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  • Springer  (656)
  • Annual Reviews
  • 1990-1994  (656)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Entomologia experimentalis et applicata 57 (1990), S. 9-16 
    ISSN: 1570-7458
    Keywords: Aphid ; alder ; food quality ; temperature ; ovariole number ; Pterocallis alni
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé P. alni DeGeer (Homopt. Callaphididae) vit sur Alnus glutinosa Gaertner pendant toute l'année. L'aulne étant un arbre fixant l'azote, cette étude a été entreprise pour examiner la croissance et la reproduction de ce puceron sur cet arbre afin d'expliquer les changements de la dynamique de sa population. 6 générations successives estivales ont été élevées dans la nature et en température constante au laboratoire. La qualité de l'aliment a été mesurée chaque semaine par une microkjeldahl analyse des concentrations foliaires en azote soluble. La qualité de l'aliment varie saisonnière, mais ne diminue que de 23%; elle semble n'avoir que peu d'effets sur le puceron, puisque la fécondité dans la nature n'est réduite que pendant une génération. Quand la température est maintenue constante, il n'y a pas de différences entre les performances des différentes générations de pucerons. Ainsi, les changements saisonniers dans la croissance et la reproduction des pucerons sont provoqués par la température et non par la qualité de l'aliment.
    Notes: Abstract Six successive summer generations of the alder aphid (Pterocallis alni (DeGeer) (Homoptera: Callaphididae)) were reared simultaneously in the field and under controlled temperature conditions in the laboratory. The growth and reproduction of each generation were recorded. The available food quality for the aphids was measured by weekly analysis of foliar soluble nitrogen concentrations. Although there was a significant change in leaf soluble nitrogen during the season, the decline was only 23% and this did not appear to have an adverse effect on the performance of this aphid. Instead, the major environmental factor affecting the aphid is temperature. This is evidenced by the facts that when aphids were reared at constant temperatures, there were no differences in generation performance, even though food quality varied seasonally. In addition, all generations of the aphid posess the same number of ovarioles, indicating that there is no pre-programmed anticipation of a seasonal deterioration in food quality in this aphid species.
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  • 2
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    Entomologia experimentalis et applicata 72 (1994), S. 273-279 
    ISSN: 1570-7458
    Keywords: oviposition ; stimulation ; narcosis ; carbon dioxide ; age ; temperature ; photoperiod ; Bombus terrestris
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Four experiments aimed at the stimulation of starting oviposition were carried out with bumblebee queens (Bombus terrestris L.) from colonies belonging to the ecotype of Central Western France and reared in a glasshouse. After mating, queens were narcotized with carbon dioxide, confined singly in small boxes (11×5×4.5 cm) and kept in a dark room at 28–29 °C and 60%–65% r.h. They were fed on a sugar solution and a pollen-syrup mixture. No effects were discernible if the narcosis was applied 20 to 30 days after mating instead of 5 days, nor if the queens were submitted to a 4 to 5 day period at 34°C following narcosis. Survival rates ranged from 65% to 68 %. If the queens were reared under fluorescent tubes (L8∶D16) after narcosis the mean delays to egg-laying were significantly reduced compared to a dark treatment (21 days instead of 39), as was their variability (s.e.=1.6 day instead of 3.1 days). The survival rates were respectively 73% and 67%. Under the same photoperiod (L8∶D16) the CO2 narcosis repeated at a 24h interval had the same efficacy whether its duration was 10 min or 5 min. The delays to egg-laying were respectively 20 days (s.e=1.5) and 25 days (s.e.=4.8) with survival rates close to 73%. Egg-laying could also be induced in non-narcotized queens with a survival rate of 54% and delays to oviposition close to those of queens narcotized 2×10 min.
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  • 3
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    Entomologia experimentalis et applicata 73 (1994), S. 221-229 
    ISSN: 1570-7458
    Keywords: Agaonidae ; host choice ; dispersal ; Ficus ; migration ; Moraceae ; take off ; temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Ficus burtt-davyi, like most other fig species (Ficus, Moraceae), is exclusively pollinated by its own unique species of fig wasp, in this caseElisabethiella baijnathi (Chalcidoidea, Agaonidae). Because fig crop development on any one tree is usually synchronised, the small and short-lived female wasps have to migrate and find other trees bearing figs which are at suitable stage of development for oviposition. However, the likelihood of successful location and subsequent arrival at a new host tree is dependent on distance and the effect of environmental factors such as wind and temperature. This study examines the relationship between ambient temperatures and the timing of fig wasps emergence from their natal figs and the commencement of their dispersal flight. The behaviour of the wasps arriving at figs which were ready to be pollinated was also examined. The female wasps did not appear to distinguish between the figs and other parts of the tree when in flight. However, after landing on the tree their search for figs was more directed as they visited more figs than leaves. Short-range recognition of figs appears to be by contact chemo-reception, but the wasps showed a preference for entering figs which did not already contain a female wasp.
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  • 4
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    Entomologia experimentalis et applicata 72 (1994), S. 25-31 
    ISSN: 1570-7458
    Keywords: diapause induction ; photoperiod ; temperature ; Phyllonorycter blancardella ; spotted tentiform leafminer ; Lepidoptera ; Gracillariidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The role of photoperiod and temperature in the induction of overwintering diapause inPhyllonorycter blancardella (F.) (Lepidoptera: Gracillariidae) was examined in the laboratory and field using leafminers from commercial apple orchards in Ontario, Canada.P. blancardella exhibited a long-day response to photoperiod: long daylengths resulted in uninterrupted development whereas short daylengths induced diapause. The estimated critical photoperiod for diapause induction was L14.25∶D9.75. The larvae of leafminers destined to enter diapause took ca. 3× longer to complete development than the larvae of non-diapausing leafminers. The development prolonging effect of photoperiod decreased with decreasing daylength. Temperature modified the diapause inducing effect of photoperiod. At L14.25∶D9.75, diapause incidence was similar at 15 and 20°C but was lower at 25°C. Photoperiod also altered the normal relationship between development rate and temperature. At L14.25∶D9.75, the duration of larval development of diapausing leafminers was similar at 15, 20 and 25°C. Temperature alone is unlikely to have a role in the induction of diapause because leafminers exposed to natural late summer and fall temperature regimes and L16∶D8 did not enter diapause.
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  • 5
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    Entomologia experimentalis et applicata 72 (1994), S. 125-133 
    ISSN: 1570-7458
    Keywords: growth rate ; consumption rate ; molt ; nutritional ecology ; rutin ; temperature ; thermocycles ; tobacco hornworm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effects of different concentrations of rutin and constant temperature (20 °C) versus alternating temperatures (23∶15 °C) on growth, molting and food utilization efficiencies of third instar tobacco hornworms (Manduca sexta) were determined. Relative consumption rate (RCR) and relative growth rate (RGR) were significantly higher for larvae at the alternating thermal regime compared to those at the constant (representing the average) temperature. With increasing concentrations of rutin, the negative effect of rutin on RCR and RGR increased for the larvae in the alternating thermal regime; however, at the constant temperature, rutin had little effect. The alternating thermal regime promoted synchrony in the timing of spiracle apolysis (the earliest morphological marker of molt). Rutin disrupted that synchrony. I discuss how patterns of host plant resistance may be altered with a decrease, in amplitude of diurnal temperatures (as has been documented recently for temperate regions) through the uncoupling of herbivore performance and allelochemical concentration. I conclude that simultaneous consideration of fluctuating temperatures and allelochemicals is advisable when assessing the effects of temperature and allelochemicals on performance of insect herbivores because interactive effects between temperature and dietary components occur and perhaps are common.
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  • 6
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    Entomologia experimentalis et applicata 73 (1994), S. 127-137 
    ISSN: 1570-7458
    Keywords: Heteroptera ; Anthocoridae ; Orius insidiosus ; Orius tristicolor ; Orius majusculus ; Orius albidipennis ; diapause induction ; termination ; photoperiod ; temperature ; sensitive stages ; biological control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Photoperiodic induction of reproductive diapause at 18°C was investigated in fourOrius [Heteroptera: Anthocoridae] species.Orius insidiosus (Say) displayed a long-day response with a critical photoperiod between L11:D13 and L12:D12. Diapause in this species was terminated rapidly when the temperature and/or the daylength were increased.Orius majusculus (Reuter) also displayed a long-day response. The critical photoperiod fell between L14:D10 and L16:D8. Diapause in this species was not terminated within 14 days when both temperature and daylength were increased. InOrius albidipennis (Reuter) no diapause could be induced at photoperiods varying from L8:D16 to L16:D8. InOrius tristicolor (White) a high proportion of diapause was found at all photoperiods tested. The effect of temperature on photoperiodic induction of diapause was studied inO. insidiosus at L10:D14. Diapause occurred at 18°C, 21°C and 25°C, but not at 30°C. Again, diapause was terminated rapidly after transfer to 25°C/L16:D8. Exposing only the nymphal instars 1–5 to short daylength was not enough to induce diapause in the whole population ofO. majusculus. Orius predatory bugs are used as biocontrol agents against western flower thrips,Frankliniella occidentalis (Pergande) [Thysanoptera: Thripidael, in greenhouses. The consequences of photoperiodic induction of diapause for the success of early season releases ofOrius are discussed.
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  • 7
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    Entomologia experimentalis et applicata 64 (1992), S. 31-36 
    ISSN: 1570-7458
    Keywords: Eurydema rugosa ; adult diapause ; diet ; photoperiod ; temperature ; postdiapause development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract InEurydema rugosa Motschulsky (Heteroptera: Pentatomidae), the type of food supplied (i.e. seeds or leaves of the brown mustard,Brassica juncea Hemsel) and photoperiod, which control the induction of adult diapause, do not play a role in the initiation of reproduction after overwintering. A temperature above 13.2°C was required to start reproduction. After its initiation, however, short-day conditions on seeds induced diapause again in some adults. Although a diet of seeds under long-day conditions, in common with short-day conditions, induced diapause in young adults (Numata & Yamamoto, 1990), it did not reinduce diapause in adults after overwintering. Thus,E. rugosa that had overwintered became sensitive to diapause-inducing photoperiod again but not to dietary factors.
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  • 8
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    Entomologia experimentalis et applicata 68 (1993), S. 127-142 
    ISSN: 1570-7458
    Keywords: tobacco hornworm ; Manduca sexta ; nutritional ecology ; rutin ; temperature ; dietary self-selection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The possibility of avoidance of and dietary self-selection relative to the flavonol rutin was examined for third instarManduca sexta for two thermal regimes and for larvae previously reared on plain or rutin diet. Temperature affected all of the performance indices examined, except efficiency of conversion of digested food. Significant interactive effects between temperature and diet occurred for relative consumption rate, relative growth rate and the food utilization efficiencies. For example, at the warm daytime temperature, relative growth rate prior to head capsule slippage was lower for caterpillars previously reared on rutin diet compared to those reared on plain diet. In contrast, at the cool daytime temperature, the relative growth rates were similar for caterpillars reared on plain diet and on 6 μmoles rutin diet. Consequently, in some treatments (5 of 12), caterpillars with a history of rutin in their diet had lower relative growth rates than those experiencing rutin for the first time. Despite rutin's impact on food utilization indices and negative effect on relative growth rate, the caterpillars did not avoid rutin nor was there evidence of regulation of the intake of rutin. The lack of metabolic feedback is discussed.
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  • 9
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    Entomologia experimentalis et applicata 58 (1991), S. 289-293 
    ISSN: 1570-7458
    Keywords: Spider mites ; Tetranchus urticae ; damage ; feeding ; temperature ; photoperiod
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung Wir untersuchten den Einfluss von Temperatur und Licht auf die Saugtätigkeit von Tetranychus urticae auf Bohnenpflanzen und fanden eine nicht-lineare Beziehung zwischen Temperatur und Saugaktivität. Die Saugintensität stieg bei Temperaturen über 10 °C an bis zum Saugmaximum bei 35 °C und sank dann relativ rasch ab. Permanentes Licht- oder Dunkelregime übte keinen Einfluss auf die Saugleistung aus. Aufgrund der beobachteten Zusammenhänge zwischen Temperatur, Saugintensität und Intensität der Ausbildung der Schadsymptome entwickelten wir ein verbessertes Mass (‘mite-load’) für die Erfassung des Spinnmilbenstresses auf die Wirtspflanze. Die präsentierten Daten zeigen, dass mit der ‘mite-load’ Funktion die Saugschäden von T. urticae präziser erfasst werden können als mit den bisher gebräuchlichen Milbendichten pro Blatt oder Milbentagen.
    Notes: Abstract The influence of temperature and light regime on the feeding intensity of Tetranychus urticae (Koch) (Acari: Tetranychidae) was studied on bean plants. A nonlinear relationship was found between temperature and feeding activity of T. urticae. The feeding intensity increased from 10 °C to 35 °C. At 10 °C there was practically no feeding, whereas at 35 °C maximum feeding occurred. above 35 °C the activity of the mites decreased. No difference could be found in the feeding intensity of mites kept at permanent darkness or permanent light. Based on the observed relationship between temperature and feeding activity and intensity of damage symptoms, respectively, we propose the use of a mite-load function to define the mite stress imposed on the plant.
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  • 10
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    Entomologia experimentalis et applicata 65 (1992), S. 205-214 
    ISSN: 1570-7458
    Keywords: Bird cherry-oat aphid ; Rhopalosiphum padi ; alate development ; crowding ; photoperiod ; plant quality ; temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Experiments indicated that for offspring of apterousRhopalosiphum padi (L.) (Hemiptera: Aphididae), photoperiod and crowding were the most important determinants of wing development whereas crowding and plant quality were more significant for the next generation. Plant quality became increasingly important as temperature increased while crowding became less so. More alates developed on plants previously infested with aphids, indicating that aphid feeding reduced plant quality. High temperature suppressed alatoid production, but could be overcome by crowding. Temperature appeared to influence wing development indirectly rather than directly by acting on the aphid through the plant. Adult weight and potential fecundity were also reduced for aphids which fed on previously infested plants.
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  • 11
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    Entomologia experimentalis et applicata 66 (1993), S. 127-134 
    ISSN: 1570-7458
    Keywords: Ooencyrtus nezarae ; parasitoid ; adult diapause ; rate of oviposition ; photoperiod ; temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Ooencyrtus nezarae Ishii (Hymenoptera: Encyrtidae) was reared on eggs ofRiptortus clavatus (Thunberg) (Heteroptera: Alydidae) at various temperatures under long-day (L16:D8) or short-day (L10:D14) conditions. There was no diapause during egg, larval or pupal stages under any set of conditions examined. However, at 15°C under short-day conditions, vitellogenesis was arrested in all adult females and they entered diapause. At 15°C under long-day conditions, or at 20°C under short-day conditions, some adult females entered diapause. Under the latter set of conditions, the adult females laid eggs but they laid fewer eggs than under long-day conditions, Even at 25°C, under short-day conditions, adult females laid fewer eggs than under long-day conditions, and this low rate of oviposition was attributed to the retarded development of ovaries. Diapause adults reared at 15°C were more resistant to low temperature than nondiapause adults reared at 25°C.
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  • 12
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    Entomologia experimentalis et applicata 70 (1994), S. 27-39 
    ISSN: 1570-7458
    Keywords: almond seed wasp ; Eurytoma amygdali ; diapause termination ; insect dormancy ; temperature ; prolonged diapause ; photoperiod ; Hymenoptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Diapausing larvae ofEurytoma amygdali Enderlein (Hymenoptera, Eurytomidae) were collected in early August and late September. They were subjected to various photoperiod and temperature regimens for up to 20 weeks, then kept at L16:D8 and 19°C for another 14 to 26 weeks for diapause to be terminated and pupation to take place. Photoperiod did not affect diapause completion. It was confirmed that the two morphologically distinct diapause stages have different temperature requirements for their completion. The first diapause stage was completed synchronously at temperatures between 16 and 19°C. A higher temperature of 26°C delayed diapause development. The second stage required lower temperatures between 4 and 10°C. Spontaneous termination of dipause was observed at constant 19°C. When applied to the first diapause stage for 20 weeks, low temperatures made the larvae refractory to subsequent intermediate temperatures. The first stage was thus maintained until a higher temperature of 26°C made the larvae regain their ability to respond to the intermediate temperatures and complete this stage. Larvae grown in Retsou almonds had a higher diapause intensity than larvae grown in Truoito almonds. The results suggest that, in nature, the high temperatures of late summer and early autumn are likely to maintain the first diapause stage. Subsequently, the less warm temperatures of autumn allow the completion of the first stage by late autumn, and the low temperatures of late autumn and of winter allow the completion of the second diapause stage by mid winter.
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  • 13
    ISSN: 1570-7458
    Keywords: Beauveria bassiana ; Leptinotarsa decemlineata ; larval infection ; adult survivor ; fecundity ; egg hatchability ; inoculum dosage ; temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Les effets secondaires de l'hyphomycète entomopathogène, Beauveria bassiana (Bals.) Vuill. sur la fécondité et la fertilité des insectes survivant à l'infection fongique ont été étudiés chez les adultes du doryphore Leptinotarsa decemlineata Say (Coleoptera:Chrysomelidae) issus de larves contaminées en début de 4ème stade. Les insectes maintenus à 22°C ont présenté une réduction de leur potentiel reproductif. Ainsi, suivant la dose d'inoculum fongique, le nombre total d'oeufs pondus par femelle et le nombre moyen d'oeufs par opplaque ont baissé de 20% à 56% et de 18% à 46%, respectivement. En revanche, à 25°C la fécondité des adultes survivants n'a pas été affectée par la maladie. Cette variabilité en fonction des conditions thermiques peut être liée à la diminution de l'effet-dose du champignon sur les larves à 25°C par rapport à 22°C. Par ailleurs, quelles que soient les conditions thermiques (22°C ou 25°C) on ne constate aucun changement significatif de la fertilité des oeufs pondus par les femelles survivantes. Les auteurs concluent que les effets secondaires de B. bassiana sur la fécondité du doryphore dépendent des conditions thermiques et qu'ils pourraient devenir négligeables à des températures élevées en plein champ.
    Notes: Abstract Secondary effects of the entomopathogenic hyphomycete Beauveria bassiana (Bals.) Vuill. were investigated on adults of Leptinotarsa decemlineata Say (Coleoptera:Chrysomelidae) treated as newly moulted 4th-instar larvae. Fecundity and egg hatching were monitored in surviving females mated with surviving males. When reared at 22°C, adult survivors showed a lessening of their reproductive potential during their whole life. According to the fungal inoculum dosage, the reductions of the total number of eggs laid per female and the mean number of eggs per egg mass ranged from 20% to 56% and from 18% to 46%, respectively. In contrast, at 25°C, the fecundity of survivors was not affected by the fungal infection. This variability of the secondary effects of B. bassiana according to temperature conditions might be related to the lower infection level of treated larvae at 25°C. Moreover, at both temperatures, eggs laid by females surviving fungal infection as larvae were as fertile as eggs laid by control insects. It is concluded that secondary effects of B. bassiana on the fecundity of the Colorado Potato Beetle are temperature-dependent and that they could become negligible at high temperatures under field conditions.
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  • 14
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    Entomologia experimentalis et applicata 72 (1994), S. 135-143 
    ISSN: 1570-7458
    Keywords: potassium ; rutin ; temperature ; food utilization efficiencies ; molt ; nutritional ecology ; Manduca sexta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract the simultaneous effects on an insect herbivore (third instar tobacco hornwormManduca sexta (L.): Sphingidae) of temperature (daytime temperatures of 20 °C, 25 °C and 30 °C), a mineral that may play a role in plant defense (potassium) and a common allelochemical (rutin) were examined in a factorial experiment. To manipulate potassium levels, a modified diet with limited plant material was used as the base and KCl and rutin added. Temperature affected efficiency of conversion of ingested food (ECI), efficiency of conversion of digested food (ECD), time to head-capsule slippage, stadium duration, relative consumption rate (RCR) and relative growth rate (RGR) but not food consumed, biomass gained and approximate digestibility (AD). Potassium concentration influenced all of the variables except AD, time to head-capsule slippage (HCS), duration of the stadium and percent of stadium time to HCS. Rutin impacted negatively on all of the variables except food consumed. Compared to larvae on the non-rutin diets, fewer larvae fed rutin survived through molt initiation to ecdysis and fewer successfully completed ecdysis. Temperature and rutin had interactive effects for AD, ECD, RCR, RGR, time to HCS, and percent of stadium required to reach HCS. Rutin and potassium had interactive effects for biomass gained, RCR, ECI, time to HCS, duration of stadium, and percent of stadium required to reach HCS. Comparison of larval responses on an average potassium concentration (3.1%) versus high concentration (6.1%) showed that at the low daytime temperature increasing potassium concentration depressed biomass gained, but at the warmer temperatures potassium concentration had little effect unless rutin was present. In addition, potassium concentration had little impact on ECI unless rutin was present. These results indicate that significant interactive effects occur among temperature, potassium and rutin, and thus suggest that such interactive effects on larval performance may be common under field conditions, which are characterized by varying temperature and different concentrations of minerals and allelochemicals in hostplants.
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  • 15
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    Journal of solution chemistry 19 (1990), S. 1137-1151 
    ISSN: 1572-8927
    Keywords: Ethylbenzene ; excess entalphy ; excess volume ; experimental ; heat capacity ; isobaric expansibility ; isentropic and isothermal compressibility ; liquid mixtures ; mixing function ; n-alkanes ; n-hexadecane ; n-tetradecane ; pressure ; temperature ; theory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Isobaric expansibilities α P and isothermal compressibilities κ T have been determined at 25 and 45°C for binary mixtures of ethylbenzene + n-tetradecane and + n-hexadecane and the corresponding excess functions (∂V E /∂T)P and (∂V E /∂P)T have also been obtained. With these data and supplementary literature values, the following second order mixing properties are also reported at 25°C: κ S E , (∂V E /∂P)T, ΔCV and Δ(ΔγVT). All mixing quantities have been compared with the results obtained at 25°C by using the Prigogine-Flory-Patterson theory of liquid mixtures. The predicted values suggest that the ability of ethylbenzene as a breaker of the pure n-Cn orientations is similar to what we found for toluene and higher than for p-xylene.
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  • 16
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    Journal of solution chemistry 23 (1994), S. 997-1018 
    ISSN: 1572-8927
    Keywords: Conductivity ; aqueous ; sodium chloride ; pressure ; ion association ; temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Electrical conductance measurements of dilute (〈0.1 mol-kg−1) aqueous NaCl solutions were made primarily to quantify the degree of ion association which increases with increasing temperature and decreasing solvent density. These measurements were carried out at temperatures from 100 to 600°C and pressures up to 300 MPa with a modified version of the apparatus used previously in the high temperature study in this laboratory. Particular emphasis was placed on conditions close to the critical temperaturelpressure region of water, i.e., at 5° intervals from 370 to 400°C. The results verify previous findings that the limiting equivalent conductance Ao of NaCl increases linearly with decreasing density from 0.75 to 0.3 g-cm−1 and also with increasing temperature from 100 to 350°C. Above 350°C. Ao is virtually temperature independent. The logarithm of the molal association constant as calculated exclusively from the data≥400°C is represented as a function of temperature (Kelvin) and the logarithm of the density of water (g-cm−3) as follows: $$log K_m = 0.997 - 650.07/T - (10.420 - 2600.5/T)log\rho _w $$ Note that this function also provides a good representation of the log Km values obtained from 350 to 395°C at densities greater than ca. 0.6 g-cm−3. More precise conductance data now available in the literature suggest a systematic error of unknown origin may exist in the data obtained at lower densities in this region. The relevant thermodynamics quantities derived from differentiation of this equation with respect to temperature and pressure are listed in the text.
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  • 17
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    Journal of solution chemistry 20 (1991), S. 805-816 
    ISSN: 1572-8927
    Keywords: Alkanes ; 1-chlorobutane ; compressibilities ; excess volume ; expansibilities ; heat capacities ; heat of mixing ; liquids ; pressure ; temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Isothermal compressibilities KΥ and isobaric thermal expansion coefficients αp have been measured at 25 and 45°C for pure components and the following binary mixtures: 1-chlorobutane+normal alkanes (n-Cn) where n=6, 8, 10, 12, 14 and 16. With these results and other thermodynamic data from literature the next mixing quantities have also been reported: (∂V E/∂T)P, − (∂V)E/∂P)T, K S v , ∂H E/∂P)T, Δ(αpγVT and ΔCv. The obtained results have been compared at 25°C with the calculated values by using the Prigogine-Flory-Patterson theory of liquid mixtures. The theory predicts the excess volume VE and ∂V E/∂P)T values rather well, the C P E quite poorly, while for ∂V E/∂T)P and ∂V E/∂P)T it is only predicted the trend with the chain length of the n-alkane. The last two quantities show deviations between theoretical and experimental, slightly higher in systems with longer n-alkanes than for shorter ones. Our conclusion is that a nonrigid linear molecule, like 1-chlorobutane, has a low ability as a breaker of the pure n-Cn orientation correlations, in between that which we found for toluene and p-xylene and much smaller than for cyclohexane or benzene.
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  • 18
    ISSN: 1572-8927
    Keywords: Phosphate ; protonation ; temperature ; pressure ; calorimetry ; equilibrium constants ; enthalpy and entropy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Flow calorimetry has been used to study the interaction of HPO 4 2− and H2PO 4 − with H+ in water at temperatures of 348.15 and 398.15 K and at pressures of 1.52 and 12.50 MPa. The protonations of HPO 4 2− and H2PO 4 − are exothermic and endothermic, respectively, under these experimental conditions. Under the conditions of this study, the effect of pressure on the enthalpy changes for both reactions is small. Equilibrium constant K, enthalpy change ΔH, and entropy change ΔS values are given for the protonation reactions at each temperature. These values are compared with those reported in the literature. Incorporation into the calculation procedure of reactions involving association between protonated phosphate species to form hydrogen-bonded dimers does not result in better fits of the experimental data.
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  • 19
    ISSN: 1572-879X
    Keywords: EXAFS ; Pt/Al2O3 catalyst ; temperature ; pressure ; carbon deposition ; carbon removal
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    Topics: Chemistry and Pharmacology
    Notes: Abstract EXAFS has been used to follow in situ the structural evolution of a Pt/Al2O3 catalyst during removal of carbon by hydrogenation, after reduction and carbon deposition. After reduction at 350 °C, the total hydrogen pressure was raised to 3 atm. and n-heptane was injected over the sample. EXAFS measurements at the Pt edge were carried out with simultaneous on-line EXAFS analysis of the spectra. After observing the rapid formation of a carbon-platinum bond which is unmodified with time, we stopped the heptane flow, raised the temperature to 450 °C, and maintained hydrogen flow at 3 atm. The disappearance of the platinum-carbon bond during heat treatment in hydrogen was monitored via on-line analysis. No sintering of the metal particles was observed. EXAFS is thus proven to be an efficient tool to study not just structural changes of a catalyst during a hydrocarbon reaction [1], but also to use it as a technique to study other catalytic phenomena as well.
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  • 20
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    Entomologia experimentalis et applicata 60 (1991), S. 143-155 
    ISSN: 1570-7458
    Keywords: Thrips obscuratus ; Thysanoptera ; Thripidae ; New Zealand flower thrips ; rearing ; oviposition rate ; development time ; temperature ; diet ; pollen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The life history of New Zealand flower thrips (Thrips obscuratus (Crawford), Thysanoptera: Thripidae) was studied using a simple laboratory rearing method. The effects of temperature and diet on oviposition rate and development time were examined. Oviposition rate increased with increasing temperature between 10°C and 25°C. Development time for individual instars and for total development decreased with increasing temperature between 10°C and 27°C. Total development time ranged from 50 days at 10°C (female) to 10 days at 27°C (male). The relationship between temperature and development rate was expressed as a straight line such that lower thresholds of development of between 4.2°C and 6.3°C were established for life stages. Adult lifespan increased with decreasing temperature between 10°C and 25°C and females lived longer than males. At 10°C and 25°C females lived for an average of 34 and 3 weeks respectively. Thrips supplied with pollen exhibited highest and sustained levels of egg production in comparison to other diets. Larval mortality was lowest and development time fastest on diets of pollen and sucrose or fruit juice in comparison to other plant tissues. Larval development time was similar on four species of pollen.
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  • 21
    ISSN: 1572-879X
    Keywords: EXAFS ; Pt/Al2O3 catalysts ; chlorine ; temperature ; pressure ; reduction ; deactivation
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    Topics: Chemistry and Pharmacology
    Notes: Abstract EXAFS has been used to follow in situ the structural evolution of a chlorinated and non-chlorinated Pt/Al2O3 catalyst during reduction in the temperature range of 300–500 °C. Smaller metal clusters are formed from the hydrogen reduction of the chlorinated catalyst, in contrast to the larger cluster formed from the non-chlorinated one. At 460 °C, the total hydrogen pressure was raised to 5 atm. and n-heptane was injected over the samples. EXAFS measurements at the Pt edge were carried out while hydrocarbon conversion was monitored with a gas Chromatograph. We observe the rapid formation of a carbon-platinum bond. This is unmodified while turnover rates and selectivities indicate evidence for deactivation. From this structural information supplied by EXAFS, correlated with the data obtained from gas chromatography, we find that our results are consistent with a model proposed by others where deactivation is due to the build-up of a multilayer of carbon.
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  • 22
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    Entomologia experimentalis et applicata 59 (1991), S. 59-66 
    ISSN: 1570-7458
    Keywords: Bruchidae ; adult polymorphism ; temperature ; hygrometric factors ; reproductive quiescence ; population dynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Callosobruchus maculatus (F.) est un Coléoptère Bruchidae tropical qui se développe aux dépens des graines de Vigna unguiculata. Les adultes présentent un polymorphisme; il y a en effet deux formes, la forme voilière et la forme non voilière, distinctes par des critères morphologiques, physiologiques et comportementaux. L'évolution des populations de C. maculatus a été suivie pendant toute la saison sèche et le début de la saison des pluies dans la région de Niamey au Niger (13° LN) à l'intérieur d'un grenier traditionnel. Pendant toute la saison sèche, 6 à 7 générations de C. maculatus de la forme non voilière se succèdent à l'intérieur du grenier. Les adultes de la forme voilière, très actifs, apparaissent surtout au cours de la saison des pluies lorsque la teneur en eau de l'atmosphère et la teneur en eau des graines augmentent. Les études expérimentales réalisées au laboratoire montrent que le polymorphisme imaginal est induit au cours du développement post-embryonnaire et dépend des conditions climatiques dans lesquelles celui-ci a lieu. Le taux d'adultes de la forme voilière est élevé lorsque les larves se développent dans des graines à forte teneur en eau (14 ou 15%). Lorsque la teneur en eau des graines est faible (6 à 7%), il n'y a émergence que d'adultes de la forme non voilière. Lorsque la teneur en eau des graines est comprise entre 12 et 13%, le taux d'adultes de la forme voilière s'accroit et varie avec la durée de la thermophase. A basse température il y a toujours émergence d'adultes de la forme non voilière, quelle que soit la teneur en eau des graines. L'influence de ces deux facteurs abiotiques sur l'induction du polymorphisme imaginal joue probablement un rôle important dans les mécanismes adaptatifs permettant le maintien de cette espèce en zone tropicale.
    Notes: Abstract Callosobruchus maculatus (F.) is a tropical insect (Coleoptera: Bruchidae) that develops in Vigna unguiculata (Walp) seeds. In this beetle, there are two distinct adult forms that differ in their morphology, physiology and behaviour, the flight form and the flightless form. The development of C. maculatus is analyzed in a traditional store in Niger. During the dry season, 6 to 7 generations of the flightless form develop in the store. When the atmospheric water content increases during the rainy season, adults of the flight form appear and escape from the store. Experimental studies have shown that the adult polymorphism is induced during post-embryonic development and depends on prevailing abiotic factors during this period. The proportion of flight from adults is high when larvae develop in moist seeds (14–15% of water content). Under dry conditions (6–7% of water content) only flightless adult forms emerge from the seeds. Temperatures during development also influence adult polymorphism. In thermoperiodic conditions with 12–13% seed water content, the proportion of flight from adults increases with increasing duration of the thermophase. However, at low temperatures, a high proportion of flightless adult forms emerge, regardless of seed water content. The adaptive importance of these two abiotic factors on polymorphism induction is examined in this study.
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    Entomologia experimentalis et applicata 55 (1990), S. 161-168 
    ISSN: 1570-7458
    Keywords: Tephritidae ; Dacus oleae ; olive fruit fly ; ovarian maturation ; olive fruit ; diapause ; photoperiod ; temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé La maturation ovarienne des femelles adultes agées de 7, 22–23 et 28 jours de D. oleae ayant accompli leur développement embryonnaire, larvaire et nymphal en LD 12:12, 19±1°C et maintenues en LD 16:8, 26±1°C, sans accès à des olives, est inhibée. Dans les mêmes conditions, mais avec accès permanent à des olives, 54% des femelles ont des ovocytes mûrs à 7 jours, 87% à 22–23 jours et 100% à 28 jours. Avec des femelles ayant accès à des domes de paraffine, les pourcentages d'individus ayant des ovocytes mûrs sont intermédiaires entre ceux des deux situations précédentes. Dans les conditions cidessus défavorables à la maturation ovarienne, 50% des femelles de 28 jours ont des ovocytes mûrs si elles sont en présence d'olives durant leur première semaine de vie imaginale et 91% si elles sont en présence la 4éme semaine. Les pourcentages respectifs concernant les femelles pourvues de dômes de paraffine sont encore intermédiaires entre ceux des femelles avec olives et ceux de femelles privées de tout substrat. La présence d'olives a aussi un effet fortement positif sur la maturation ovarienne de femelles ayant accompli leur développement pre-imaginal et maintenues aussi à l'etat adulte en conditions LD 16:8, 26±1°C, favorisant la maturation ovarienne. L'accès à des dômes de paraffine a, là encore, un effet intermédiaire. On conclut par conséquent que la non maturation ovarienne des femelles de D. oleae qui est causée par une photopériode à jour court pendant la vie pre-imaginale accompagné par une photopériode à jour long et une augmentation de la température pendant la vie imaginale persiste au moins jusqu'à la fin de la quatrième semaine de la vie imaginale en absence d'olives, mais ne se produit pas si on met les femelles adultes en présence d'olives.
    Notes: Abstract Ovarian maturation was prevented in 7-, 22-, 23- and 28-day-old females of Dacus oleae (Gmelin) (Diptera: Tephritidae), developed in the pre-imaginal stages at LD 12:12, 19±1°C and kept as adults at LD 16:8, 26±1°C without access to olive fruits. In females of the above ages having continuous access to olive fruits and held under the same photoperiod and temperature conditions, 54, 87 and 100%, respectively, had mature oocytes. When the females had access to domes of paraffin wax, the percentages of females with mature oocytes were intermediate between those with and those without access to olive fruits. Under the above photoperiod and temperature conditions unfavorable for maturation, 50% of 4-week-old females had mature oocytes if exposed for one week to olive fruits during their first week and 91% if exposed during their 4th week of adult life. The respective percentages with wax domes in the cages were again intermediate between those with olives and those without olives or wax domes. The presence of olive fruits had also a strong positive effect on the ovarian maturation of females which developed from egg through the adult stage at LD 16:8, 26±1°C, a condition favoring ovarian maturation. Access to wax domes had again an intermediate effect on maturation. It is concluded therefore that the lack of ovarian maturation of D. oleae females which is observed under a short photophase during the pre-imaginal stages if followed by a long photophase and an increase of temperature during the adult stage, continues at least till the end of the 4th week of adult life in the absence of olive fruits but is averted when such fruits are offered to the adult flies.
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  • 24
    ISSN: 1573-0832
    Keywords: Fusarium crookwellense ; temperature ; zearalenone ; a-zearalenol ; nivalenol ; mycotoxins
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    Topics: Biology , Medicine
    Notes: Abstract After 6 weeks incubation on rice 2 strains of Fusarium crookwellense produced more zearalenone (6060–5010 mg/kg dry wt of culture) at ambient temperature (16–29°C) in daylight than at ambient temperature (18–23 °C) in darkness or at controlled temperatures of 11 °C, 20 °C or 25 °C in darkness. Yields at 25 °C were low. Incubation at 11 °C during the second 3 weeks incubation increased yields only when preliminary incubation had been at 25 °C. After 6 weeks incubation at controlled temperatures in darkness, 4 strains produced most zearalenone at 20 °C (2460-21 360 mg/kg), 1 strain at 11 °C (6570 mg/kg). Yields at a temperature oscillating daily from 10–20 °C were less than at 15 °C. One of the 5 strains produced appreciable amounts of a-zearalenol (1645 mg/kg at 20°C) and 2 of nivalenol (340 and 499 mg/kg at 20 °C).
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    Nutrient cycling in agroecosystems 23 (1990), S. 97-103 
    ISSN: 1573-0867
    Keywords: Carbon ; mineralization ; nitrogen ; organic fertilizer ; temperature
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The C and N mineralization characteristics of two organic N fertilizers were determined in a soil-less incubation system at three temperature regimes. Protox (derived from activated sewage sludge) initially degraded more rapidly by microbial action compared with dried blood. However, dried blood released more CO2-C and inorganic N towards the end of the incubation periods. The rate of microbial degradation increased with temperature. Mineralization characteristics of protein-based N sources are discussed in relation to organic N nutrition of vegetable crops.
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    Natural hazards 9 (1994), S. 5-16 
    ISSN: 1573-0840
    Keywords: Fourier transform ; maximum entropy spectral analysis ; precipitation ; temperature ; climatic change
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    Topics: Energy, Environment Protection, Nuclear Power Engineering , Geography , Geosciences
    Notes: Abstract In the present work, a precipitation and temperature series from Barcelona (Spain) are analysed in order to detect the possible existence of climatic changes or cycles. The analysis is carried out both from the temporal and spectral standpoints. The techniques used range from the classical periodogram and Blackman-Tukey method through to the Maximum Entropy method. The results do not show the existence of climatic cycles, though they do show a clear tendency toward increased precipitation and decreased temperature, since the last years of series.
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    Landscape ecology 6 (1991), S. 15-27 
    ISSN: 1572-9761
    Keywords: Climate ; microclimate ; energy balance ; dunes ; dune formation ; wind ; temperature ; precipitation ; evaporation
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    Topics: Biology
    Notes: Abstract Extremely important to the climate in any region are the radiation balance and the exchange processes of heat, water vapour and momentum. Most climatological parameters (e.g. temperature, humidity, wind speed, cloudiness and precipitation) are the direct or indirect result of the radiation balance and these exchange processes. The weather of the West European coast from Tarifa (Spain) to Skagen (Denmark) is especially suitable for the formation of dunes. Often a wind is blowing, varying widely in force and direction. The conditions are optimal for the formation of high and wide dune complexes, given a large supply of sand by the sea. The annual precipitation surplus is considerable for most of this coast. This favours the establishment of vegetation, and thereby it enhances dune formation. The short distance to the land-sea border causes strong gradients in several climatological parameters. These gradients lead to mesoscale effects, such as land-sea breezes and coastal fronts. The varying vegetation cover and the presence of slopes in all directions induce a strongly varying microclimate. However, this microclimate is not unique to the coastal dunes. Unique is the interaction with the wide range of ambient weather, which is inherent to the coast. It is not possible to be conclusive about the effects of climatic change on coastal dunes because climate models are not yet able to predict the changes adequately and because these models supply information on the expected mean climate, but not on the actual weather.
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    Pure and applied geophysics 141 (1993), S. 487-495 
    ISSN: 1420-9136
    Keywords: Pressure ; temperature ; hydrothermal ; H2O ; equation of state ; diamond anvil cell
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    Topics: Geosciences , Physics
    Notes: Abstract The new hydrothermal diamond anvil cell (HDAC) has been designed for optical microscopy and X-ray diffraction at pressures up to 10 GPa and temperatures between −190°C and 1200°C. Laser light reffected from the top and bottom anvil faces and the top and bottom solid sample faces produce interference fringes that provide a very sensitive means of monitoring the volume of sample chamber and for observing volume and refractive index changes in solid samples due to transitions and reactions. Synchrotron radiation has been used to make X-ray diffraction patterns of samples under hydrothermal conditions. Individual heaters and individual thermocouples provide temperature control with an accuracy of ±0.5°C. Liquid nitrogen directly introduced into the HDAC has been used to reduce the sample temperature to −190°C. The α-β phase boundary of quartz has been used to calculate the transition pressures from measured transition temperatures. With this method we have redetermined 5 isochores of H2O up to 850°C and 1.2 GPa at which the solution rate of the quartz became so rapid that the quartz dissolved completely before the α-β transition could be observed. When silica solutions were cooled, opal spherules and rods formed.
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  • 29
    ISSN: 1420-9136
    Keywords: Pressure ; temperature ; stress ; measurement ; acoustic emissions ; deformation ; techniques
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    Topics: Geosciences , Physics
    Notes: Abstract New and improved techniques and apparatus for testing the mechanical properties of materials at high presures and temperatures are described. These include an improved Griggs-type deformation apparatus designed to operate to 5 GPa and associated servo-controlled hydraulic drive and electronics, the design of hydrostatic (molten alkali halide mixtures) pressure assemblies to measure flow stresses as low as a few MPa, the characterization of temperature gradients and friction in such assemblies, measurement of the melting curve of an alkali halide mixture used as a confining pressure medium, and the measurement of acoustic emissions.
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    Insectes sociaux 41 (1994), S. 401-410 
    ISSN: 1420-9098
    Keywords: Nest structure ; temperature ; brood movement
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    Topics: Biology
    Notes: Summary The structure and thermal environment produced by the nest cones of the western harvester ant,Pogonomyrmex occidentalis, are investigated. The nest cone is oriented so that the longest slope faces towards the southeast ad the nest entrance faces the southeast. The temperature of the soil was monitored at thirty-six locations within the nest in order to measure the daily temperature change as a function of depth, aspect and radial distance from the center of peak of the cone. The occupancy of the nest cone by workers and by brood was assessed by core samples taken at different times of day in different portions of the cone. The brood are only present during the midmorning sample and are present in greatest numbers on the eastern side of the cone. The adult workers are present in the cone in highest numbers during the midmorning, virtually absent from the cone during mid-afternoon and returning in smaller numbers at dusk, apparently spending the night near the surface on the eastern side of the mound. The eastern and southern portions of the cone are occupied most frequently while the western side of the cone is nearly vacant. The nest cone is an adaptation which magnifies the amplitude of daily temperature fluctation. By moving to appropriate areas of the nest cone, the ants can take advantage of the increased range of temperature.
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    Insectes sociaux 40 (1993), S. 169-180 
    ISSN: 1420-9098
    Keywords: Halictidae ; sociality ; demography ; photoperiod ; temperature
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    Topics: Biology
    Notes: Summary Several years' observations of population of a primitively social halictine bee,Halictus rubicundus, revealed the following: (1) there is a correlation between ambient temperatures during the spring provisioning phase and the sex ratio of the resulting brood, such that warmer temperatures are associated with an increase in male bias; (2) over the course of the season, the degree of male bias of eggs laid appears to correspond with photoperiod; and (3) increasing male bias in the first brood is associated with decreasing proportions of social colonies formed in the population, and this effect may be accentuated by small population size. These phenomena suggest that abiotic environmental conditions at the time of brood production may profoundly influence the demography of this population, and that the demography in turn determines the degree to which sociality is expressed. These findings are related to hypotheses dealing with caste determination in temperate halictine bees, viewed in the context of the evolution and maintenance of sociality, and it is proposed that these phenomena reveal a mechanism by which social behavior (the occurrence of a “worker” caste, in particular) is facultatively “fine-tuned” to suit the characteristics of the environment.
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  • 32
    ISSN: 1420-9098
    Keywords: Formica exsectoides ; nests ; colony cycle ; temperature ; brood ; reproductives
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    Topics: Biology
    Notes: Summary The nest structure and colony cycle of a population of Allegheny mound ants,Formica exsectoides, were examined in central Michigan. The dispersion pattern of mounds was random. Nest structure and presence of brood were primarily determined by excavation of twenty-three nests over three intervals from June through September. Additional excavations of five nests in 1990 and ten nests in 1991 provided further details on nest structure and colony cycle. Most galleries occurred within the mound and upper 30 cm of soil, but some activity reached depths of 100 to 270 cm. Depth of nests showed little correlation with external measurements of height and diameter. Immature stages were recovered from two strata: the upper 20 cm of nest and mound and the lowest nest depths. Alate sexual forms were found in or near the mound in July, and numerous dealate queens were collected in September from peripheral galleries near the soil surface.
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    Pure and applied geophysics 133 (1990), S. 251-267 
    ISSN: 1420-9136
    Keywords: Heat flow ; sediments ; temperature ; gradients ; conductivity ; industrial data ; scientific data ; hydrodynamics
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    Topics: Geosciences , Physics
    Notes: Abstract Temperature, temperature gradient and heat flow, derived from four wells in the Western Canada Sedimentary Basin have been compared with similar quantities derived from maps constructed from industrial data. Individual industrial temperature data may differ from the high-resolution temperature log by up to 30 K, but linear regression of the collected data agrees within 10 K at all points observed. Some evidence suggests that measured conductivities, using drill-cuttings, are biased toward average values. Derived heat flows show agreement of heat flow within 10% within the Mesozoic section. In the Paleozoic section differences are greater, and more varied, with insufficient data for general conclusions. Both styles of measurement provide opportunities for interpretation, each contributing to thermal analysis of sedimentary basins.
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    Aquatic sciences 54 (1992), S. 37-57 
    ISSN: 1420-9055
    Keywords: Chile ; monomictic lakes ; temperature ; mixing ; heat budget ; stratification
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    Topics: Biology
    Notes: Abstract Temperature profiles in summer (February/March 1990) were measured in 24 lakes along a latitudinal transect from central Chile (32° S) to Patagonia (47° S), and on Easter Island (27° S). The lakes of the temperature zone, between 47° S and 38° S, are warm monomictic with surface and deep-water temperatures ranging from 12 °C to 21 °C and from 5.5 °C to 10 °C respectively. The heat content per unit area in midsummer was found to vary with lake area. The local stability of stratification (N 2) varied by more than two orders of magnitude, declining with increasing latitude, altitude, and depth. The lakes can be classified according to morphometric and temperature characteristics, mixing depth, stability of stratification and glacial turbidity. Lago General Carrera (463 m) was found to be almost as deep as Lago Nahuel Huapi (464 m), which is considered to be the deepest lake in South America.
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    Cellular and molecular life sciences 48 (1992), S. 904-906 
    ISSN: 1420-9071
    Keywords: Barnyard grass ; Echinochloa crus-galli ; oxygen deficiency ; seed dormancy ; soil seed bank ; stratification ; temperature
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    Topics: Biology , Medicine
    Notes: Abstract At 25°C, secondary dormancy was induced in seeds ofE. crus-galli exposed for 100 days to oxygen deficiency. By contrast, hypoxia did not induce dormancy at 15°C or prevent dormancy termination at 7°C. Secondary dormancy was terminated after 2 months stratification at 7°C. Oxygen deficiency may increase the proportion of dormant seeds in the soil, and affect the dynamics of the barnyard-grass soil seed bank.
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    European journal of clinical pharmacology 42 (1992), S. 101-105 
    ISSN: 1432-1041
    Keywords: Rufloxacin ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma and urine kinetics of rufloxacin were assessed in healthy volunteers after single (100, 200, 400 and 800 mg) and multiple (300 mg followed by 150 mg daily, Group 1, and 400 mg followed by 200 mg daily, Group 2) oral doses. The kinetics of a single oral dose of 800 mg was assessed in fasting and non-fasting subjects to assess the influence of food intake on drug absorption. The AUCs were 134, 266 and 375 μg · h · ml−1 after 100, 200 and 400 mg, respectively. The AUC after 800 mg p. o. was 715 μg · h · ml −1 in fasting subjects and 614 μg · h · ml−1 in non-fasting subjects. The parameters of the model and the mean renal clearance values indicated some departure from linearity in rufloxacin kinetics. After multiple doses the plasma drug levels during the 6th treatment day were similar to those after the first dose in Group 1 and were about 30–40% higher after the first dose in Group 2. The half-lives after the last dose were much shorter than those estimated in the single dose studies (33–36 h and 50–80 h, respectively).
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    European journal of clinical pharmacology 42 (1992), S. 535-538 
    ISSN: 1432-1041
    Keywords: Meropenem ; Carbapenem ; pharmacokinetics ; uraemia ; haemodialysis
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 24 or 48 h. Meropenem concentrations in plasma and urine were measured by a microbiological assay. The mean peak plasma concentration of meropenem ranged from 28 to 40 μg·ml−1 and was not affected by the degree of renal impairment. The terminal half-life of meropenem was approximately 1 h in subjects with normal kidney function and it was proportionately increased as renal function decreased. A significant linear relationship between total body clearance and creatinine clearance as well as between renal clearance and creatinine clearance was observed. The mean apparent volume of distribution at steady state was not significantly altered in uraemic patients. The mean cumulative urinary recovery of meropenem in healthy volunteers was 77% of the administered dose and it was significantly decreased in patients with renal impairment. Haemodialysis shortened the elimination half-life, from 9.7 h during the predialysis period to 1.4 h during the dialysis period. The dose of meropenem should be reduced in relation to the decrease in creatinine clearance.
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    European journal of clinical pharmacology 42 (1992), S. 559-560 
    ISSN: 1432-1041
    Keywords: Mefloquine ; Thai subjects ; pharmacokinetics ; Primaquine ; drug interaction ; adverse effects
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    Topics: Chemistry and Pharmacology , Medicine
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    European journal of clinical pharmacology 39 (1990), S. 395-397 
    ISSN: 1432-1041
    Keywords: atropine ; exercise ; pharmacokinetics ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven healthy males (19–32 y) underwent each of four separate conditions in a repeated measures design. Five of these subjects underwent an additional trial. In four of five trials subjects received 2.0 mg atropine sulfate intramuscularly in the anterolateral portion of the left thigh: at rest (T1); following completion of a single exercise (Ex) bout (T2), (Each bout consisted of 25 min of stationary cycling at 40% VO2 max with 5 min of seated rest), prior to three Ex bouts (T3) and following one and prior to three Ex bouts (T5). Trial 4 (T4) was the same as T3 with the substitution of a saline placebo. Serum samples were collected over a 12 h period and atropine concentration was determined by RIA. Ex trials were compared to T1. Ex prior to atropine (T2) significantly decreased the mean volume of distribution (Vz, 278 vs 2321). Ex in T3 significantly decreased the serum half life (t1/2, 4.2 vs 3.5 h), Vz (278 vs 1981), and clearance (CL, 763 vs 638 ml·min−1) and significantly increased the peak concentration (Cp, 6.7 vs 12.3 ng·ml−1) and area under the curve (AUC, 44.1 vs 53.1 ng·ml−1). In T5, Ex significantly decreased the t1/2 (3.4 h), Vz (182 l) and CL (575 ml·min−1) and significantly increased the absorption rate constant (ka, 0.482 vs 1.1 min−1), elimination rate constant (ke, 0.0012 vs 0.0015 min−1), Cp (14 ng·ml−1) and AUC (53.3 ng·h·ml−1). These results demonstrate that moderate Ex either prior to and/or immediately following drug administration has the capacity to significantly modify atropine pharmacokinetics.
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  • 40
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    European journal of clinical pharmacology 42 (1992), S. 689-691 
    ISSN: 1432-1041
    Keywords: Diphemanil methylsulphate ; pharmacokinetics ; healthy subjects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of oral diphemanil methylsulphate have been evaluated in six healthy male volunteers. Absorption of the drug was slow (tmax=2 to 4 h), the mean half-life was 8.35 h, and the amount of the drug recovered in urine within 48 h ranged from 0.6 to 7.4% of the administered dose. The results suggest low bioavailability, assuming that the drug is poorly metabolized.
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  • 41
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    European journal of clinical pharmacology 42 (1992), S. 693-694 
    ISSN: 1432-1041
    Keywords: Loperamide ; loperamide oxide ; diarrhoea ; pharmacokinetics ; dose-proportionality
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of loperamide, after oral administration of increasing doses (1 to 16 mg) of loperamide oxide, has been investigated in 10 healthy male volunteers, using a randomised cross-over design. Comparison of the maximum plasma loperamide concentration and AUC demonstrated that the bioavailability of loperamide was proportional to the dose of loperamide oxide administered.
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  • 42
    ISSN: 1432-1041
    Keywords: Alpidem ; Anxiolytics ; pharmacokinetics ; tolerance ; metabolites ; sedation ; adverse events
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, placebo-controlled, crossover experiment in 21 healthy male volunteers, aged 19 to 27 y, the pharmacokinetics and tolerance of the new anxiolytic drug alpidem (SL80.0342) and its three major metabolites were studied after single doses of 25, 50, 100 and 200 mg. Plasma concentrations of alpidem (in 20 subjects) and metabolites (in 6 subjects) were measured by HPLC over a period of 54 h after dosing. Cmax, tmax and AUC(0–54) and, when possible, t1/2 were determined for alpidem and metabolites and the dose linearity of the parameters was investigated. The time to peak of alpidem was dose independent in most subjects and was short (1–4 h); the mean values at the four dosing levels were 1.9, 1.7, 1.6 and 1.8 h. The peak concentration increased with the dose, the mean values being 17, 34, 88 and 115 ng · ml−1, respectively. In 50% of the subjects cmax tended to stabilize between the 100 and 200 mg dose. Dose linearity was also present for the AUC, which plateaued between the 100 and 200 mg dose in only 3 out of 20 subjects; the mean AUC was 119, 281, 669 and 1117 ng · ml−1 · h, respectively. The apparent half-life of elimination appeared to be dose independent, mean values at the increasing dosing levels being 18.7, 19.9, 18,1 and 17.9 h. A similar relationship between the kinetics parameters and dose of the alpidem was observed for the metabolites SL83.0912, SL80.0522 and SL83.0725. The formation of metabolites was not saturated as their AUCs relative to corresponding alpidem AUCs were not dose related. Thus the kinetics of alpidem and its three major metabolites were linear after doses of 25 to 200 mg. The drug was well tolerated by most of the subjects. Sedation and dizziness occurred mainly after the 100 and 200 mg doses.
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  • 43
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    European journal of clinical pharmacology 43 (1992), S. 67-75 
    ISSN: 1432-1041
    Keywords: Morphine ; Patient-controlled analgesia ; opioids ; pharmacokinetics ; bolus-elimination-transfer ; computer-assisted continuous infusion
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bone marrow transplant patients having severe, prolonged oral mucositis pain (expected to last for one to three weeks) used a computer-controlled infusion system to self-administer morphine for pain control. Individual patient pharmacokinetic information, derived from a pretreatment bolus morphine dose, was used in a new bolus-elimination transfer algorithm to produce rapid adjustments of steady plasma morphine concentrations when the patient requested more or less drug. We evaluated the performance characteristics (bias and precision) of this pharmacokinetically based patient-controlled analgesic infusion system (PKPCA) in a group of 15 cancer patients over six to 14 days. Although we found a three- to fivefold pharmaco-kinetic variability in the tailoring morphine dose data, the PKPCA system was free of systematic bias (insignificant overall prediction error) during the patient-controlled infusions in this study population. The absolute prediction error was 19.9% for the group on the first study day and 25.6% over the entire study period (aggregate results; 6–14 days of continuous use). Two-thirds of the patients exhibited no bias throughout the study period, and individual bias in the others was symmetrically distributed (three patients with underpredictions and two overpredicted). Magnitude of prediction error during the patient-controlled morphine infusions was not related to the magnitude of pharmacokinetic deviation of individual subjects from group parameters. Our results indicate that this PKPCA system provides accurate control of plasma morphine concentration when used by patients to self-administer opioid for prolonged pain relief continuously over 1 to 2 weeks. Use of individual pharmacokinetic information, instead of population parameters, may account for superior performance characteristic of this computer-assisted continuous drug infusion system.
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  • 44
    ISSN: 1432-1041
    Keywords: Indomethacin ; steady-state ; pharmacokinetics ; elderly
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady-state pharmacokinetic profile of indomethacin was examined in twelve healthy volunteers (4 m, 8 f; 20–34 y) and in 12 elderly subjects (7 m, 5 f; 70–88 y). Two formulations of indomethacin were examined, providing duplicate data for each subject group. The subjects received each formulation of indomethacin (25 mg tid) for 6 days in a single blind crossover fashion. On day 7, after an overnight fast, a final 25 mg dose of indomethacin was given and plasma concentrations measured over the following 12 h. Kinetic parameters Cpmin, tmx and AUC (0–12 h) were determined. There were no differences in the pharmacokinetic parameters between young and elderly subjects or between data for the two formulations of indomethacin. AUC values (μg · ml−1 · h), for example, for the two formulations in the young subjects were 5.85 and 6.85 while the values for the elderly subjects were 6.55 and 6.50 respectively. When each treatment period was considered independently there was a significant difference between young and elderly subjects with regard to compliance. The rates of non compliance (over and under compliance) using a capsule count technique were, however, low with a mean maximum value of 5.8% being recorded for the elderly subjects.
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  • 45
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    European journal of clinical pharmacology 41 (1991), S. 449-452 
    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; Caffeine ; pharmacokinetics ; P-450 mono-oxygenase
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Diabetes may alter the pharmacokinetics of aminopyrine and antipyrine, which are used to assess liver function. Caffeine has recently been used to test liver function, but the effect of diabetes on caffeine kinetics is not known. The kinetics of caffeine has been examined in patients with decompensated Type I and Type II diabetes and in two age- and sex-matched control groups. In both types of diabetes the apparent caffeine clearance, half-life, and apparent volume of distribution were similar to controls. It is concluded that decompensated diabetes does not influence the cytochrome P-448 mono-oxygenase system responsible for caffeine metabolism.
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  • 46
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    European journal of clinical pharmacology 42 (1992), S. 231-233 
    ISSN: 1432-1041
    Keywords: Isradipine ; Haemodialysis ; pharmacokinetics ; dialysability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of isradipine, a calcium-channel blocker, have been studied in eight patients on chronic haemodialysis. A single oral dose of 5 mg was administered on both a non-haemodialysis and a haemodialysis day and the plasma concentrations of isradipine were analyzed. The mean cmax, tmax, AUC, and t1/2 in plasma on the non-haemodialysis day were 5.2 ng·ml−1, 1.4 h, 23.8 ng·h·ml−1, and 3.1 h, respectively. The dialysis clearance of isradipine was negligible (5.0 ml·min−1). The t1/2 values during haemodialysis were not significantly different from those observed during the same period post dose on the non-haemodialysis day. The study demonstrates that supplemental doses of isradipine are not necessary in these patients since isradipine is not significantly removed by haemodialysis.
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  • 47
    ISSN: 1432-1041
    Keywords: Liver cirrhosis ; Spirapril ; ACE inhibitor ; pharmacokinetics ; haemodynamic effects ; liver function tests
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensinconverting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n=10), in patients with chronic, non-cirrhotic liver disease (n=8) and in a control group of healthy subjects (n=16). The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 μg·h·l−1, 923 μg·h·l−1 and 1300 μg·h·l−1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively. Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h−1 in patients vs. 2.00 h−1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls. Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients.
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  • 48
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    European journal of clinical pharmacology 40 (1991), S. 593-597 
    ISSN: 1432-1041
    Keywords: Dopamine ; Newborns ; critically ill patients ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5–20 μg · kg−1 · min−1, for presumed or proven sepsis and hypotensive shock. Steady-state concentrations of dopamine ranged from 0.013–0.3 μg/ml. Total body clearance averaged 115 ml · kg−1 · min−1. The apparent volume of distribution and elimination half life averaged 1.8 1 · kg−1 and 6.9 min, respectively. No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants.
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  • 49
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    European journal of clinical pharmacology 40 (1991), S. 619-624 
    ISSN: 1432-1041
    Keywords: Inulin ; pharmacokinetics ; half life ; distribution ; concentration-dependent clearance ; healthy subjects ; chronic renal failure
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of inulin was studied in 30 healthy male and 10 healthy female volunteers, and 10 patients with stable chronic renal failure (mean creatinine clearance 45 ml·min−1) following intravenous infusion of 70 mg·kg−1 over 5 min. Plasma concentrations fell rapidly initially but the rate of decline decreased continuously over 8 h and a linear terminal elimination phase could not be identified. Inulin was excreted rapidly by the subjects with normal renal function and 97.3% of the dose was recovered in the urine in 8 h. There was a progressive highly significant fall in the renal clearance of inulin after 2 h as plasma concentrations fell below about 150 mg·l−1. Six to 8 h after administration the clearance was less than 50% of the initial value in the healthy volunteers and the corresponding fall in the renal patients was 33%. The concentration-dependent renal clearance of inulin was confirmed in “step-up” and “step-down” constant infusion studies in which clearances were measured at mean plasma concentrations ranging from 35.2 to 186.7 mg·l−1. These studies virtually excluded time, changes in posture and urine flow rate as important factors. There was no statistically significant fall in clearance during the first 2 h and kinetic analysis was based on data obtained over this time. Under these conditions the mean plasma half life, volume of distribution (Vss) and total body clearance of inulin in the healthy males, healthy females and patients with chronic renal failure were 73.2, 65.5 and 172.4 min, 10.5, 9.6 and 8.81·70 kg−1 and 113.3, 111.5 and 43.3 ml·min−1·70 kg−1 respectively. There were no sex differences in any of the kinetic variables. The mechanism of the concentration-dependent clearance of inulin is unknown but the findings are consistent with saturable renal tubular reabsorption. Care is required with the use of inulin for measurement of the glomerular filtration rate by the single injection technique.
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  • 50
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    European journal of clinical pharmacology 40 (1991), S. 631-633 
    ISSN: 1432-1041
    Keywords: Mefloquine ; ampicillin ; Thai subjects ; pharmacokinetics ; enterohepatic recycling ; drug interaction ; adverse effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single oral dose of mefloquine given either alone or with ampicillin has been studied in 8 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with ampicillin (1648 vs 1228 ng·ml−1), as well as a significantly reduced terminal half life (15.3 vs 17.7 days), mean residence time (20.1 vs 23.4 days) and volume of distribution at steady state (14.1 vs 19.4 l·kg−1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 5 days was significantly increased by ampicillin (4.86 vs 3.27 μg·ml−1 day). These changes in mefloquine disposition after antibiotic treatment may be due both to an increase in fractional bioavailability and a reduction in the enterohepatic recycling of mefloquine.
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  • 51
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    European journal of clinical pharmacology 40 (1991), S. 637-638 
    ISSN: 1432-1041
    Keywords: Roxatidine acetate ; sucraflate ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
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  • 52
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    European journal of clinical pharmacology 45 (1993), S. 357-361 
    ISSN: 1432-1041
    Keywords: Circadian rhythms ; Indomethacin ; Ketoprofen ; pharmacokinetics ; time-varying models ; nonsteroidal anti-inflammatory drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A one-compartment model with first-order absorption has provided good fits to five sets of indomethacin data and four sets of ketoprofen data taken at different times of day. There was substantial variation in the model parameters with time of administration and most of the features of this variation applied equally to both drugs. From the data examined, the source of variation appears to be mainly in the absorption phase and this was confirmed using a chronokinetic analysis, in which simultaneous fits were obtained with time-variant rate parameters. However, there may also be circadian variation in protein binding. The danger of quoting parameter values for either of these two drugs based on administration at a single time of day has been illustrated, and this may well be true for other drugs.
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  • 53
    ISSN: 1432-1041
    Keywords: Gamma-hydroxybutyric acid ; pharmacokinetics ; dose-proportionality
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg−1. The AUC increased disproportionately with the dose and so the apparent oral clearance decreased significantly as the dose was increased, whereas the terminal half-life and mean residence time increased. The peak plasma concentrations normalised to the lowest dose fell significantly with increasing doses, whilst the corresponding peak times increased. These findings suggest that both the oral absorption and the elimination of GHB are capacity-limited processes. GHB did not bind to significant extent to plasma proteins over the therapeutic concentration range. The pharmacokinetic parameters in healthy volunteers were not significantly different from those previously observed in alcohol-dependent patients with compensated alcoholic liver disease.
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  • 54
    ISSN: 1432-1041
    Keywords: Glyceryl trinitrate spray ; pharmacokinetics ; a/b-ratio ; pulmonary artery diastolic pressure ; finger pulse curve ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course and the magnitude of the effect of glyceryl trinitrate (GTN) on central venous (pulmonary artery diastolic pressure-PAPd) and peripheral arterial (a/b-ratio of the finger pulse wave) haemodynamics were compared in a randomized double-blind cross-over study in 12 patients suffering from congestive heart failure (NYHA II–III) with elevated PADd at rest (≥15 mm Hg). The data were obtained in a bioavailability study of two sprays of glyceryl trinitrate, which differed in their galenical characteristics and in the dose of GTN (0.4 mg vs. 0.8 mg). Following sublingual administration of each spray, PAPd, a/b-ratio and the plasma concentrations of GTN and its metabolites were measured up to 30 min. The relative bioavailability of GTN of the test preparation was estimated to be 157%, 161% and 147%, when calculated from the plasma concentration-time data or the integrated effect of GTN on a/b-ratio or PAPd, respectively. The mean time courses of the decrease in PAPd and the increase in the a/b-ratio of the finger pulse curve were mirror images. Thus, there was a strong correlation between the mean values of PAPd and a/b-ratio following the administration of glyceryl trinitrate. Since the slope of the relationship differed considerably between the patients, the magnitude of effect of GTN on PAPd in the individual patient could not be predicted from the changes in a/b-ratio.
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  • 55
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    European journal of clinical pharmacology 44 (1993), S. 463-466 
    ISSN: 1432-1041
    Keywords: Benazepril ; Proteinuria ; benazeprilat ; ACE inhibitor ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have investigated whether the pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril hydrochloride are altered with proteinuria by studying 8 patients with major proteinuria of different causes who were given a single dose of 10 mg p.o. The maximum plasma concentration of benazepril was found between 0.5 and 2 h after dosing (median 1 h). Its elimination was almost complete within 6 h. Peak plasma levels of benazeprilat, the active metabolite of benazepril, were observed between 1 and 6 h (median 2.5 h). The elimination of benazeprilat from plasma was biphasic, with mean initial and terminal half-lives of 3.0 and 17.3 h, respectively. On average, the pharmacokinetic parameters of benazepril and benazeprilat in the patients did not differ from those in a historical control group of healthy volunteers, but intersubject variability in the AUC and half-lives of benazeprilat was greater in the patients. Plasma ACE was completely inhibited from 1.5 to 6 h after dosing, and at 48 h the mean inhibition was still 42 %. Plasma renin showed substantial intersubject variation. Mean supine blood pressure (systolic/diastolic) was reduced from baseline by a maximum of 18/13 mm Hg at 6 h. Proteinuria was diminished after benazepril in 7 patients. In conclusion, the results of this study suggest that proteinuria in the nephrotic range does not require a change in benazepril dosage.
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  • 56
    ISSN: 1432-1041
    Keywords: dDAVP ; bioavailability ; gastrointestinal tract ; healthy volunteers ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP) from different regions of the gastrointestinal (GI) tract (stomach, duodenum, jejunum, ileum, colon, rectum) has been studied in 6 healthy, male volunteers aged 24 to 35 years, followed for 12 h after each drug administration. For i. v. administration the subjects received 4 μg dDAVP. For intestinal administration 400 μg dDAVP was directly applied to six distinct sites in the GI tract via two or four channel tubes with or without a distal occlusive balloon. Biological effects were assessed and plasma and urinary levels of dDAVP were measured using a specific, sensitive RIA. Urine osmolality remained elevated and diuresis decreased for 12 h following dDAVP administration irrespective of the site of application. After i. v. administration, the half-life of elimination of dDAVP was 60.0 min, plasma clearance 1.7 ml·min−1·kg−1, amount excreted in urine 2.0 μg and renal clearance was 0.8 ml·min−1·kg−1. The mean bioavailability (f) after gastric application was 0.19% (range 0.02–0.35%). f was 0.24% after duodenal application (range 0.04–0.62%), 0.19% after jejunal (range 0.01–0.41%), 0.03% after distal ileal (range 0.01–0.08%), 0.04% after proximal colonic (range 0.01–0.12%) and 0.04% after rectal (0.01–0.10%) application. The bioavailability was significantly higher in the three upper GI regions in comparison to the three lower regions. The bioavailability of dDAVP after gastric, duodenal and jejunal application was similar to that after swallowing a tablet in a previous study. Absorption from the ileum was lower than expected and no preferential site of absorption was found.
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  • 57
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    European journal of clinical pharmacology 42 (1992), S. 171-174 
    ISSN: 1432-1041
    Keywords: Quinine ; Malaria ; pharmacokinetics ; red blood cells ; plasma ; saliva ; adverse effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quinine has been studied in ten healthy adult Africans after intravenous infusion and oral ingestion of a 500 mg dose. Blood and saliva samples were collected over 48 h and quinine in plasma, red cells and saliva was determined by HPLC. Quinine was rapidly and almost completely absorbed after an oral dose, with absorption half-life of 0.53 h, a tmax of 1–3 h and a bioavailability of 88%. Analysis of the i. v. data gave an apparent volume of distribution of 3.6 1·kg−1 and a plasma clearance of 0.19 l·kg−1·h−1. The concentration-time curves for plasma, red cells and saliva had declining phases were approximately parallel, giving a similar half-life that in all three media. The half-lives after the i. v. infusion also did not different from those after oral administration. The dose was well tolerated by both methods of administration.
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  • 58
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    European journal of clinical pharmacology 42 (1992), S. 175-179 
    ISSN: 1432-1041
    Keywords: 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) ; Triflusal ; triflusal metabolite (HTB) ; pharmacokinetics ; protein binding ; ultrafiltration ; binding constant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) is the main active metabolite of the platelet anti-aggregant drug triflusal. Its binding to plasma proteins of rats and healthy volunteers in vitro and in vivo has been studied. Rats were given a single oral dose of 50 mg·kg−1 triflusal and the healthy volunteers received 300 mg as a single oral dose or a multiple dose regimen of 600 mg every 24 h and 300 mg every 8 h, both for 13 days. Protein-free HTB was obtained by ultrafiltration. Unbound and total HTB concentrations were determined by HPLC. HTB was primarily bound to albumin in plasma. The Scatchard plots suggested two types of binding sites for HTB on the albumin molecule. In rats, the binding constants (K=intrinsic affinity constant, n=number of binding sites) were K1=1.4×105 l·mol−1, n1=1.23, and K2=4.1×103 l·mol−1 and n2=3.77. The mean plasma concentration in rats after oral administration was 185 (37) μg·ml−1 (protein-free HTB: 2.44 (0.77)%). The binding constants in human plasma were K1=4.7×105 l·mol−1, n1=1.93, K2=4.3 l·mol−1 and n2=4.28. The plasma HTB concentration in man (n=8) was 35 μg·ml−1 (Cmax) after a single oral dose of triflusal 300 mg, 172.96 μg·ml−1 (Cmax·ss) during the multiple dosage regimen of 300 mg every 8 h, and 131 μg·ml−1 (Cmax·ss) during the multiple oral dose regimen of 600 mg every 24 h. Unbound HTB ranged from 0.27 to 0.43%, depending on dose. HTB had high affinity for plasma albumin, which was not saturable after therapeutic doses. It showed linear elimination.
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  • 59
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    European journal of clinical pharmacology 42 (1992), S. 181-185 
    ISSN: 1432-1041
    Keywords: Glycerol ; brain oedema ; serum ; cerebrospinal fluid ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Glycerol 50 g infused i. v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom was given 500 ml of a 10% solution IV over 4 h, serum and CSF were repeatedly sampled during and after the infusion and glycerol was measured enzymatically. The highest serum glycerol level of 191–923 mg/l was observed at the end of the infusion. The maximum CSF glycerol of 18.7–110.8 mg/l was attained 0–1 h after the end of the infusion. Elimination both from serum and CSF approximated a single-exponential decay; the elimination half-life from serum was 0.29–0.56 h compared to 1.03–3.68 h from CSF. In six of the seven cases there was a temporary reversal of the serum/CSF concentration gradient during glycerol elimination. The ratios of the AUCs of CSF and serum, which describe the overall penetration of glycerol into CSF, ranged from 0.09–0.31. In conclusion, the serum level of glycerol produced by giving 50 g IV glycerol over 4 h may not be sufficiently high reliably dehydrate to brain tissue in many patients, and the slow elimination of glycerol from the CSF may be related to the so-called rebound phenomenon.
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  • 60
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    European journal of clinical pharmacology 42 (1992), S. 187-191 
    ISSN: 1432-1041
    Keywords: Dipyrone ; Acetylation phenotype ; metabolism ; pharmacokinetics ; urinary excretion ; metabolite clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The formation and urinary excretion of the dipyrone metabolites, methylaminoantipyrine (MAA), aminoantipyrine (AA), formylaminoantipyrine (FAA) and acetylaminoantipyrine (AAA) were determined following administration of a single oral 1.0 g dose of dipyrone to 12 healthy volunteers. The AAA/AA plasma ratio showed that 3 subjects were slow and 9 were rapid acetylators. Pharmacokinetic parameters were determined separately for each group. A good correlation was found between the plasma and urine AAA/AA ratios. The renal clearance of the four metabolites was similar for both phenotypes. A significant difference in the rate of formation of dipyrone metabolites was found for AA, 0.25 (slow) vs 0.1 ml·min−1·kg−1 (rapid), and for AAA 0.75 (slow) vs 7.53 ml·min−1·kg−1 (rapid). There were comparable differences between slow and rapid acetylators in the AUC and the urinary excretion extrapolated to infinity for AA and AAA. The present results show that the kinetics of dipyrone metabolites in plasma and urine can provide a useful measure of the activity of the enzymes involved in their production.
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  • 61
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    European journal of clinical pharmacology 42 (1992), S. 197-201 
    ISSN: 1432-1041
    Keywords: Digoxin ; Salbutamol ; serum ; skeletal muscle digoxin ; pharmacokinetics ; drug interaction ; serum potassium
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of the β2-adrenoceptor agonist salbutamol has previously been shown to decrease serum digoxin concentration in healthy volunteers. A possible explanation of the phenomenon is a β2-adrenoceptor-mediated increase in the specific binding of digoxin to skeletal muscle. The present study was undertaken to further elucidate the effect of salbutamol on the pharmacokinetics of digoxin in man. Nine volunteers were studied on two occasions during salbutamol or placebo treatment. On test days salbutamol, 4 μg·kg−1·h−1 or saline was infused for 10 h, preceded and followed by four and three days, respectively, of oral administration. A single i. v. injection of digoxin 15 μg·kg−1, was given 20 min after starting the infusion. At the end of the infusion a muscle biopsy was taken from the vastus lateralis. Blood samples for the analysis of serum digoxin and potassium were repeatedly taken over 72 h. Urine was collected over a period of 24 h for determination of the renal excretion of digoxin and potassium. The serum digoxin concentration, expressed as the AUC 0–6 h was 15% lower during salbutamol infusion than during saline infusion. Salbutamol caused significantly faster elimination of digoxin from the central volume of distribution to deeper compartments. Salbutamol had no effect on the renal clearance of digoxin. The skeletal muscle digoxin concentration tended to be higher (48%) during salbutamol compared to placebo treatment. The serum potassium concentration was significantly lower after salbutamol compared to placebo, as was the rate of renal excretion of potassium. The results support the hypothesis that the salbutamol-induced decrease in serum digoxin is caused by increased distribution of digoxin to skeletal muscle (and possibly other tissues), and that this may be secondary to a β2-adrenoceptor-mediated increase in Na-K-ATPase activity.
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  • 62
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    European journal of clinical pharmacology 42 (1992), S. 203-207 
    ISSN: 1432-1041
    Keywords: Nicorandil ; pharmacokinetics ; angina pectoris ; uraemia ; adverse effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of oral nicorandil 20 mg 12 hourly for 9 doses was evaluated in 21 hospitalized patients with angina pectoris due to coronary heart disease and with normal and impaired renal function. Patients were divided into 3 groups based on creatinine clearance (CLCr): GROUP I (n=6) 〉 80 ml/min, GROUP II (n=8) 20–80 ml/min, and GROUP III (n=7) 〈 20 ml/min. After the first dose, the total clearance of nicorandil (CL) value did not change with increasing renal failure and so was not dependent on creatinine clearance. After the last dose CL was 51 l·h−1 in Group I, 44 l·h−1 in Group II and 56 l·h−1 in Group III, and it was not related to creatinine clearance. The percentage of the dose excreted in the urine was 0.4%. No significant difference was noted in any of the other pharmacokinetic parameters examined in the three groups, not even on comparing values obtained on the first and last days of treatment. The findings suggest that there is no need to change the dose of nicorandil in subjects with different degrees of renal failure.
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  • 63
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    European journal of clinical pharmacology 46 (1994), S. 83-85 
    ISSN: 1432-1041
    Keywords: Enuresis ; Oxybutynine chloride ; children ; pharmacokinetics ; adverse effects ; anticholinergic actions
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Anticholinergic adverse-effects in children treated with conventional doses of oxybutynine led us to measure plasma oxybutynine levels in children. 18 children, aged 5 to 13 y, who required treatment with oxybutynine chloride for daytime incontinence were studied. Plasma concentrations were measured on the fifth day of a course of treatment in which the dose was adapted to the child's body weight; the dose was given twice daily at 12-hour intervals. In 10 children aged between 5 and 8 y, the mean dose was 0.1 mg · kg−1. In 8 children aged between 10 and 13 years, the mean dose was 0.15 mg · kg−1. The highest concentration was usually found between 1 and 2 h after administration. The subsequent fall in concentration was rapid and after 6 h oxybutynine was no longer measurable in 14 of the children. The concentrations found were not different from those seen in adults given equivalent doses. The results show that plasma concentrations in children were not very different from those observed in adults if the dose were adapted to the body weight of the children. No special differences in paediatric use were revealed that might explain the particular adverse-effects. The results of the study argue against the dosage regimen proposed before these adverse events were detected. They strongly favour a dose adapted to the body weight of the child, with a 12-hour interval between doses.
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  • 64
    ISSN: 1432-1041
    Keywords: Steroid 5α-reductase inhibitor ; Testosterone metabolism ; MK-0434 ; pharmacodynamics ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A four-period, two-panel, single-rising-dose study (0.1–100 mg) was conducted in healthy males to investigate the pharmacodynamics, tolerability and pharmacokinetics of MK-0434, a steroid 5α-reductase inhibitor. MK-0434 was associated with a significant reduction in dihydrotestosterone, which was maximal at 24 h and maintained through 48 h post treatment. The maximum reduction was approximately 50 % and occurred at all doses above 5 mg (10, 25, 50 and 100 mg). MK-0434 appeared to have no effect on serum testosterone at these single doses. Rising single doses of MK-0434 were associated with an increase in Cmax and AUC but the changes were less than proportional to dose, most likely due to nonlinear absorption. MK-0434 given in single doses up to 100 mg was without significant adverse effects in healthy male volunteers. In summary, MK-0434 is a well-tolerated, potent, orally active 5α-reductase inhibitor in man.
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  • 65
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    European journal of clinical pharmacology 46 (1994), S. 261-265 
    ISSN: 1432-1041
    Keywords: Cystic fibrosis ; Cyclosporin ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Cyclosporin (CsA) is currently the main immunosuppressive agent used in organ transplantation with considerable improvement in graft survival. Oral CsA solution is highly lipophilic, and its bioavailability may be reduced in cystic fibrosis (CF) heart-lung transplant recipients with pancreatic, gastrointestinal, and hepatic insufficiency. The bioavailability of oral CsA solution in 7 CF transplant recipients (5 male and 2 female with a mean age of 27 years and a mean weight of 49 kg) and 3 non-CF heart-lung recipients (1 male and 2 female with a mean age of 41 years and a mean weight of 60 kg) was studied. Following intravenous CsA administration, the kinetic curves were similar with no significant difference in the volume of distribution and clearance of CsA demonstrated between the CF and non-CF groups. The mean daily dose of oral CsA in 7 CF subjects (23.3 mg·kg−1) was significantly higher than the 3 non-CF heart-lung recipients (4.8 mg·kg−1). The mean maximum blood concentration of CsA for the oral dose was 776 ng·ml−1 for the 7 CF subjects, which was comparable with the mean peak values of 789 ng·ml−1 for the 3 non-CF control subjects. Poor enteral absorption of CsA probably accounts for the significantly lower mean bioavailability in the 7 CF subjects (14.9%) compared with the 3 non-CF control subjects (39.4%). The effects on the bioavailability of oral CsA solution by pancreatic enzymes (Creon) and histamine-2 antagonist (ranitidine) were also evaluated in the 7 CF subjects. No significant difference was demonstrated.
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  • 66
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    European journal of clinical pharmacology 44 (1993), S. 247-251 
    ISSN: 1432-1041
    Keywords: Proguanil ; Pregnancy ; Malaria ; cycloguanil ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and whole blood concentrations of proguanil, its active metabolite cycloguanil, and the inactive metabolite 4-chlorophenyl-biguanide, were measured by HPLC in 10 healthy Karen women in the last trimester of pregnancy, following a 200 mg single oral dose of proguanil. Four of these women were restudied 2 months after delivery. The pharmacokinetic properties of proguanil were similar during and after pregnancy. Median peak plasma concentrations of proguanil during pregnancy and following delivery were 212 and 215 ng·ml−1, and occurred at 4.5 and 5 h, respectively. Mean plasma AUC values for proguanil during and following pregnancy were 94 and 98 ng·h·ml−1·kg−1, respectively. Corresponding whole blood AUC values were 361 and 396 ng·h·ml−1·kg−1. The mean elimination half lives and mean residence times of proguanil in plasma and whole blood were 12.3 and 19.6 h and 13.8 and 20.7 h respectively during pregnancy. Following pregnancy these values were 17.1 and 19.7 h for plasma and 19.7 h and 20.2 h for whole blood respectively. Mean peak plasma and whole blood concentrations of cycloguanil following pregnancy were 25 and 22 ng·ml−1 respectively. During pregnancy peak cycloguanil concentrations in both plasma and whole blood were markedly lower, 13 and 12 ng ml−1, respectively. Two pregnant women (neither of whom were restudied) were probably poor metabolisers of proguanil. The mean ratio of proguanil to cycloguanil plasma AUC was 16.7 in the third trimester of pregnancy and 7.8 following pregnancy, compared with less than 5 in previously reported studies. The concentrations of 4-chlorophenylbiguanide in both plasma and whole blood in pregnant subjects were also lower than those after pregnancy. These data show that blood concentrations of the active antimalarial metabolite cycloguanil are reduced in late pregnancy and that the currently recommended dose of proguanil could be inadequate for antimalarial prophylaxis in pregnant women.
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  • 67
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    European journal of clinical pharmacology 44 (1993), S. 265-269 
    ISSN: 1432-1041
    Keywords: Cyclosporine ; Renal transplantation ; pharmacokinetics ; intraindividual variation ; circadian variation
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The intraindividual variability and circadian variation of oral cyclosporine (CsA) pharmacokinetics were studied over 24 h in 18 renal transplant recipients at steady state, and in 10 of the patients during a second 24 h period. The absolute percentage intraindividual difference in daytime AUC (0–12 h) ranged from 2% to 54% (mean 30%), and the corresponding variability in nighttime AUC (0–12 h) ranged from 5% to 80% (mean 34%). The pharmacokinetic variables t1/2, tmax and Cmax were more variable than the AUC (0–12 h) both during the day and at night. The evening trough level was significantly lower than the morning trough level; 185 ng · ml−1 versus 223 ng · ml−1. This, together with a significantly longer t1/2 in the night than the day, suggested circadian variability in the pharmacokinetics of CsA. In a separate retrospective study in 162 renal transplant recipients given CsA by constant intravenous infusion, repeated CsA blood concentration measurements at steady state showed lower concentrations during the day than the night, suggesting higher CsA clearance during daytime. It is concluded that CsA pharmacokinetics in renal transplant recipients, besides the well-known interindividual variability, also displays large intraindividual variability as well as circadian variation. Our findings further emphasize the necessity and difficulty of pharmacological monitoring in the clinical use of CsA in organ transplantation.
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  • 68
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    European journal of clinical pharmacology 44 (1993), S. 301-302 
    ISSN: 1432-1041
    Keywords: Adriamycin ; Haemodialysis ; adriamycinol ; pharmacokinetics ; moment analysis
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  • 69
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    European journal of clinical pharmacology 44 (1993), S. 305-306 
    ISSN: 1432-1041
    Keywords: Atenolol ; bioavailability ; intestinal absorption ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We investigated the dose proportionality after the intake of oral atenolol 25, 50, 100 and 150 mg. Standard tablets were taken by 8 healthy volunteers in randomised order of doses. The area under the curve divided by dose did not differ between the doses, indicating that the absorption of this hydrophilic compound, with known incomplete bioavailability, was constant over the range tested.
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  • 70
    ISSN: 1432-1041
    Keywords: Esmolol ; β1-Adrenoceptor antagonist ; tricresylphosphate ; pharmacokinetics ; effect kinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of esmolol at different rates of infusion (100, 250 and 500 μg·kg−1 BW·min−1) were compared with β-adrenoceptor occupancy (β1 and β2, estimated by a subtype selective radioreceptor assay) and plasma concentrations of esmolol and its acid metabolite were measured by HPLC. Up to a rate of infusion of esmolol of 500 μg·kg−1 BW·min−1 there was a maximal β1-receptor occupancy of 84.7% while β2-receptor occupancy was below the detection limit; confirming the β1 selectivity of esmolol. Exercise-induced increases in heart rate and systolic blood pressure were reduced by esmolol in a dose-dependent manner. The estimated EC50 values of rate of infusion for the reduction in heart rate and systolic blood pressure during exercise were 113 and 134 μg·kg−1 BW · min−1, respectively. Additionally, heart rate and systolic blood pressure were reduced moderately at rest. Because of the short elimination half-life of esmolol caused by the rapid hydrolysis to its acid metabolite, 45 min after end of infusion high plasma concentrations of the metabolite (maximally 80 μg·ml−1) but no esmolol were detectable. Since no in vivo effects have been observed, despite the presence of high plasma concentrations of the metabolite, the metabolite did not participate in the observed effects up to an infusion rate of esmolol of 500 μg·kg−1 BW·min−1. The plasma concentrations of antagonist detected by radioreceptor assay and plasma concentrations of esmolol detected by HPLC showed a good correlation (r=0.97). Since the cardiovascular effects, determined before and 45 min after termination of infusion of esmolol were similar, it can be concluded that the observed effects on heart rate and systolic blood pressure are exclusively mediated by esmolol.
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  • 71
    ISSN: 1432-1041
    Keywords: Ramipril ; Piretanide ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers. The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0–4 h) and ramiprilat (0–24 h) (from 15.8 to 19.8 ng·ml−1·h, and from 63.4 to 74.6 ng·ml−1·h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73 % of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide. The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril. Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers.
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  • 72
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    European journal of clinical pharmacology 46 (1994), S. 573-574 
    ISSN: 1432-1041
    Keywords: Standard deviation ; Arithmetic mean ; pharmacokinetics
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  • 73
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    European journal of clinical pharmacology 46 (1994), S. 565-567 
    ISSN: 1432-1041
    Keywords: Phenytoin ; Saliva ; therapeutic drug monitoring ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of atropine-induced reductions in saliva flow rate on saliva phenytoin concentrations were evaluated in a randomised placebo-controlled crossover study in a group of epileptic patients stabilised on the drug. Pretreatment with atropine caused significant reductions in saliva flow rates during the first 4 h, compared to saline. The AUC0–4 h for saliva flow rate was significantly reduced by atropine (245 g vs 327 g) and the saliva phenytoin AUC0–4 h was significantly increased (5.6 μg · ml−1 · h vs 4.5 μg · ml−1 · h) without affecting plasma phenytoin concentrations. The saliva/plasma phenytoin AUC0–4 h ratio was therefore significantly increased by atropine (0.15 vs 0.12). However, there was a poor correlation between saliva/plasma phenytoin concentration ratios and saliva flow rates for the two treatments in the individual patients (correlation coefficient ranged from 0.25 to 0.65). These findings demonstrate that saliva phenytoin concentrations are increased by reductions in saliva flow rate. Caution is therefore required when saliva phenytoin concentrations are used for therapeutic monitoring in the presence of factors which may affect saliva flow rate.
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  • 74
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    European journal of clinical pharmacology 47 (1994), S. 61-65 
    ISSN: 1432-1041
    Keywords: Cyclosporine A ; kidney transplant ; nephrotic syndrome ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetic parameters of cyclosporine (CsA) were determined in 23 kidney transplant recipients and 19 children with nephrotic syndrome, after intravenous and oral administration. The mean bioavailability was 39 %, blood clearance was 0.55 l · h-1 · kg-1 and volume of distribution at steady-stade was 2.77 l · kg-1. The absorption profile was monophasic (67 %), biphasic (29 %) or poor (4 %). The maximum blood concentration of CsA was significantly higher in children with a monophasic profile than in children with a biphasic profile (550 vs 380 ng · ml-1). Blood clearance was significantly higher in the transplant recipients than in the patients with nephrotic syndrome (0.65 vs 0.43 l · h-1 · kg-1. Although age, haematocrit, creatinine clearance, serum albumin and cholesterol differed between the two groups, only haematocrit and creatinine clearance were significantly (negatively) correlated with CsA clearance.
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  • 75
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    European journal of clinical pharmacology 47 (1994), S. 81-84 
    ISSN: 1432-1041
    Keywords: Dihydrotachysterol ; bioavailability ; pharmacokinetics ; human ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability of four preparations containing dihydrotachysterol (DHT2) was tested in two separate trials with administration of single, oral doses of 1 mg per individual. The relative bioavailability of corresponding preparations (capsules vs capsules and oral solution vs oral solution) was tested in a randomised, crossover pattern within the same group of volunteers. Two different groups of 24 healthy volunteers took part in each trial. Solution and capsule bioavailability was also compared inter-individually. A new sensitive HPLC-method (quantification limit 0.5 ng · ml-1) was used for the measurement of DHT2 concentration in serum. Three of the preparations tested had a similar bioavailability (mean AUC values of 195.5–223 ng · h · ml-1); the bioavailability of the fourth preparation (A.T.10 oral solution) was considerably lower (mean AUC value 111.5 ng · h · ml-1). The present dosage recommendations of all four preparations are identical. A new dosage recommendation is thus required for the oral solution with low bioavailability (A.T.10).
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  • 76
    ISSN: 1432-1041
    Keywords: Doxycycline ; bioavailability ; pH dependent absorption ; pharmacokinetics ; carrageenate ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of increased gastric pH (obtained by pre-treatment with omeprazole) on the bioavailability of doxycycline monohydrate and doxycycline carrageenate has been investigated in 24 healthy volunteers, using an open, randomised, four-treatment, four-period, crossover, 2×2 factorial design. Each subject received a single dose of 100 mg of each of the doxycycline formulations with and without pre-treatment with omeprazole (40 mg daily for 7 days). The two formulations were bioequivalent (rate and extent) during fasting without omeprazole pre-treatment, whereas after omeprazole, the monohydrate showed a highly significant decrease in bioavailability (38% for AUC and 45% for Cmax) compared to the carrageenate formulation, which was not affected by prior administration of omeprazole. Many of the subjects did not reach a therapeutic plasma level of doxycycline during the combination of omeprazole and doxycycline monohydrate, and most adverse events (mainly gastrointestinal) were reported after this combination. As large populations of patients have a high gastric pH due to frequent use of H2-blockers, proton pump inhibitors and antacids, as well as to physiological achlorhydria, the decreased absorption of doxycycline monohydrate may well have a clinical impact, for example when the patients are treated with tetracyclines for an infection.
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  • 77
    ISSN: 1432-1041
    Keywords: Medifoxamine ; pharmacokinetics ; pharmacodynamics ; elderly volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and psychomotor effects of medifoxamine, a 5 HT reuptake inhibitory antidepressant, were studied in healthy elderly volunteers after single and multiple dosing. The elimination half life (t1/2z) after single doses of 300 mg was 2.8 h — almost identical to that found in young volunteers. After seven days of dosing at 100 mg three times daily the mean corrected AUC after 300 mg significantly increased from 1.04 to 1.34 mg.h.l−1 and t1/2z increased to 4.0 h (NS). There were no significant changes in critical flicker fusion frequency, symbol digit substitution, continuous attention or choice reaction times.
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  • 78
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    European journal of clinical pharmacology 46 (1994), S. 179-180 
    ISSN: 1432-1041
    Keywords: Teicoplanin ; haemodialysis ; renal failure ; pharmacokinetics
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  • 79
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    European journal of clinical pharmacology 46 (1994), S. 237-242 
    ISSN: 1432-1041
    Keywords: Metoprolol ; bioavailability ; bioequivalence ; receptor binding assay ; pharmacokinetics ; sustained release formulation
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability and pharmacodynamic bioequivalence of a conventional and an experimental sustained-release formulation of 100 mg metoprolol tartrate were studied in a randomised cross-over study in seven healthy volunteers by assessing over 24 h the plasma kinetics of R,S-metoprolol, its β1-adrenoceptor binding component, and by determining the extent to which the active drug moiety in plasma occupied rabbit lung β1-and rat reticulocyte β2-adrenoceptors. The formulations differed markedly in their kinetic characteristics: the peak plasma concentration (Cmax) of R,S-metoprolol after administration of the conventional formulation was 140 ng·ml−1, (n=7) and it was approximately one-third of that after the sustained-release formulation, 49 ng·ml−1, (n=6); the AUC0–24 h-values for the formulations were 700 and 310 ng·h·ml−1, respectively. The Cmax for the β1-adrenoceptor binding component of metoprolol was 180 ng·ml−1 (n=7) after administration of the conventional, and 74 ng·ml−1 after administration of the sustained-release formulation. The corresponding AUC0–24 h-values for the receptor binding component were 920 and 470 ng·h·ml−1 (n=7). Thus, the kinetic differences between R,S-metoprolol and the β1-receptor binding component were considerable and they were affected by the type of formulation. In general, after administration of the sustained-release formulation, the percentage β1- and β2-adrenoceptor occupancy of metoprolol in plasma was 5–15% less than after administration of the conventional formulation. At 0.5–1.5 h after drug intake the average β1-adrenoceptor occupancy of the conventional formulation varied between 80–90% and that of the sustained release formulation between 20–76%. At these times the differences in receptor occupancy were significant; at 0.5–2 h after drug intake the average β2-adrenoceptor occupancy of the conventional formulation varied from 20–30%, and that of the sustained-release formulation was 2–17%. At other times the difference in receptor occupancy between the formulations was not significant. The results demonstrate that plasma concentration-kinetics were more discriminating than β-adrenoceptor-binding in analysing bioequivalence. It was possible to determine the bioavailability of the active ingredient of metoprolol and to study pharmacodynamic bioequivalence by using receptor binding assays.
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  • 80
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    European journal of clinical pharmacology 46 (1994), S. 575-575 
    ISSN: 1432-1041
    Keywords: Renal clearance ; pharmacokinetics
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  • 81
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    European journal of clinical pharmacology 47 (1994), S. 75-79 
    ISSN: 1432-1041
    Keywords: Diltiazem ; Angina pectoris ; controlled release formulation ; metoprolol ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Diltiazem CR tablets 120 mg b.i.d. for 1 week were compared with plain tablets 60 mg q.i.d. in 13 healthy male volunteers in a study of pharmcokinetic variables. Their antianginal efficacy was also compared in 23 patients with stable angina pectoris who were already on metoprolol. Both studies were of randomised, cross over design, and the clinical study was double blind. The pharmacokinetic variables of the two formulations were very similar except for the longer tmax of 4.4 h for diltiazem CR in comparison to 2.9 h for the plain tablets. The mean relative bioavailability of diltiazem CR in comparison with plain tablets was 1.14. The clinical study showed that after four weeks on diltiazem CR 120 mg b.i.d. or diltiazem plain tablets 60 mg q.i.d. in addition to metoprolol, there were significant decreases in weekly anginal attacks from 11 to 5 attacks/week, the number of nitroglycerin tablets consumed from 6 to 3 tablets/week, and an increase in the maximum workload from 116 to 126 and 123 W for diltiazem CR and plain diltiazem tablets, respectively, as compared to placebo. Five of the patients were angina free during diltiazem treatment. No difference in antianginal efficacy between the two preparations was seen. It was concluded that CR 120 mg b.i.d. appears bioequivalent to plain diltiazem tablets 60 mg q.i.d.
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  • 82
    ISSN: 1432-1041
    Keywords: Oxcarbazepine ; 10,11-dihydro-10-hydroxy-carbamazepine ; renal impairment ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have studied the effect of renal impairment on the pharmacokinetics of oxcarbazepine, its active monohydroxy-metabolite (which predominates in plasma), their glucuronides, and the inactive dihydroxy-metabolite after a single oral dose of oxcarbazepine (300 mg). Six subjects with normal renal function and 20 patients with various degrees of renal impairment participated. The mean areas under the plasma concentration-time curves of oxcarbazepine and its monohydroxy-metabolite were 2–2.5-times higher in patients with severe renal impairment (CLCR〈10 ml·min−1) than in healthy subjects. The apparent elimination half-life of the monohydroxy-metabolite [19 (SD 3) h] in these patients was about twice that in healthy subjects. The effect of renal impairment on the plasma concentrations of glucuronides was more marked. The renal clearances of the unconjugated monohydroxy-metabolite and its glucuronides (the main compounds recovered in urine) correlated well with creatinine clearance. The maximum target dose in patients with slight renal impairment (CLCR〉30 ml·min−1) should not be changed. In patients with moderate renal impairment (CLCR10–30 ml·min−1) it should be reduced by 50%. In patients with severe renal impairment (CLCR〈10 ml·min−1), the glucuronides of oxcarbazepine and its monohydroxy-metabolite are likely to accumulate during repeated administration, and dosage adjustment of oxcarbazepine in these patients could not be proposed from this single administration study.
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  • 83
    ISSN: 1432-1041
    Keywords: Halofantrine ; Malaria falciparum ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Halofantrine is a new blood schizontocidal drug used for the treatment of multidrug-resistant falciparum malaria. The pharmacokinetics of halofantrine (HAL) and its principal metabolite, N-desbutylhalofantrine (BHAL), was investigated in 6 adult male patients of Melanesian origin with uncomplicated falciparum malaria. The patients received 500 mg of halofantrine hydrochloride at times 0, 6 and 12 h (total 1.5 g). All patients responded to treatment with a mean parasite clearance time of 52.7 h and a mean fever clearance time of 33.8 h. The following kinetic parameters (mean values) were determined for HAL and BHAL, respectively: maximum plasma concentration (Cmax)=896 and 491 ng·ml−1; time to reach the Cmax (tmax)=15 and 56 h; elimination half-life (t1/2)=91 and 79 h and the mean residence time (MRT)=71 and 102 h. Based on the clinical response the plasma concentrations of HAL and BHAL were adequate for the treatment of uncomplicated falciparum malaria in the 6 patients.
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  • 84
    ISSN: 1432-1041
    Keywords: Fosinopril ; fosinoprilat ; CAPD ; ACE-inhibitor ; pharmacokinetics ; pharmacodynamics ; peritoneal dialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated after the oral administration of 10 mg of fosinopril sodium to 6 chronic ambulatory peritoneal dialysis (CAPD) patients. The results from 1 patient are reported separately because of the presence of concomitant liver dysfunction. The mean t1/2, Cmax, tmax, and AUC values for 5 of the CAPD patients were 19.5 h, 202 ng·ml−1, 4.8 h, and 3.19 μg·h·ml−1, respectively. Values for 1 CAPD patient with liver dysfunction were t1/2 of 65.4 h, Cmax of 182 ng·ml−1, tmax of 9 h, and AUC of 18.1 μg·h·ml−1. Peritoneal clearance of fosinoprilat was negligible, ranging from 0.07 to 0.23 ml·min−1. Serum ACE activity remained significantly suppressed at 24 and 48 h after fosinopril sodium administration with mean decreases from baseline of 94.2% and 70.6%, respectively. ACE activity was suppressed to an even greater degree in the patient with liver dysfunction, remaining 97% inhibited 72 h after drug administration. Plasma renin activity (PRA) increased and plasma aldosterone concentrations decreased following drug administration. Mean arterial pressure did not change appreciably throughout the study. Dosage reductions may not be necessary in the majority of dialysis patients.
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  • 85
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    European journal of clinical pharmacology 41 (1991), S. 171-174 
    ISSN: 1432-1041
    Keywords: Bisoprolol ; pharmacokinetics ; obesity ; blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single i. v. dose of dlbisoprolol 0.16 mg·kg−1 ideal body weight has been studied in 8 obese women (mean weight 91 kg; 161% of ideal body weight) and 8 non-obese women (51 kg; 94% of ideal body weight). Compared to the controls, the obese subjects showed an increase in the total apparent volume of distribution (Vz) (182 vs 135 1) and a decrease in Vz per kg body weight (2 vs 2.7 l·kg−1). There was a negative correlation between Vz l·kg−1 and the percentage of ideal body weight (r=−0.672). Total body clearance was increased, but t1/2 and renal clearance was unchanged. It is concluded that tissue diffusion of bisoprolol in obese subjects is limited, despite its lipophilicity, possibly because of alteration in the blood flow to adipose tissue produced by bisoprolol.
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  • 86
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    European journal of clinical pharmacology 41 (1991), S. 175-178 
    ISSN: 1432-1041
    Keywords: Bopindolol ; pharmacokinetics ; beta-adrenoceptor blocker ; age ; hydrolysed bopindolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Steady-state pharmacokinetic parameters of the new, long-acting beta-adrenoceptor blocker bopindolol have been measured in 17 young and 20 elderly healthy men. The t1/2β and the AUC(0→24 h) of hydrolysed bopindolol (the active metabolite) were both increased (40% and 26%, respectively) in the elderly subjects but tmax, Cmax and CL/f were not altered. However, after adjusting the parameters to allow for the different average body weights of the two groups, Cmax and CL/f became significantly different (+29% and −30%, respectively). AUC(0→24 h) was increased by 41%. The changes of up to 41% in pharmacokinetic parameters were smaller than the alterations of 50–100% usually seen when titrating doses of antihypertensive drugs. The clinical relevance of the effects was not examined, but similar changes have been reported for other beta-blockers which did not appear to be clinically relevant and did not affect the dosage required to treat hypertension.
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  • 87
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    European journal of clinical pharmacology 41 (1991), S. 179-183 
    ISSN: 1432-1041
    Keywords: Cefadroxil ; saturable absorption ; saturable renal tubular reabsorption ; cephalexin ; competitive inhibition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic behaviour of cefadroxil was dose-dependent in healthy male volunteers following the oral administration of single doses of 5, 15, and 30 mg · kg−1. As the dose of cefadroxil increased from 5 to 15 and 30 mg · kg−1, the peak plasma concentrations, normalized to 5 mg · kg−1, decreased significantly from 15.1 to 10.7 and 7.6 mg·l−1, while the corresponding normalized areas under the plasma concentration-time curves from 0 to 2 h decreased significantly from 1258 to 946 and 801 min·mg·l−1. When the same subjects were given 5 mg·kg−1 of cefadroxil together with 45 mg·kg−1 of cephalexin, the absorption of cefadroxil was slowed to a similar or greater extent than with the high dose of cefadroxil. Although the absorption rate decreased as the dose increased, the systemic availability of cefadroxil was essentially complete at all doses, as judged by the 24 h urinary recoveries of the antibiotic. Kinetic analysis of the plasma concentration-time curves gave the best fit with a zero-order followed by a first-order absorption process, consistent with saturable intestinal absorption of cefadroxil. The elimination rate of cefadroxil was directly related to dose and plasma concentrations, and the clearance at the dose of 5 mg·kg−1 was significantly increased by the simultaneous administration of high-dose cephalexin. The renal clearance of cefadroxil ranged from 98 ml·min·l−1 at total plasma cephalosporin (cefadroxil + cephalexin) concentrations less than 2.5 mg·l−1 to 156 mg·l−1 at concentrations greater than 40 mg·l−1. These findings are consistent with saturable active gastrointestinal absorption and renal tubular reabsorption of cefadroxil, with competitive inhibition of both processes by cephalexin.
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  • 88
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    European journal of clinical pharmacology 41 (1991), S. 245-250 
    ISSN: 1432-1041
    Keywords: Org 10172 ; Digoxin ; heparinoid ; pharmacokinetics ; pharmacodynamics ; drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Potential pharmacokinetic and pharmacodynamic interactions between a new low molecular weight heparinoid Org 10172 (bolus injection of 3250 anti-Xa units) and digoxin (0.25 mg once daily for 8 days) were studied in 6 healthy male volunteers using an open, randomised three-way cross-over design. Digoxin produced a slight increase in clearance of anti-Xa activity from 4.3 to 4.8 ml·min−1, while plasma anti-thrombin and thrombin generation inhibiting (TGI) activity remained unchanged. Digoxin did not affect the actions of Org 10172 on the clotting tests. In the presence of Org 10172 there was a reduction in the AUC of digoxin during one dosing interval after the seventh digoxin tablet from 20 to 17 ng·ml−1·h, and a significant reduction in the average serum digoxin conentration. Since renal digoxin clearance was not significantly changed this probably might be due to a change in the non-renal clearance of digoxin. Atrio-ventricular node conduction, as measured by PR-time intervals, remained unchanged during all three treatments. In conclusion, although the pharmacokinetics of Org 10172 and digoxin were slightly changed by the combination, it is probably safe to administer Org 10172 and digoxin simultaneously. The clinical relevance of the slight decrease in plasma anti-Xa activity levels cannot yet be defined.
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  • 89
    ISSN: 1432-1041
    Keywords: Tiaprofenic acid ; children ; pharmacokinetics ; NSAID
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary. Twelve healthy children in three age groups anaesthetized for minor surgery were given a single oral dose of tiaprofenic acid (3 mg · kg−1) (TA). Seven blood samples and zero to 8 and 8 to 24 h urines were collected. TA concentrations in plasma and urine were measured by HPLC. No significant difference was found between the age groups in the kinetic parameters of TA and no correlation was found between these parameters and age; tmax=2.12h, Cmax=8.78mg · l−1, AUC(0→8 h) 33.9mg · h · l−1, AUC=39.3 mg · h · l−1, t1/2=2.35 h, Vz=0.319 l · kg−1, CL=0.094 l · h−1 · kg−1. Renal clearance was 14 ml · h−1. kg−1. 33% of the TA dose was recovered in the 24 h urine, 48% of which was conjugated, whereas in adults, TA is only found in urine as conjugates. The apparent plasma clearance was significantly higher (56%) than in 12 healthy adults given 1.5 mg · kg−1 TA. Volume of distribution and t1/2 did not significantly differ between children and adults. Since no relationship has been established between plasma TA and either efficacy or toxicity, a different dose regimen cannot be recommended in 3–11 year-old children from that in adults.
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  • 90
    ISSN: 1432-1041
    Keywords: Alprazolam ; benzodiazepines ; pharmacokinetics ; pharmacodynamics ; sublingual dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We gave 12 healthy male volunteers 1 mg of alprazolam or placebo on three occasions after a standard breakfast in a double-blind, randomized, single-dose, three-way crossover study. The three trials were: (a) oral alprazolam and sublingual placebo; (b) oral placebo and sublingual alprazolam; (c) placebo by both routes. Plasma alprazolam concentrations during 24 h after each dose were measured by electron-capture gas-liquid chromatography. Peak plasma concentrations were reached later after sublingual than oral dosage (2.8 vs 1.8 h, P〈0.01). Other kinetic variables were not significantly different: peak plasma concentration, 11.3 vs 12.0 ng·ml−1; elimination half-life, 12.5 vs 11.7 h; and total area under the plasma concentration versus time curve, 197 vs 186 h·ng·ml−1. Pharmacodynamic measures showed that sublingual and oral alprazolam both produced sedation, fatigue, impaired digit symbol substitution, slowing of reaction time, and impairment of the acquisition and recall of information. These changes were initially observed at 0.5 h after dosage and lasted up to 8 h. In general the two routes were significantly different from placebo but not from each other.
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  • 91
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    European journal of clinical pharmacology 42 (1992), S. 445-448 
    ISSN: 1432-1041
    Keywords: Ethanol ; whole blood ; plasma ; total body water ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ethanol in plasma and whole blood have been investigated and the results used to estimate the volume of total body water (TBW) by means of the dilution principle. Fifteen men (mean age 62 y) were given 0.6 g ethanol/kg body weight as an intravenous infusion over 1 h. The peak concentration of ethanol in plasma was 120 mg·dl−1 compared to 108 mg·dl−1 for whole blood. The disappearance rate of ethanol from plasma was 18.6 mg·dl−1·h−1 compared to 17.0 mg·dl−1·h−1 for the whole blood concentration-time data. The apparent volume of distribution of ethanol (Vz) was 0.54 l·kg−1 according to plasma kinetics compared to 0.59 l·kg−1 for the kinetics derived from whole blood. The mean area under the curve (AUC) was 294 mg·dl−1×h for plasma kinetics compared to 266 mg·dl−1×h for whole blood. The TBW was 40.9 l or 50.9% of body weight for the plasma concentration-time data. This agreed well with the 40.3 l or 50.1% of body weight obtained using whole blood.
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  • 92
    ISSN: 1432-1041
    Keywords: Methylprednisolone ; Rheumatoid arthritis ; bioavailability ; pharmacokinetics ; clinical response ; pulse steroid therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A commercially available 1.0 g intravenous (i.v.) dosage formulation of methylprednisolone, as the sodium hemisuccinate salt (Solu MedrolR, Upjohn) was administered both parenterally and orally (pulse steroid therapy) on separate occasions, to eight elderly (mean 65 y) patients with active rheumatoid arthritis. The relative oral bioavailability of the sterol was 69.2%. Elimination of methylprednisolone was prolonged when given orally; the mean residence times were 7.23 h and 3.94 h for oral and i.v. administrations, respectively. Clinical response to pulse steroid therapy was no different with respect to route of administration. There were no significant differences in standard clinical and laboratory assessments of disease activity when the two therapies were compared. Oral administration of methylprednisolone in patients requiring high-dose pulse steroid therapy is convenient and avoids the discomfort and inconvenience associated with i.v. administration.
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  • 93
    ISSN: 1432-1041
    Keywords: Acetyl-L-carnitine ; Senile Dementia of Alzheimer Type ; pharmacokinetics ; plasma concentration ; cerebrospinal fluid concentration ; carnitine metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetyl-L-carnitine (ALC), a physiological component of the L-carnitine family, has been proposed for treating Alzheimer's disease in pharmacological doses. As this condition requires prolonged therapy, its kinetics has been examined after a multiple dose regimen, involving different routes of administration, in 11 patients suffering from Senile Dementia of Alzheimer Type. The study design comprised a 3-day basal observation period, sham treatment with repeated blood sampling; treatment with 30 mg·kg−1 i.v. given twice for 10 days (plasma kinetics was studied on the 7th day), and 50 days of 2.0 g/day p.o. given in three daily doses. Total acid soluble L-carnitine, L-carnitine and acetyl-L-carnitine in plasma and CSF were evaluated using an enantioselective radioenzyme assay. Short chain L-carnitine esters were calculated as the difference between total and free-L-carnitine. The plasma concentrations of individual components of the L-carnitine family did not change during the three days of the basal period, nor were they affected during the sham therapy period. Following the i.v. bolus injections, the plasma concentrations showed a biphasic curve, with average t1/2 of 0.073 h and 1.73 h, respectively. At the end of oral treatment, plasma acetyl-L-carnitine and L-carnitine short chain esters were significantly higher than during the run-in phase. The CSF concentrations paralleled those in plasma, suggesting that ALC easily crosses the blood-brain barrier. It is concluded that i.v. and oral administration of multiple doses of ALC can increase its plasma and CSF concentration in patients suffering from Alzheimer's disease.
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  • 94
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    European journal of clinical pharmacology 42 (1992), S. 95-99 
    ISSN: 1432-1041
    Keywords: Ofloxacin ; Haemodialysis ; ofloxacin metabolites ; pharmacokinetics ; multiple doses ; dosage selection ; renal failure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 7 patients with end-stage renal disease on regular haemodialysis were treated orally with a loading dose of 200 mg ofloxacin and multiple maintenance doses of 100 mg per 24 h for 10 days. The pharmacokinetics of ofloxacin and its metabolites were studied at the end of the treatment period. Plasma and dialysate concentrations of ofloxacin and ofloxacin metabolites were measured by HPLC. Peak (3.1 mg·1−1) and trough levels (1.6 mg·1−1) and the AUC of ofloxacin were comparable to the values in healthy volunteers given 300 to 400 mg ofloxacin p.o. The mean half-life, determined in the dialysis-free interval (t1/2β) and during the haemodialysis session (t1/2HD), was 38.5 h and 9.9 h, respectively. Extrarenal clearance (32.7 ml·min−1) was unchanged as compared to that reported in healthy volunteers after a single dose of ofloxacin. The fractional removal by haemodialysis amounted to 21.5%. Two metabolites, ofloxacin-N-oxide and demethyl-ofloxacin, were detected in plasma. Despite prolonged t1/2β of both metabolites (66.1 and 50.9 h) and multiple doses of ofloxacin the peak concentrations of the metabolites reached only 14% and 5% of that of the parent drug, respectively. It is concluded that in patients on regular haemodialysis treatment the dosage adjustment employed resulted in safe and therapeutically favourable plasma concentrations. The observed accumulation of ofloxacin metabolites does not appear to have any toxic or therapeutic significance.
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  • 95
    ISSN: 1432-1041
    Keywords: Methotrexate ; non-steroidal anti-inflammatory drugs (NSAIDs) ; interaction ; disposition ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.
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  • 96
    ISSN: 1432-1041
    Keywords: Midazolam ; pharmacokinetics ; intranasal ; intravenous ; children ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve children 1–5 y old were randomly assigned to receive midazolam 0.2 mg·kg−1 either by the intravenous (IV) or intranasal (IN) routes. After IN administration the rapid onset of absorption was observed (tmax 12 min). After both routes of administration the half-life was similar (2.2 h IN and 2.4 h IV). After IN administration the apparent plasma clearance and volume of distribution were about twice as high as after IV administration. The results are consistent with an estimated mean bioavailability of 55%.
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  • 97
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    European journal of clinical pharmacology 41 (1991), S. 359-361 
    ISSN: 1432-1041
    Keywords: Diabetes ; Antipyrine ; undernutrition ; drug metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In developing countries diabetics frequently suffer from varying grades of malnutrition. The combined effect of malnutrition and non-insulin dependent diabetes (NIDDM) on the drug metabolising enzyme system has been evaluated using antipyrine as a protodrug. All the patients were under treatment and their plasma glucose values were within normal limits. The AUC of antipyrine was similar in all the groups. Although none of the kinetic parameters was altered in normal diabetics, the clearance of antipyrine was decreased and its half life was prolonged, with an increase in volume of distribution, in undernourished diabetics compared to undernourished controls. The results indicate that diabetes per se may not influence antipyrine kinetics when the blood glucose is well under control, but in the presence of undernutrition, it significantly alters the disposition of the drug.
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  • 98
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    European journal of clinical pharmacology 43 (1992), S. 567-569 
    ISSN: 1432-1041
    Keywords: Mefloquine ; Tetracycline ; Thai subjects ; Thai subjects ; drug interaction ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single oral dose of mefloquine given either alone or with tetracycline has been studied in 20 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with tetracycline (1600 vs 1160 ng · ml−1), as well as a significantly reduced terminal half-life (14.4 vs 19.3 days), mean residence time (11.9 vs 16.0 days) and volume of distribution at steady state (13.3 vs 19.91 · kg−1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 7 days was significantly increased by tetracycline (6.18 vs 4.76 μg · ml−1 · day). The changes in mefloquine disposition after tetracycline treatment are probably due to a reduction in enterohepatic recycling. The initial increase in mefloquine AUC without an apparent increase in side-effects suggests that this combination may have a place in the treatment of multi-drug resistant falciparum malaria.
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  • 99
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    European journal of clinical pharmacology 41 (1991), S. 379-382 
    ISSN: 1432-1041
    Keywords: Codeine ; paracetamol ; codeine-6-glucuronide ; pharmacokinetics ; metabolism ; partial clearance ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and urine concentrations of codeine and its measurable metabolites were determined by HPLC in six healthy subjects after a single 30 mg oral dose of codeine either alone or after 7 doses of 1 g paracetamol 8 hourly. After codeine alone, the t1/2 (h), AUC (μmol·l−1·h) and CLR (ml·min−1) for codeine were 2.2, 0.81, and 252 respectively. These were not significantly altered by paracetamol: 2.2, 0.84, and 291 respectively. For codeine-6-glucuronide the values were 2.4, 22.0, and 29.7 respectively. These were not significantly different from those after codeine plus paracetamol: 2.4, 21.9, and 39.6. There were no significant differences between the two treatments in the apparent partial clearances (ml·min−1) of codeine to morphine (88 codeine alone, 70 codeine plus paracetamol), to norcodeine (71 codeine alone, 88 codeine plus paracetamol), and to codeine-6-glucoronide (820 codeine alone, 1022 codeine plus paracetamol). The urinary excretion of codeine-6-glucuronide, morphine, norcodeine, and codeine were not significantly different between the two treatments.
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  • 100
    ISSN: 1432-1041
    Keywords: Cyclosporine ; Hyperlipidaemia ; heart transplantation ; fenofibrate ; fenofibric acid ; pharmacokinetics ; drug interaction ; nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cyclosporine (Cy) binds to lipoproteins in plasma. In order to test if its pharmacokinetics would be modified when efficient lipid-lowering treatment is introduced, a study has been done of Cy pharmacokinetics and any interaction with the lipid-lowering agent fenofibrate in hyperlipidaemic long-term, survivors of heart transplantation. Fenofibrate 200 mg once daily significantly reduced blood lipids (cholesterol 6.5 vs 7.7 mmol/l; apoprotein B 1.2 vs 1.6 g/l) but did not modify mean whole blood Cy trough levels (113 before fenofibrate vs 103 ng·ml−1), Cmax (812 ng·ml−1 by RIA and 757 ng·ml−1 by HPLC before fenofibrate versus 865 and 741 respectively, during fenofibrate); tmax (1.6 and 1.7 h before fenofibrate versus 1.4 and 1.4 h respectively), and t1/2 (13.9 and 11.1 h versus 9.5 and 10.7 h). The only adverse effect was an increase in creatinine (157 vs 145 mmol/l). Further studies are needed to investigate the mechanism of Cy-fenofibrate nephrotoxicity and to evaluate the long-term efficiency and safety of fenofibrate after heart transplantation.
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