicating the desirable properties of this formulation. Although Cmax exceeded 250 ng/ml at doses of 30 mg or more, no urinary crystal formation was observed on careful inspection of urine.
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  • 49
    ISSN: 1432-1041
    Keywords: Key words Tiludronate; healthy volunteers ; bisphosphonates ; pharmacokinetics ; calcium metabolism ; bone resorption ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: A double-blind, placebo-controlled study was conducted to assess the pharmacokinetics and pharmacodynamics of the bisphosphonate tiludronic acid, administered once daily as sodium tiludronate 200, 400, 600 and 800 mg for 12 days. Four groups of ten subjects participated in the study, with a drug to placebo ratio of 4:1. Methods: Pre-dose blood samples were taken on alternate days, starting on Day 1 and additional samples were collected over 144 h following the final dose on Day 12. Urine was collected over 24 h after the final dose. Indices of calcium homeostasis and biochemical markers of bone turnover were assessed during the study as pharmacodynamic parameters. Tolerability was evaluated with special emphasis on renal function and gastrointestinal irritation. Adverse experiences were assessed at regular time intervals. Results and conclusions: Steady state was attained from Day 4 (200 mg) or from Day 6 (400, 600 and 800 mg). Following the final dose on Day 12, minimal plasma concentrations (Cmin) ranged between 0.19 and 1.5 mg ⋅ l−1, and maximal plasma concentrations (Cmax) between 1.1 and 7.8 mg⋅l−1 for the lowest and highest doses, respectively. A supra-proportional increase in Cmax, AUC24 and Ae 24 with dose was observed. There was a linear relationship between the plasma tiludronic acid and its urinary excretion rate, so, the disproportional rise in Cmax and AUC24 with increasing dose could not be attributed to saturation of renal excretion. Certain indices of calcium homeostasis changed significantly during the study, but generally, became only prominent at the highest dose level of 800 mg. Total serum calcium and the urinary calcium/creatinine clearance ratio fell, indicating depression of osteoclastic bone resorption, which was not revealed by serum osteocalcin levels probably because of the brevity of the treatment (12 days). In response to the decline in serum calcium, serum 1,25-dihydroxyvitamin D3 and intact PTH (1–84) levels increased. None of the safety parameters raised any concerns about the safety of sodium tiludronate administered in this way.
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  • 50
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    European journal of clinical pharmacology 51 (1996), S. 189-193 
    ISSN: 1432-1041
    Keywords: Key words Dihydropyridine ; Amlodipine ; Grapefruit juice; flavonoids ; interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: This study was performed to assess whether coadminstration with grapefruit juice significantly affects the pharmacokinetics of amlodipine, a dihydropyridine class calcium antagonist with slow absorption, distribution and low plasma clearance. The primary objective was to evaluate whether short exposure to grapefruit juice could affect the metabolism of amlodipine to an extent similar to that previously demonstrated for other dihydropyridines (e.g. felodipine, nisoldipine, nitrendipine). Methods: Twelve healthy male volunteers followed a randomised, open crossover study design, comparing the effect of a single oral dose of amlodipine (5 mg) taken together with a glass of grapefruit juice (250 ml) vs water. Blood samples to determine plasma concentration were taken and blood pressure (BP) and heart rate (HR) were measured throughout the study. Results: When amlodipine was coadministered with grapefruit juice, Cmax was 115% and AUC(0–72 h) was 116% compared with water, but tmax was not significantly changed. There were no significant differences in BP and HR between the two treatments. A small decrease in diastolic BP, however, was observed in both treatments 4–8 h after drug administration, coinciding with Cmax, but this was normalised after 12 h. The BP reduction seen was compensated by a slight increase in HR, which remained throughout the study. Conclusion: An interaction between grapefruit juice and amlodipine was demonstrated. The haemodynamic data showed that a dose of 5 mg was sufficient to achieve a BP reduction in healthy subjects, but the increase in amlodipine plasma concentration seen after intake of grapefruit juice was too small to significantly affect BP or HR. The clinical significance of this food/drug interaction, however, cannot be ignored since there is considerable variation between individuals and a more extensive intake of grapefruit juice might give more pronounced effects.
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  • 51
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    European journal of clinical pharmacology 51 (1996), S. 259-264 
    ISSN: 1432-1041
    Keywords: Key words Nebivolol ; Hypertension; d ; l-enantiomers ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Nebivolol is a selective β1-adrenergic receptor blocker possessing an ancillary vasodilating effect. The objective of the present study was to study the haemodynamic and pharmacokinetic properties of nebivolol 5 mg once daily in a double-blind, placebo-controlled cross-over study. Methods: Fifteen patients, 12 men and 3 women, with essential hypertension were investigated. Blood pressure and peripheral circulation were determined after acute oral nebivolol administration, 5 mg daily, and after 4 weeks treatment. Results: The acute effect on blood pressure upon single-dosing was weak and non-significant. After 4 weeks both systolic blood pressure (152 vs 163 mmHg) and diastolic blood pressure (89 vs 97 mmHg) were significantly reduced after nebivolol treatment as compared to placebo. Following the first dose the venous volume was higher on placebo (5.88 ml ⋅ 100 ml−1 tissue) as compared to active nebivolol treatment (5.17 ml ⋅ 100 ml−1 tissue), while there were no statistically significant differences with regard to venous plethysmographic findings after 1 month on placebo (5.53 ml ⋅ 100 ml−1 tissue) or on active treatment (5.97 ml ⋅ 100 ml−1 tissue). Calculated peripheral resistance did not differ between active treatment (617 units) or placebo (548 units) after the first dose, whereas it was significantly lowered after 4 weeks of nebivolol treatment (483 units) as compared to placebo (593 units). Conclusions: Oral nebivolol 5 mg once daily lowered blood pressure and heart rate during steady state compared to placebo. Moreover, venous volume was reduced during acute but not steady-state dosing, while peripheral resistance was unaffected in the acute phase but reduced during steady state. Plasma concentrations of the separate enantiomers plus hydroxylated metabolites after the first and last dose in hypertensive patients were similar to those in healthy subjects.
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  • 52
    ISSN: 1432-1041
    Keywords: Key words Pantoprazole; Proton pump inhibitor drug interaction ; oral anticoagulant phenprocoumon ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon. Methods: Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30–40% of normal within the first 5–9 days and to maintain this level. The individual maintenance doses remained unaltered from day 9 on and were administered until day 15. Additionally, on study days 11–15, pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria. Results: The equivalence ratio (test/reference) for prothrombin time ratio was 1.02 (90% confidence interval 0.95–1.09), thus fulfilling predetermined bioequivalence criteria (0.70–1.43). The pharmacokinetic characteristics AUC0–24h and Cmax of S(−)-and R(+)-phenprocoumon were also investigated using equivalence criteria. Equivalence ratios and confidence limits of AUC0–24h and of Cmax of S(−)-phenprocoumon (0.93, 0.87–1.00 for AUC0–24h; 0.95, 0.88–1.03 for Cmax) and of R(+)-phenprocoumon (0.89, 0.82–0.96; 0.9, 0.83–0.98) were within the accepted range of 0.8–1.25. Conclusion: Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated.
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  • 53
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    European journal of clinical pharmacology 49 (1996), S. 387-391 
    ISSN: 1432-1041
    Keywords: Liver function tests ; elderly ; pharmacokinetics ; geriatrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66–92 y) and 12 healthy volunteers (20–35 y). Methods: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). Results: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 μmol*h·l−1, clearance was reduced (5.0 vs. 11.8 l·h−1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r=0.41, P=0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r=0.94, P〈0.0001). Conclusion: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
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  • 54
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    European journal of clinical pharmacology 49 (1996), S. 411-415 
    ISSN: 1432-1041
    Keywords: Moxisylyte ; pharmacokinetics ; intracavernous administration ; healthy volunteers ; adverse events ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The concentration-time profiles of specific metabolites of moxisylyte, an α-adrenoceptor blocking agent, in the plasma and urine from 18 healthy volunteers were investigated after intracavernous (IC) administrations at three dose levels (10, 20 and 30 mg). Results: Four metabolites, unconjugated desacetyl-moxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulphates were found in plasma and urine. For all metabolites, t1/2 elimination was independent of the administered dose (1.19 h for unconjugated DAM; 1.51 h for DAM glucuronide; 1.51 h for DAM sulphate; and 2.17 h for MDAM sulphate). Cmax and AUC increased in direct proportion to dose, except for the inactive DAM glucuronide. Any the differences detected were small and equivalence of the three doses can be accepted. Conclusion: The pharmacokinetics of moxisylyte in humans following intracavernous administration were linear in the dose range 10 to 30 mg.
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  • 55
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    European journal of clinical pharmacology 49 (1996), S. 293-298 
    ISSN: 1432-1041
    Keywords: Key words Budesonide; enema ; pharmacokinetics ; healthy subjects ; hepatic bypass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2–43%) and 15% (3.2–50%) after rectal administration and 6.3% (2.4–10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol ⋅ l−1 (0.95–8.2), 3.0 nmol ⋅ l−1 (0.64–8.9) and 1.3 nmol ⋅ l−1 (0.61–3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax = 1.3 h for both formulations (range 0.5–2.0)], but was slower after oral dosing [tmax = 2.1 h (1.0–6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55–99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.
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  • 56
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    European journal of clinical pharmacology 49 (1996), S. 293-298 
    ISSN: 1432-1041
    Keywords: Budesonide ; enema ; pharmacokinetics ; healthy subjects ; hepatic bypass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2–43%) and 15% (3.2–50%) after rectal administration and 6.3% (2.4–10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol·l-1 (0.95–8.2), 3.0 nmol·l-1 (0.64–8.9) and 1.3 nmol·l-1 (0.61–3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax=1.3 h for both formulations (range 0.5–2.0)], but was slower after oral dosing [tmax=2.1 h (1.0–6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55–99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.
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  • 57
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    European journal of clinical pharmacology 49 (1996), S. 317-323 
    ISSN: 1432-1041
    Keywords: Magnesium ; Plasma level ; pharmacokinetics ; bioavailability ; circadian fluctuation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.
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  • 58
    ISSN: 1432-1041
    Keywords: Key words Tolcapone ; Elderly; levodopa ; pharmacokinetics ; pharmacodynamics ; multiple-dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: The purpose of this study was to assess the multiple-dose clinical pharmacology of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor, in elderly subjects. Methods: The drug was administered orally t.i.d. for 7 days to four sequential groups of eight elderly subjects (gender ratio1:1) at doses of 100, 200, 400 and 800 mg in a double-blind, randomised, placebo-controlled, ascending-multiple-dose design. On days 2 and 7, a single dose of levodopa/benserazide 100/25 mg was given 1 h after the first intake of tolcapone. Plasma concentrations of tolcapone, its metabolite 3-O-methyltolcapone, levodopa and 3-O-methyldopa were determined during the course of the study in conjunction with COMT activity in erythrocytes. Results: Tolcapone was well tolerated at all dose levels, with a slight increase in gastrointestinal adverse events in females at higher doses. The drug was rapidly absorbed and eliminated and showed no changes in pharmacokinetics with time during multiple doses of 100 and 200 mg t.i.d. At doses of 400 and 800 mg t.i.d., tolcapone accumulated moderately as reflected in increased Cmax and AUC values. Despite the long half-life of 3-O-methyltolcapone (39 h), only minor accumulation occurred due to suppression of its formation by tolcapone. The pharmacodynamics of tolcapone did not change during the week of treatment as reflected in inhibition of COMT activity in erythrocytes, the derived parameters of the plasma concentration-effect relationship (inhibitory Emax model with constant EC50 values) and the effect on levodopa pharmacokinetics (1.6 to 2.5-fold increase in bioavailability). This suggests the absence of tolerance development and the insignificance of the altered pharmacokinetics at 400 and 800 mg t.i.d. with regard to the pharmacodynamics. Conclusion: The results of this study offer promising perspectives for the application of tolcapone as adjunct therapy to levodopa in the treatment of Parkinson’s disease.
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  • 59
    ISSN: 1432-1041
    Keywords: Key words Cilazapril ; Caucasians ; Chinese; cilazaprilat ; pharmacokinetics ; pharmacodynamics ; ACE inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Methods: The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme (ACE) inhibitor cilazapril were studied in 12 Chinese and 13 Caucasian, healthy, normotensive volunteers on their normal diet. Cilazapril was given orally as a single 2.5 mg capsule. Plasma was sampled for assay of the active metabolite, cilazaprilat, plasma renin activity (PRA), aldosterone, angiotensin I (AI) and ACE-activity. Plasma concentrations of the active drug were measured by radioimmunoassay. Blood pressure and heart rate were measured at regular intervals. Results: The pharmacokinetic parameters of cilazaprilat were similar in the two ethnic groups. No significant difference in plasma concentrations was found at any of the time points. However, the weight-adjusted plasma clearance was significantly higher in the Chinese group, which is compatible with their lower body weight. The effects on plasma hormones were also comparable, although there was a somewhat greater rise in PRA and greater fall in aldosterone levels in Chinese than in Caucasians. The effect of cilazapril on blood pressure and heart rate was greater than was previously reported in healthy volunteers. Systolic (SBP) and diastolic (DBP) blood pressure were significantly reduced in both groups, but there was a more prolonged reduction in DBP in Caucasians. In addition, heart rate (HR) was significantly increased from baseline from 5 h onwards in Chinese subjects and significantly higher in comparison with Caucasians at most time points from 1.5 h onwards. The pharmacokinetic parameters of cilazapril were essentially the same in healthy, normotensive Chinese and Caucasians. Cilazapril reduced blood pressure acutely in both groups, with good tolerance. The inhibition of ACE in relationship to time and the plasma concentrations of cilazaprilat were similar in the two groups, although the changes in PRA and aldosterone suggest an ethnic difference in the responses of the renin-angiotensin-aldosterone system.
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  • 60
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    European journal of clinical pharmacology 50 (1996), S. 203-208 
    ISSN: 1432-1041
    Keywords: Key words Cyclosporine ; Felodipine; dehydrofelodi-pine ; pharmacokinetics ; blood pressure ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: In a double blind, randomised, placebo-controlled, cross-over study 12 healthy male volunteers were allocated to receive felodipine + placebo, cyclosporine + placebo, and felodipine + cyclosporine in order to investigate the interaction between the calcium channel blocker felodipine and cyclosporine as it affects the pharmacokinetics of felodipine, dehydrofelodipine, and cyclosporine, and 24-hour blood pressure measurements. Methods: Single doses of cyclosporine (capsules, 5 mg/kg body weight) and of felodipine (extended release (ER) tablets 10 mg) were given at a 1–2 week interval. Plasma drug concentrations were followed for 2 days after drug intake. Results: For cyclosporine, Cmax was increased after combined treatment (16%) compared to cyclosporine alone, but felodipine did not influence other kinetic parameters of cyclosporine. For felodipine, combined treatment with cyclosporine and felodipine increased AUC and Cmax (58% and 151%, respectively) and lowered mean residence time (24%) significantly compared to felodipine alone. For the metabolite dehydrofelodipine, too, AUC and Cmax were increased after the combined treatment (43% and 94%, respectively). Mean 24-hour systolic and diastolic blood pressures were significantly lower after felodipine, both when felodipine was given alone (121/68 mmHg) and in combination with cyclosporine (122/68 mmHg) compared to cyclosporine alone (127/73 mmHg). Conclusion: A combined single dose of cyclosporine and felodipine in healthy subjects increased the AUC and Cmax of felodipine suggesting a cyclosporine-induced decrease in the first-pass metabolism of felodipine, whereas the AUC of cyclosporine was only slightly increased by felodipine.
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  • 61
    ISSN: 1432-1041
    Keywords: Key words Oxybutynin; effect of food ; N-desethyl oxybutynin ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The effect of food on the bioavailability of oxybutynin was assessed in a randomised cross-over study in 23 healthy volunteers. A single oral 10 mg dose of a controlled release oxybutynin tablet was administered after a high fat breakfast and to fasting subjects. The AUC, Cmax, tmax, t1/2 and MRT of oxybutynin and its active metabolite N-desethyloxybutynin were determined. Results: Breakfast did not change the AUC of oxybutynin but increased the AUC of N-desethyloxybutynin by about 20% . The Cmax of oxybutynin and N-desethyl oxybutynin were two-fold higher when the drug was administered after breakfast compared to the fasting state. Conclusion: Breakfast significantly reduced the MRT of oxybutynin and N-desethyloxybutynin.
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  • 62
    ISSN: 1432-1041
    Keywords: Key words Idebenone; mitochondrial encephalomyopathy ; young patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics and tolerance of idebenone after single or repeated doses have been studied in young patients with mitochondrial encephalomyopathy. Results: No significant adverse effects were noted. In 3 out of 7 patients idebenone induced overall stimulation and improvement in arousal. Plasma concentrations of idebenone and its main metabolites were determined and the pharmacokinetic parameters of idebenone after single and repeated doses were estimated. During the single dose study, the mean plasma concentrations of idebenone and its main metabolites and mean pharmacokinetic parameters were comparable to published results (Cmax = 452.2 ng ⋅ ml−1, tmax = 2.3 h, AUC = 26 μg ⋅ ml−1 ⋅ h, t1/2β = 16.5 h). During the repeated doses study, no significant difference was found between mean residual plasma concentrations of idebenone on Day 2 (47 ng ⋅ ml−1) and Day 5 (70.6 ng ⋅ ml−1), and mean t1/2β of idebenone after the single and after repeated dose studies, i.e., there was no evidence of accumulation. Although idebenone did not appear to accumulate during this study, the coadministration of anticonvulsants, often prescribed during mitochondrial encephalomyopathy, can affect its pharmacokinetics.
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  • 63
    ISSN: 1432-1041
    Keywords: Key words Amisulpride; ethanol vector ; performance ; memory ; cognitive function ; interaction ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: Amisulpride is a benzamide antipsychotic that binds selectively to dopamine D2- and D3-receptors, preferentially in limbic and hippocampal structures. Since other substituted benzamides have a limited or negligible interaction with alcohol on human performance, amisulpride was studied for this potential. Methods: In a randomised double-blind crossover study, 18 young, non-smoking men took single oral doses of placebo and amisulpride 50 mg and 200 mg, without and with ethanol (0.8 g ⋅kg−1) taken 30 min later. Objective performance tests and self-ratings were done at baseline and 1.5, 3.5 and 6.5 h after drug intake. Memory (immediate and delayed recall) was tested 2 h after dosing. Breath ethanol and the plasma concentrations of amisulpride and prolactin were measured. Three-way ANOVA + Newman-Keul tests were used for statistical analyses; interactions were confirmed by factorial contrast ANOVA. Results: Mean blood ethanol was 0.94, 0.62 and 0.26 g ⋅l−1 at the three test times. It produced significant impairment in all performance tests (symbol digit substitution, simulated driving, body sway, flicker fusion, tapping, nystagmus), reduced both immediate and delayed recall in memory tests, and caused subjective clumsiness, muzziness and mental slowness, mainly between 1.5 to 4.5 h after dosing. Amisulpride, 50 and 200 mg elevated plasma prolactin but had minimal or no effect on performance, attention and memory. The decreases in immediate free recall after the 50 mg dose and in delayed free recall after the 200 mg dose were slight. Amisulpride neither modified blood ethanol concentrations nor enhanced the detrimental effect of ethanol on skilled and cognitive performance; it slightly antagonised ethanol in the digit copying test. Ethanol did not modify the effect of amisulpride on plasma prolactin, and the plasma concentrations of amisulpride were little changed by ethanol. Conclusions: Amisulpride in single oral doses of 50 and 200 mg did not interact significantly with the effects of high, moderate or low concentrations of ethanol on human skilled and cognitive performance. The drugs did interact pharmacokinetically.
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  • 64
    ISSN: 1432-1041
    Keywords: Key words Mefloquine; mefloquine enantiomers ; carboxylic acid metabolite ; blood concentrations ; pharmacokinetics ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To compare concentrations of the separate enantiomers of mefloquine (MQ), total racemic MQ and the carboxylic acid metabolite in different blood fractions at steady state. Setting: Human volunteer laboratory, Unit of Clinical Pharmacology, Karolinska Institute. Volunteers: Ten healthy adult Caucasian volunteers. Methods: Drug concentrations were determined by high-performance liquid chromatography (HPLC). Results: Trough concentrations of the (+)RS enantiomer were higher in venous whole blood than in plasma and serum (mean ratios, 1.41 and 1.38). For the other enantiomer, (−)SR, concentrations were lower in whole blood than in plasma (mean ratio 0.89) and for the metabolite this ratio was 0.5. Conclusion: Stereoselective distribution might be important for antimalarial activity and should be considered when pharmacokinetic studies are performed.
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  • 65
    ISSN: 1432-1041
    Keywords: cyclobarbital ; aminopyrine ; liver disease ; 14CO2 breath test ; barbiturate ; pharmacokinetics ; hepatic drug metabolism ; cirrhosis ; alcoholic liver disease ; viral hepatitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The exhalation of 14CO2 derived from an i.v. tracer dose of [dimethylamine-14C]aminopyrine has been investigated in normal controls and patients. They subsequently ingested 200 mg cyclobarbital calcium in the evening and the decline in the plasma drug level over the following 2 days was measured by thin-layer chromatography. The peak specific activity of exhaled 14CO2 occurred 0.5–2 h after 14C-aminopyrine injection in the absence of liver disease and in non-cirrhotic liver disorders. It was delayed in certain patients with cirrhosis. Compared to 8 medically healthy subjects, 10 patients with acute viral hepatitis, 8 with cirrhosis and 10 with fatty liver exhibited a significantly increased half-life of 14CO2 exhalation. Normal mean values were found in 12 patients with non-cirrhotic alcoholic liver disease and in 14 patients with non-hepatic diseases. The cyclobarbital (CB) half-life was prolonged and the clearance reduced in patients with viral hepatitis, cirrhosis, or alcoholic liver damage as compared to data from 17 control subjects. Due to a larger apparent volume of distribution, patients with fatty liver disease had an increased CB half-life, although its clearance was normal. A close negative correlation was detected between the clearance and the logarithm of the CB level measured 36 h after drug ingestion. The oral CB test evaluated from a single blood sample taken about 36 h after drug administration appears to be a useful indicator of human drug metabolising capacity. Discrimination between patients with and without disordered liver function was similar in the two drug elimination tests.
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  • 66
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    European journal of clinical pharmacology 26 (1984), S. 121-124 
    ISSN: 1432-1041
    Keywords: methotrexate ; psoriasis ; pharmacokinetics ; plasma levels ; urinary excretion ; renal clearance ; tubular absorption
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration and urinary excretion of methotrexate were followed in twelve psoriatic patients after intravenous and oral doses of methotrexate ranging from 7.5 to 30 mg. In six of the patients, a nonlinear relation was found between the fractional amount of methotrexate excreted in the urine and the corresponding area under the plasma concentration-time curve. The methotrexate clearance was found to be increased during the initial high plasma concentration, probably due to saturation of the tubular reabsorption of methotrexate. Considerable interindividual variation was found in the apparent saturation point of the active reabsorption, but up to 500–800 ng/ml first order kinetics still applied. At plasma concentrations below saturation, the renal clearance of methotrexate ranged from 52–102 ml/min (mean±SD, 83±19.4 ml/min).
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  • 67
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    European journal of clinical pharmacology 26 (1984), S. 87-93 
    ISSN: 1432-1041
    Keywords: enprofylline ; pharmacokinetics ; renal elimination ; renal insufficiency ; healthy subjects ; creatinine clearance ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Enprofylline, a new bronchodilating drug, was given i.v. at 1.0 mg/kg to 7 healthy subjects and to 14 patients with differing degrees of chronic renal insufficiency. Plasma and urine concentrations of unchanged drug were followed by HPLC. In the patients the plasma half-life was prolonged and the total and renal clearances were reduced in direct proportion to the degree of renal insufficiency as determined by creatinine clearance. The unbound fraction of enprofylline in plasma increased from 55% in the healthy subjects to 66% in the group of patients with the highest degree of renal impairment. The volume of distribution terms, Vβ and Vss, both tended to decrease with decreasing creatinine clearance. When the volume term calculations were based on the unbound drug level in plasma, this tendency was enhanced. Side-effects were noted in 4 subjects, and to some extent were related to the plasma level of the drug.
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  • 68
    ISSN: 1432-1041
    Keywords: sulphapyridine ; sulphasalazine ; pharmacokinetics ; rectal administration ; oral administration ; plasma levels ; ulcerative colitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Rectal administration of sulphasalazine to patients with ulcerative colitis has recently been shown to have similar therapeutic activity but fewer side effects than oral treatment. The present study is a comparison of the pharmacokinetics of sulphasalazine (SASP) and its metabolite sulphapyridine (SP) after rectal and oral administration of SASP to 6 patients with ulcerative colitis. The areas under the concentration-time curves (AUC) and the maximum concentrations (Cmax) of SASP and SP were significantly lower after rectal than oral administration of SASP (p〈0.05). These findings support the view that the lower frequency of side effects after rectal administration of SASP may result from the lower plasma levels of SASP and SP.
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  • 69
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    European journal of clinical pharmacology 26 (1984), S. 309-313 
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; therapeutic window ; steady state concentration ; pharmacokinetics ; cardiovascular effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonidine was given orally as monotherapy in increasing daily doses from 3.1 to 25.7 µg/kg to patients with essential hypertension (n=6). When a steady state concentration in plasma was reached at each dose level, the blood pressure (BP) and heart rate were measured during a dosage interval. Effect time — plasma concentration data were submitted to nonlinear regression analysis, which showed that the observed BP effects could be dissociated into depressor and pressor components. A window for the antihypertensive effect was established. At a plasma clonidine concentration of 0.65±0.07 ng/ml 50% of the maximal depressor effect was found, and it was only separated by a factor of 2 from the half maximal pure pressor concentration in plasma. No relationship between the change in heart rate and the plasma clonidine was observed. The findings strengthen the importance of close monitoring of clonidine therapy.
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  • 70
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    European journal of clinical pharmacology 26 (1984), S. 381-388 
    ISSN: 1432-1041
    Keywords: midazolam ; hypnotic drug ; benzodiazepine ; pharmacokinetics ; aged patients
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of midazolam, an imidazo-benzodiazepine derivative, have been studied in 13 subjects over the age of 60 years who received the drug intravenously (0.07 mg kg−1) as an induction agent for endoscopy. Two to three days later, 6 of these subjects received 5 mg of midazolam intramuscularly, and another 6 of the subjects received 10 mg of the drug orally. The plasma concentration-time curves were again studied pharmacokinetically. After intravenous dosing, the mean (± SD) elimination half-life (2.14±1.24 h) showed a statistically significant trend to increase with age in the subjects older than 60 years. While the mean (± SD) clearance value (0.30±0.19 l kg−1h−1) tended to fall with age in the elderly subjects, this trend was not statistically significant. Apparent volume of distribution did not appear to be related to advancing age beyond 60 years, and this parameter (mean ± SD) did not differ to a statistically significant extent between the aged subjects (0.77±0.47 l kg−1) and the young subjects studied previously (1.09±0.58 l kg−1). Atropine premedication did not appear to alter the dispositional parameters of the intravenously administered drug. Intramuscularly administered midazolam was absorbed rapidly. Bioavailability appeared incomplete (F=0.59±0.15, mean ± SD), possibly due to saturable elimination of the drug at the higher plasma levels which were obtained after intravenous midazolam. Oral bioavailability, relative to intravenous, was 0.34±0.17, (mean ± SD), with an appreciable but variable lag time (0.74±0.40 h, mean ± SD). Orally, in the dose used, the drug was an inefficient hypnotic with four of the six subjects failing to attain the plasma drug level of 44–50 µg l−1, which appeared to be the approximate threshold for sleep. It is impossible to know whether this failure represents an age related effect on drug absorption, or is a consequence of the upper alimentary tract abnormalities for which the endoscopies were done.
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  • 71
    ISSN: 1432-1041
    Keywords: cefoxitin ; beta-lactam antibiotics ; pharmacokinetics ; serum concentration ; pleural fluid concentration
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefoxitin was studied in 6 healthy volunteers and in 5 patients with a pleural effusion after administration of a single dose of 30 mg/kg i.v. infusion. The serum and pleural fluid concentrations of cefoxitin were determined microbiologically. The elimination half-life of the antibiotic from pleural fluid in all cases was 2–3fold longer than from serum, which shows a difference between the kinetic elimination processes of the antibiotic from the two fluids. The slow elimination of cefoxitin from pleural fluid facilitates its accumulation in this compartment during a multiple dosage regimen.
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  • 72
    ISSN: 1432-1041
    Keywords: cefoperazone ; peritoneal dialysis ; pharmacokinetics ; terminal renal failure ; peritonitis
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefoperazone after i.p. and/or i.v. administration were studied in 12 CAPD patients. After i.v. injection, the plasma half-life was 2.65±0.4 h, the total clearance amounting to 70.1±19.2 ml/min. Peritoneal clearance was calculated to be 6.9±1 ml/min. After peritoneal instillation, the bioavailability was 63.9±5%. After repeated i.p. administration, no accumulation of the drug in the body was observed. Thus, cefoperazone can be safely administered for the treatment of peritonitis in CAPD patients.
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  • 73
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    European journal of clinical pharmacology 26 (1984), S. 651-653 
    ISSN: 1432-1041
    Keywords: prednisolone ; prednisone treatment ; pharmacokinetics ; individual variation ; microsomal enzyme induction
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients on long-term prednisone treatment were studied on two occasions separated by 45 to 325 days. In 10 patients the total body clearance of prednisolone only changed about 10%. In one case a 78.5% decrease was observed after stopping treatment with rifampicin and isoniazide. No association was found between the prednisone dose rate (mg/kg per month), patient age or mean endogenous plasma hydrocortisone level and prednisolone clearance/kg. The results indicate considerable intra-individual consistency of prednisolone kinetics if other conditions are not changed.
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  • 74
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    European journal of clinical pharmacology 26 (1984), S. 749-752 
    ISSN: 1432-1041
    Keywords: dextropropoxyphene ; pharmacokinetics ; half-life ; 3-compartment model ; steady state prediction ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Data from a previously published single dose study of d-propoxyphene 65 mg given i.v. to 8 healthy subjects have been subjected to non linear regression analysis by a curve-fitting program to test the applicability of a 2- and a 3-compartment open model. Analysis of residuals (difference between observed and computed concentrations) revealed similar systematic deviations in all 8 subjects when the 2-compartment model was used (5–10 h negative residuals, after 13 h positive residuals). In contrast, curve-fit by a 3-compartment model (with two parallel peripheral compartments) was good with no systematic deviations. The data show that a terminal monoexponential decline in d-propoxyphene concentrations cannot be expected until 15–30 h after single dose administration, and that the determination of the corresponding half-life is rather inaccurate. Accordingly, precise steady state level predictions may be difficult to obtain from conventional single dose studies with d-propoxyphene.
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  • 75
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    European journal of clinical pharmacology 27 (1984), S. 105-110 
    ISSN: 1432-1041
    Keywords: phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
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  • 76
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    European journal of clinical pharmacology 27 (1984), S. 159-163 
    ISSN: 1432-1041
    Keywords: endralazine ; renal impairment ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of renal impairment on the pharmacokinetics of endralazine was studied in 12 patients; 4 patients on regular haemodialysis therapy (creatinine clearance less than 5 ml/min) and 8 patients with varying degrees of renal impairment (creatinine clearance 11–52 ml/min). Following an oral dose of 10 mg endralazine the mean terminal elimination half-life (βt1/2) in the dialysis sub-group was prolonged at 7.1 h (range 3.3 to 14 h), compared to 3.6 h in the other renal patients (and compared to 2.3 h in hypertensive patients with normal renal function). After one week's therapy with 10 mg B.D. endralazine in the 8 patients with moderate renal impairment there was a significant increase in βt1/2 to 8.6 h but there was no significant change in the area under the drug concentration-time curve and no evidence of drug accumulation. In this study those patients with the poorest renal function had the longest βt1/2 after acute dosing. There was a significant correlation between creatinine clearance and acute βt1/2 but there was considerable variability in individual patients and, even with severe degrees of renal impairment, major dose adjustments do not appear necessary.
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  • 77
    ISSN: 1432-1041
    Keywords: sotalol ; hydrochlorothiazide ; pharmacokinetics ; moderate renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Decreased elimination of a combined formulation of Sotalol (160 mg) and hydrochlorothiazide (25 mg) was found in patients with moderate renal insufficiency. Very slight accumulation of sotalol and hydrochlorothiazide was observed, so it appears unnecessary to reduce the dosage in patients with a creatinine clearance of 30 ml/min or more.
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  • 78
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    European journal of clinical pharmacology 27 (1984), S. 583-587 
    ISSN: 1432-1041
    Keywords: propranolol ; pregnancy ; beta-adrenoceptor antagonist ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Propranolol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32 and 36 weeks gestation and when at least 6 weeks postparum. On both occasions, subjects were given propranolol 120 mg orally or 10 mg intravenously in randomised order with a minimum washout period of 1 week. Propranolol was assayed in plasma by gas-liquid chromatography with electron-capture detection and the pharmacokinetic parameters were investigated. There were no significant alterations in elimination half-life, clearance or apparent volume of distribution per kilogram antenatally compared with postnatally: bioavailability was also unchanged. It is concluded that the disposition of propranolol is not altered during pregnancy.
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  • 79
    ISSN: 1432-1041
    Keywords: Bezitramide ; oral absorption profile ; pharmacokinetics ; male volunteers ; experimental pain ; biliary excretion in rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The oral absorption of bezitramide 5 mg was studied in 7 human volunteers, using a specific radioimmuno-assay which measured both bezitramide and its active metabolite R-4618. A lag time of 0.5–1.0 h and a Cmax of 5.4 ng/ml plasma were found, the latter occurring 2.5–3.5 h after administration. The apparent elimination half-life varied from 11 to 24 h. Less than 0.3% of the dose was excreted unchanged in the urine. High concentrations in the faeces of some individuals indicate incomplete absorption and/or biliary secretion. The analgesic effect, using a standardized superficial electrical stimulation method, reached its maximum between 2.5 and 3.5 h after dosing, in accordance with the absorption phase. The duration of the effect was highly variable. Experiments in rats (n=6,3H-bezitramide 2.5 µg), demonstrated extensive biliary excretion (up to 70% of total radioactivity) and less than 3% of the label was removed by urinary excretion.
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  • 80
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    European journal of clinical pharmacology 26 (1984), S. 341-346 
    ISSN: 1432-1041
    Keywords: cimetidine ; pharmacokinetics ; critically ill patients ; intravenous administration ; dose individualization
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cimetidine disposition was studied after rapid (1 min) intravenous infusion in eight critically ill patients aged between 20 years and 77 years; one patient was studied on two occasions. Cimetidine dose was 300 mg in seven patients and 400 mg in the remaining patient. Arterial plasma cimetidine concentrations at the end of the infusion were very high and ranged from approximately 15–35 mg/l. Pharmacokinetic parameters displayed wide interpatient variability (coefficients of variation of 30–50%) and significant relationships emerged between some of these parameters and certain patient characteristics. Most notable, total systemic plasma clearance of cimetidine was directly related to estimated creatinine clearance (p〈0.01). This relationship might prove to be a useful method of individualizing cimetidine dosage in critically ill patients.
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  • 81
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    European journal of clinical pharmacology 26 (1984), S. 591-593 
    ISSN: 1432-1041
    Keywords: cyclophosphamide ; liver failure ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cyclophosphamide was investigated in 7 patients in severe liver failure. The pharmacokinetic data were compared with those derived from a matched control group of patients with normal liver function. The half-life (t1/2) of cyclophosphamide following intravenous administration in patients with liver failure was 12.5±1.0 h (m±SD), which was significantly longer than in the normal controls in whom it was 7.6±1.4 h (p〈0.001). The mean total body clearance (Clt) was significantly smaller in liver failure at 44.8+8.6l·kg−1 than in the controls in whom it was 63.0±7.6l·kg−1 (p〈0.01). It is concluded that severe liver disease has a significant effect on the disposition of cyclophosphamide, and that it could lead to accumulation of the drug in the body.
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  • 82
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    European journal of clinical pharmacology 26 (1984), S. 647-649 
    ISSN: 1432-1041
    Keywords: tobramycin ; newborn infants ; intrapatient variations ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nineteen newborn infants receiving tobramycin, 2.5 mg/kg every 12 h were studied on two occasions at steady-state during the first week of postnatal age. The two studies were separated by two to four days. Total body clearance of tobramycin averaged 1.15 and 1.14 ml/min/kg (p〉0.05), apparent volume of distribution averaged 0.82 and 0.68 l/kg (p〉0.05), and elimination half-life averaged 8.6 and 7.1 h (p〉0.05), during the first and second study, respectively. When the data were further analyzed based on the birth weight, tobramycin kinetics changed during the second study compared to the first study in very low birth weight infants. In eight infants ⩽1.5 kg birth weight, although total clearance of tobramycin was similar, the average apparent volume of distribution decreased from 1.04 l/kg during the first study to 0.73 l/kg during the second study (p〈0.05) and elimination half-life from 11.1 h during the first study to 8.7 h during the second study (p〈0.05). These data indicate that these infants may require a change in dosing interval with continued tobramycin therapy during the first week of postnatal age. Intrapatient variation in tobramycin kinetics should be considered, in addition to the interpatient variation reported previously, when monitoring the serum concentration to individualize tobramycin therapy in newborn infants ⩽1.5 kg birth weight.
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  • 83
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    European journal of clinical pharmacology 27 (1984), S. 57-59 
    ISSN: 1432-1041
    Keywords: acetaminophen ; pediatric patients ; fever therapy ; accumulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetaminophen serum concentrations were studied in 21 infants and children with fever. The maximum serum concentrations ranged from 9.96 to 19.6 µg/ml after a single dose of 12–14 mg/kg and 13.9 to 40.1 µg/ml after a single dose of 22–27 mg/kg. Ten patients were restudied at steadystate after repeat doses had been given every 4 or 8 h for 1 to 3 days. Total area under the acetaminophen serum concentration-time curve normalized for dose averaged 0.181 (ml/min/kg)−1 after the first dose and 0.202 (ml/min/kg)−1 at steady-state (p〈0.05). Five patients showed a 13 to 44% increase in the AUC; one had a 10% decrease in the AUC; and four had less than 6% change in the AUC. There was no evidence of hepatotoxicity. These data suggest that acetaminophen may accumulate after repeated therapeutic doses in children with fever.
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  • 84
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    European journal of clinical pharmacology 27 (1984), S. 111-114 
    ISSN: 1432-1041
    Keywords: chlorambucil ; chronic lymphocytic leukaemia ; phenylacetic acid mustard ; food intake ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4–7.1) under fasting and 3.3 (range 1.3–7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.
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  • 85
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    European journal of clinical pharmacology 27 (1984), S. 115-117 
    ISSN: 1432-1041
    Keywords: benzodiazepine antagonist ; Ro 15-1788 ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the selective benzodiazepine antagonist Ro 15-1788 has been studied in 6 healthy male volunteers following a single intravenous dose of 2.5 mg. The drug was only slightly bound to plasma proteins (40±8%, mean±SD). A negligible amount (〈0.2% of the dose) of unchanged drug was recovered in urine. Hepatic elimination was rapid, as shown by a short t1/2 of 0.9±0.2 h, and high total plasma and blood clearances of 691±216 ml/min and 716±199 ml/min, respectively. The fast decline of plasma levels from about 60 to 2 ng/ml accounts for the short-lasting reversal of benzodiazepine-induced sedation by Ro 15-1788.
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  • 86
    ISSN: 1432-1041
    Keywords: enprofylline ; healthy subjects ; absorption ; pharmacokinetics ; oral- ; duodenal- ; colonic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Enprofylline, a new potent bronchodilator xanthine drug, was given orally as an aqueous solution to 6 healthy subjects in single doses of 2, 4 and 6 mg/kg. The two lower doses produced plasma concentrations in the range 1–4 mg/l, i.e. in the assumed “therapeutic interval” according to previous animal studies. A high 24 h urine recovery of unchanged drug, with mean values for the three dose levels ranging from 85 to 91% of the given dose, indicated good absorption and little metabolism. The dose-corrected area under the plasma concentration-time curve rose with dose as the latter was increased from 2 to 6 mg/kg. This indicates that the elimination of enprofylline is capacity-limited at high doses. Double peaks in the plasma concentration-time curves at the higher dose levels suggested intermittent and delayed gastric emptying as a possible explanation. This hypothesis was confirmed by studies in 6 other healthy subjects, who received the drug solution by three different routes; by mouth, via a catheter in the duodenum, and rectally via a catheter in the colon. The corresponding time to peak values (mean±SEM) were 32.5±8.7, 13.3±2.5, and 157±23 min.
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  • 87
    ISSN: 1432-1041
    Keywords: kelfiprim ; trimethoprim combination ; sulfamethopyrazine combination ; pharmacokinetics ; renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The combination of trimethoprim (TMP) and sulfamethopyrazine (SMP) has been successfully used to treat chronic urinary tract infections. Since parenchymal involvement associated with renal insufficiency of varying degree is not infrequent in these patients, it was considered important to study the pharmacokinetics of TMP and SMP in a fixed dose combination. Four groups of patients were studied: 1) 4 patients with endogenous creatinine clearance (CLcR) between 80 and 40 ml/min; 2) 3 patients with CLcR between 40 and 10 ml/min; 3) 3 patients on chronic peritoneal dialysis (CAPD); and 4) 3 patients on haemodialysis. A single oral dose of 250 mg TMP and 200 mg SMP was given to each patient. Multiple samples were collected over 9 days and the following pharmacokinetic parameters were calculated: total area under the plasma level curve, slow disposition rate constant β and the corresponding t1/2β, plasma clearance and the apparent volume of distribution. The results show that the two moieties of the TMP-SMP combination behaved differently in uraemic patients as fas as elimination rate was concerned. TMP was eliminated more slowly both in patients with diminished renal function and in those subjected to haemo- or peritoneal dialysis. The reduction in the rate of elimination of TMP was significantly correlated with the degree of renal impairment. The elimination of SMP, however, was not significantly affected by the reduced renal function; indeed a tendency to increase was noted, at least in dialyzed patients. However, as in patients with mild renal insufficiency (CLcR〉40 ml/min) no substantial change in plasma clearance rate need be expected, the TMP-SMP combination could be given to them in the same dose schedule as in people with normal renal function.
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  • 88
    ISSN: 1432-1041
    Keywords: spironolactone ; canrenone ; metabolites ; pharmacokinetics ; single/multiple oral doses ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of canrenone and ‘total metabolites’ after base hydrolysis was studied in eight young volunteers following single and multiple dose oral administration of spironolactone. The plasma levels of canrenone and ‘total metabolites’ were fitted to a two-compartment open model with a first-order absorption process. From our eight normal subjects studied, the harmonic mean of the distributive half-life (t1/2α) of canrenone was found to be 1.66 h, and the harmonic mean of the terminal elimination half-life (t1/2β) to be 22.6 h. Harmonic means of the distributive and elimination half-lives of ‘total metabolites’ after base hydrolysis were 2.48 h and 28.8 h respectively. The accumulation ratio of canrenone was 2.53, whereas that of ‘total metabolites’ was 1.89. Despite the fact that spironolactone has been shown to induce hepatic metabolism of other drugs, no evidence of autoinduction was noted in the present study, as plasma levels of canrenone and ‘total metabolites’ were found to obey a linear two-compartment model with reproducible absorption and disposition after single and multiple doses.
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  • 89
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    European journal of clinical pharmacology 27 (1984), S. 429-433 
    ISSN: 1432-1041
    Keywords: mepindolol ; renal failure ; haemodialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five patients with a creatinine clearance of 14 to 37 ml/min/1.73 m2 were each given an oral dose of 10 mg of the beta-blocker mepindolol sulphate (Corindolan). In addition, two dialysis patients received the same dose either during hemodialysis or on a dialysis-free day. Plasma levels of mepindolol were measured by a sensitive, specific HPLC method. Mepindolol was rapidly absorbed in all the patients. The maximum plasma level of 35±8 ng/ml was reached after 1.4±0.5 h. The half-life of disposition was 4.0±1.5 h. The area under the plasma concentration-time curve was 237±84 ng × h/ml. The data obtained were no different from those found in normal healthy volunteers.
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  • 90
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    European journal of clinical pharmacology 27 (1984), S. 471-475 
    ISSN: 1432-1041
    Keywords: acyclovir ; A515U ; 6-deoxyacyclovir ; pharmacokinetics ; prodrug ; antiviral chemotherapy ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A515U (6-deoxyacyclovir) is an analogue of acyclovir devoid of antiviral activity in vitro but which is well absorbed and undergoes conversion to acyclovir after oral administration to rats. The tolerance and pharmacokinetics of various doses of A515U have been studied in 8 healthy volunteers. Single oral doses of 25, 50, 100, 200 and 400 mg A515U and 400 mg acyclovir for comparison were administered to the volunteers at weekly intervals. Concentrations of the parent drug and acyclovir were determined in plasma and urine. The prodrug was well tolerated and did not cause adverse reactions or changes in haematological or biochemical variables. It was well absorbed and conversion to acyclovir was rapid and extensive at all doses. Plasma concentrations of acyclovir achieved with 50 mg A515U orally were comparable to and less variable than those produced by 400 mg acyclovir. A515U was rapidly cleared with a short plasma elimination half life of approximately 0.5 h. The attainment of high plasma concentrations of acyclovir by oral administration of a prodrug may represent an important advance in antiviral chemotherapy.
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  • 91
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    European journal of clinical pharmacology 27 (1984), S. 619-621 
    ISSN: 1432-1041
    Keywords: biperiden ; pharmacokinetics ; pharmacodynamics ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of biperiden was studied and compared with pharmacodynamics (pupil size, accomodation, self-rating mood scale) in 6 healthy volunteers. A single-blind cross-over design was employed with placebo and biperiden (4 mg as commercially available tablets). After a lag time of 0.5 h, biperiden was rapidly absorbed with a half-life of 0.3 h, plasma peak levels of 5 ng/ml being reached after 1.5 h. Biperiden showed good tissue penetration (distribution half-life 0.6 h; ratio of total to central distribution volume 9.6), the terminal half-life time of plasma concentration was 18 h, and the oral clearance was 146 l/h. The pharmacodynamic maximum lagged behind the plasma peak concentration by 1 (self-rating) to 4 h (accommodation).
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  • 92
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    European journal of clinical pharmacology 49 (1996), S. 477-483 
    ISSN: 1432-1041
    Keywords: Dexamethasone ; Premature neonates ; pharmacokinetics ; bronchopulmonary dysplasia ; infant ; newborn
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Dexamethasone is frequently used in premature neonates with bronchopulmonary dysplasia, however little is known about its disposition in this population. Methods: We evaluated the pharmacokinetics of dexamethasone in 9 premature neonates with a mean gestational age of 27.3 weeks and a postnatal age of 21.8 days. Results: There was a strong relationship between clearance (4.96 ml·min−1·kg−1) and gestational age (r=0.884). Pharmacokinetic parameters were grouped based on a gestational age of less than 27 weeks (Group I) and greater than 27 weeks (Group II). Mean clearance in group I and group II was 1.69 and 7.57 ml·min−1·kg−1, respectively. Mean distribution volume in group I and II was 1.26 and 2.19 l·kg−1, respectively. No significant relationships were noted between the disposition of dexamethasone and ventilator requirements or adverse effects. Conclusion: The pharmacokinetics of dexamethasone in premature neonates was related to gestational age.
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  • 93
    ISSN: 1432-1041
    Keywords: Key words Diprafenone; antiarrhythmics ; bioavailability ; human ; foods ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The present study was done to investigate the effect of food on the bioavailability of diprafenone. Methods: The most important pharmacokinetic parameters (Cmax, t1/2, AUC) and the relative oral availability of a solid oral preparation of racemic diprafenone were investigated when administered to fasting subjects and 10 min after a standard meal, in an open, randomised, crossover trial. Single oral doses of 100 mg were given on two different occasions, at least 1 week apart. The serum concentrations of diprafenone and its hydroxy-metabolite were determined up to 24 hours after administration by a sensitive, specific HPLC method. Fifteen healthy, male volunteers were enrolled in the trial. Their mean height, weight and age were 183 cm, 80 kg and 22 years, respectively. Fourteen volunteers were found to be rapid hydroxylators and one was a slow hydroxylator of debrisoquine. Only data from the rapid hydroxylators were used in the statistical analysis. Results: Food increased the oral bioavailability of diprafenone by approximately 50%. This effect was similar in rapid and in slow hydroxylators. The only slow hydroxylator in this trial had an AUC0–last ratio (with food/fasting) of 1.54. These findings suggest that diprafenone should be administered in a constant temporal relationship to food.
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  • 94
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    European journal of clinical pharmacology 51 (1996), S. 91-93 
    ISSN: 1432-1041
    Keywords: Key words Salbutamol; nebulised ; pharmacokinetics ; COPD ; overnight urinary salbutamol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To evaluate the use of trough plasma salbutamol and overnight urinary salbutamol excretion in the assessment of nebulised salbutamol delivery in patients with chronic obstructive pulmonary disease (COPD). Methods: Twenty in-patients with COPD receiving nebulised salbutamol, age 69.7 years, FEV1 38.1% predicted, were studied on two consecutive days, receiving four 2.5 mg doses of nebulised salbutamol on day 1 and four 5 mg doses of nebulised salbutamol on day 2, the first dose at 8.00 h the last dose at 22.00 h. Salbutamol delivery was assessed after the last dose by trough plasma salbutamol 8.00 h and overnight urinary excretion of salbutamol (22.00–8.00 h). Results: Levels of urinary salbutamol were detectable in all 20 patients at both doses, whereas for plasma salbutamol detectable levels were only found in 16/20 cases at the 2.5 mg dose and in all cases at the 5 mg dose. For overnight urinary salbutamol (μg⋅10 h−1  n = 20) the results were 141 for 2.5 mg and 249 for 5 mg. The dose ratio for urinary salbutamol between 2.5 mg and 5 mg doses was 1.83. Results for plasma salbutamol (ng/ml, n = 16) were 1.58 at 2.5 mg and 2.43 at 5 mg: dose ratio (geometric mean) 1.49. Conclusion: Overnight urinary salbutamol provides a simple and effective measure of nebulised salbutamol delivery in patients with COPD, which would be suitable for studying nebuliser performance and compliance.
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  • 95
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    European journal of clinical pharmacology 26 (1984), S. 223-226 
    ISSN: 1432-1041
    Keywords: diazepam ; metoprolol ; drug combination ; pharmacodynamics ; pharmacokinetics ; drug metabolism ; sedation ; interaction study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 6 normotensive, healthy male volunteers the pharmacodynamic responses (blood pressure, heart rate; sedation index, tracking test, reaction time) to metoprolol (100 mg bid orally), diazepam (0.1 mg/kg intravenously) and to their combination were studied. The pharmacokinetics of diazepam were also compared in a cross-over experiment, with and without pretreatment by the β-adrenoceptor antagonist to evaluate the possibility of a drug interaction. The pharmacodynamic and pharmacokinetic investigations indicated that metoprolol only slightly impaired the elimination of diazepam (18% decrease in total clearance, 25% increase in elimination half-life). The pharmacodynamics of metoprolol (17% decrease in heart rate, 17% decrease in diastolic RR) was not significantly altered by the bolus injection of diazepam. The extent of prolongation in choice reaction time (RT2) induced by diazepam was significantly (p=0.001) more pronounced following the co-administration of metoprolol. However, the results of RT1, the tracking test and the sedation index did not indicate any increased effect due to the β-blocking agent. It is concluded that concomitant treatment with metoprolol and diazepam causes only minor and clinically irrelevant changes in drug metabolism and drug response.
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  • 96
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    European journal of clinical pharmacology 26 (1984), S. 113-119 
    ISSN: 1432-1041
    Keywords: estramustine phosphate ; prostatic cancer ; pharmacokinetics ; metabolism ; estramustine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of estramustine phosphate (EMP) was studied in five prostatic cancer patients given single i.v. and oral doses of EMP in a cross-over study. Plasma and urinary concentrations of parent drug, estramustine, estromustine (the estrone analogue), estradiol and estrone were followed for 32 h. The elimination of intravenous EMP from plasma was biphasic. The mean volumes of distribution were small, being 43 and 108 ml/kg for the central and peripheral compartments, respectively. The plasma clearance was 64 ml/kg/h, and the half-lives of the two phases were 0.16 and 1.27 h. Metabolism was the major route of elimination of EMP. It was readily dephosphorylated and oxidized to yield the cytotoxic metabolites estramustine and estromustine. Estromustine was the main metabolite in plasma. When given orally EMP underwent extensive presystemic dephosphorylation, which started in the gastrointestinal tract. The relative bioavailability of estromustine after administration of EMP-capsules was 44%, which reflects incomplete absorption of EMP rather than first-pass metabolism of estromustine. The terminal half-life of estromustine was 10–20 h, which suggests that EMP might be given once or twice a day.
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  • 97
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    European journal of clinical pharmacology 26 (1984), S. 163-169 
    ISSN: 1432-1041
    Keywords: dopamine ; pharmacokinetics ; pharmacodynamics ; adrenaline plasma level ; noradrenaline plasma level ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and the pharmacodynamic action of dopamine were investigated in 5 healthy subjects. Dopamine was given in different doses (200, 400 and 800 µg/min) by constant intravenous infusion over 90 min. In order to control the influence of the procedure on the measured parameters the subjects also received a similar infusion of saline. Dopamine, noradrenaline and adrenaline levels in plasma were followed for up to 6 h after the infusion, and arterial pressure and heart rate were monitored. Dopamine reached a steady state level within 15 to 30 min after commencement of the infusion; the steady state levels averaged 36.5 µg/l at 200 µg/min, 73.8 µg/l at 400 µg/min and 207 µg/l at 800 µg/min. The corresponding total clearances were 5.8 l/ min, 5.51/min and 3.9 l/min suggesting non-linear kinetics. The kinetics could not be described by compartmental model. Noradrenaline and adrenaline levels were found to be elevated during infusion of dopamine. Noradrenaline had returned to its pretreatment level within 15 to 30 min after cessation of the infusion, whereas the adrenaline level did not return to the pretreatment value within the observation period. Heart rate was increased by the dose of 400 µg/min, and the systolic and mean arterial pressures were elevated, whereas distolic blood pressure remained unchanged. Elevated systolic blood pressure was better correlated with plasma dopamine than with noradrenaline concentration. This finding, in conjunction with the unchanged diastolic blood pressure, indicates that elevation of the systolic blood pressure is a direct rather than an indirect effect of dopamine. The increased heart rate was not correlated with the dopamine level.
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  • 98
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    European journal of clinical pharmacology 26 (1984), S. 261-264 
    ISSN: 1432-1041
    Keywords: indomethacin capsules ; bioequivalence ; volunteers ; pharmacokinetics ; statistical significance ; bioavailability ; comparative bioequivalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Two, separate 6×6 Latin square cross-over bioequivalence studies were performed in adult male volunteers using 10 different indomethacin capsule preparations marketed in India together with the pure drug powder as the standard. The products were evaluated with respect to plasma level at various times up to 8 h following administration of a 50 mg (2 × 25 mg) dose. Plasma samples were analysed by a fluorimetric method. Various pharmacokinetic parameters were calculated according to a two compartment model. Statistical evaluation of the data employed analysis of variance for a cross-over design (ANOVA) and Duncan's multiple range test to ascertain the significance of differences between the products. Of the 10 products studied, two were found to be bioinequivalent.
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  • 99
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    European journal of clinical pharmacology 26 (1984), S. 485-489 
    ISSN: 1432-1041
    Keywords: theophylline ; erythromycin ; interaction ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 11 healthy volunteers the kinetics of theophylline and the plasma levels and the urinary excretion of its metabolites were studied before and after treatment with erythromycin for 10 days. Theophylline was administered as an intravenous bolus injection (280 mg) followed by a constant intravenous infusion (23.8±4.1 mg/h) for 6 hours. The total clearance of theophylline at steady-state (63.4±9.9 vs 63.8±14.4 ml/min, before vs after erythromycin treatment) and the elimination half-life after cessation of the infusion (6.7±2.6 vs 7.5±1.8 h, before vs after treatment) did not change during the treatment with erythromycin. No difference in the formation of metabolites before and after treatment with erythromycin was detected; the findings in urine were 40.4±5.0 vs 42.1±5.4% 1,3-dimethyluric acid, 29.6±4.6 vs 30.1±5.9% 1-methyluric acid and 13.4±3.5 vs 12.5±2.2% 3-methylxanthine before and after erythromycin treatment, respectively. It is concluded that a clinically relevant interaction between erythromycin and theophylline does not occur.
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  • 100
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    European journal of clinical pharmacology 26 (1984), S. 499-503 
    ISSN: 1432-1041
    Keywords: benzodiazepines ; clobazam ; desmethylclobazam ; pharmacokinetics ; sedation ; accumulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen healthy volunteers, aged 19 to 62 years, took a single 20-mg oral dose of clobazam and the serum concentrations of clobazam and desmethylclobazam were measured for the following 7 days. The mean kinetic variables for clobazam were: volume of distribution 1.31/kg, elimination half-life 24 h, total clearance 0.47 ml/min/kg. 13 of the volunteers then took clobazam 5 mg twice daily for 22 consecutive days. Serum concentrations were measured during and after this period. Both clobazam and desmethylclobazam showed slow and extensive accumulation, their steady-state kinetics being entirely consistent with those observed after single doses. Elimination of both compounds after termination of treatment was equally slow. Clinical self-rating of morning sedation indicated a significant increase over baseline in subjective perception of sedation during the treatment period, and this effect persisted into the washout period. However, sedation did not increase in parallel with accumulating levels of clobazam and desmethylclobazam, probably due to functional adaptation or tolerance.
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