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  • Articles  (106)
  • theophylline  (57)
  • Scolytidae  (49)
  • Springer  (106)
  • American Geophysical Union (AGU)
  • Annual Reviews
  • 1980-1984  (106)
  • 1935-1939
  • Chemistry and Pharmacology  (106)
  • Ethnic Sciences
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  • Articles  (106)
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  • Springer  (106)
  • American Geophysical Union (AGU)
  • Annual Reviews
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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of diuretics and methylxanthines in the neonate (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 55-63 
    Details
    ISSN: 1432-1041
    Keywords: diuretics ; furosemide ; caffeine ; theophylline ; neonate ; pharmacokinetics ; disposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elimination of diuretics and methylxanthines is considerably slower in the neonate than in the adult. Dose guidelines, especially during long term maintenance, must be adjusted to account for this slower drug elimination. Pharmacokinetic studies and the requisite pharmacologic evaluation on diuretics such as hydrochlorothiazide, spironolactone, ethacrynic acid and others should be done. Furosemide undergoes biotransformation in the newborn producing an acid metabolite and a glucuronide conjugate. Methylxanthines are effective in the treatment of neonatal apnea. Plasma elimination of theophylline is exceedingly slow, more so with caffeine. Decreased elimination is partly explained by decreased oxidative biotransformation. Caffeine is excreted in the urine of the newborn mainly unchanged (85%) in contrast to the adult where caffeine is a minor portion of urinary excretion (2%). Theophylline is methylated to caffeine and may possibly exert additive pharmacologic effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561479
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  • 2
    Electronic Resource
    Electronic Resource
    Disposition and clinical pharmacokinetics of theophylline after administration of a new sustained release tablet (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 39-44 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; sustained release tablet ; absolute bioavailability ; pharmacokinetics ; individual dosage regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic disposition of theophylline after taking a new, sustained release tablet (Theolair Retard® 250 mg, Theolair S. R.®, Riker Laboratories) has been studied in 8 hospitalized patients. Absolute bioavailability was determined from the ratios of the areas under the serum concentration-time curves after intake of the tablet and after intravenous infusion of aminophylline in the same patient. The absolute bioavailability of Theolair Retard® 250 mg was 110.9±20.8% (mean ± SD). Maximal serum concentrations were reached after 7.3±3.5 h, the large intersubject variation being due to differences in gastric emptying time. The tablets appear to release theophylline slowly in acid conditions, but more rapidly in an alkaline medium. Invasion was found to be either monophasic with a rate constant of about 0.8 h−1 (intestine), or biphasic with rate constants of 0.2 h−1 (stomach) and 0.8 h−1 (intestine). The peak levels accounted for 7.9±2.2 mg · 1−1. The profiles of the serum concentration-time curves were such that the concentrations remained above 80% of cmax for 6.5±3.3 h. The relevant pharmacokinetic parameters (half-life of elimination, total body clearance and volume of distribution) were determined and were used to calculate the individual dosage regimens required to obtain therapeutic serum concentrations. The optimal dosing interval to obtain an average steady state serum concentration of 12.5 mg · l−1 was 9.8±3.1 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609586
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  • 3
    Electronic Resource
    Electronic Resource
    Increase in plasma free fatty acids and natriuresis by xanthines may reflect adenosine antagonism (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 33-38 
    Details
    ISSN: 1432-1041
    Keywords: adenosine antagonism ; xanthines ; theophylline ; enprofylline ; free fatty acids ; natriuresis ; catecholamines ; renin ; insulin ; glucagons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The hypothesis has been examined that adenosine is involved in the diuretic and free fatty acid (FFA) — releasing action of xanthines. The effects of theophylline (T), a potent adenosine antagonist, were compared with those of enprofylline (3-propyl xanthine, E), which exerts negligible antagonism of adenosine. Eight healthy male volunteers were given E 1.5 mg/kg, T 5.0mg/kg or placebo 0.9% saline (P) intravenously in a double-blind, randomized, cross-over investigation. Blood samples were analyzed for E, T, catecholamines (CA: adrenaline, noradrenaline and dopamine), FFA, renin, glucose, glucagon and insulin, and urine was collected at 2-h intervals. T (plasma concentration 53±8 µmol/l) but not E (11±2 µmol/l) caused an increase in FFA from 0.42 to 0.86 mmol/l after 90 min. Without affecting the urinary excretion of potassium, T doubled natriuresis and the urine volume as compared to E and P. Neither T nor E had any effect on plasma CA, or on any other of the metabolic parameters studied. E, but not T, produced a small but statistically significant decrease in diastolic blood pressure (5 mmHg) and an increase in heart rate (3 beats/min). It is suggested that the difference between E and T in terms of stimulation of FFA-release and natriuresis may be related to their different ability to antagonize adenosine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546705
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  • 4
    Electronic Resource
    Electronic Resource
    Differential effects of cimetidine on theophylline metabolic pathways (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 335-340 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; cimetidine ; drug metabolism ; drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of cimetidine (1 g/day) on theophylline disposition and metabolism were examined in smokers and non-smokers for single dose intravenous and chronic oral administration of theophylline. In the intravenous study the effect of cimetidine on plasma theophylline clearance was more marked in smokers (22.7% reduction) than in non-smokers (12.2% reduction). Similarly, in the multiple dose study the effect of cimetidine on theophylline clearance was greater in smokers (28.3% decrease) than in non-smokers (11.3% decrease). The reduction in clearance was largely due to a reduction in metabolic clearances by 3-demethylation (Cl3DM) and 1-demethylation (Cl1DM) with no significant effect on clearance by 8-oxidation (Cl80X). There was a strong correlation between Cl3DM and Cl1DM (r=0.98, p〈0.001) in both control and cimetidine study phases, whereas other correlations between partial clearances were less marked and were not apparent during the cimetidine phase. The results are consistent with the view that 1- and 3-demethylation of theophylline are carried out by a common form of cytochrome P-450 which is selectively induced by cigarette smoking and preferentially inhibited by cimetidine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548764
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  • 5
    Electronic Resource
    Electronic Resource
    Comparative pharmacokinetic analysis of a novel sustained-release dosage form of theophylline in humans (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 401-403 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; serum concentration ; sustained-release dosage form
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and relative bioavailability of theophylline from a new sustained-release formulation (Theotard®) and from a standard sustained-release formulation (Theo-Dur®) were compared in 6 healthy, adult, male volunteers. After a single oral dose of 300 mg Theotard, a mean maximal plasma concentration (Cbmax of 3.49±1.05 mg/l was obtained after 8 h (tmax). After an identical dose of Theo-Dur, a peak plasma concentration of 4.68±1.33 mg/l was obtained after 6.33 h. The mean relative bioavailability of theophylline from Theotard was 1.02±0.16 relative to that of Theo-Dur. In 5 of the volunteers the Theotard formulation exhibited a more prolonged and uniform absorption rate and yielded more sustained plasma levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548775
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  • 6
    Electronic Resource
    Electronic Resource
    Protective effect of oral oxyphenonium bromide, terbutaline and theophylline against the bronchial obstructive effects of inhaled histamine, acetylcholine and propranolol (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 435-441 
    Details
    ISSN: 1432-1041
    Keywords: airway reactivity ; oxyphenonium bromide ; terbutaline ; theophylline ; asthmatic patients ; inhalation ; provocation test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protective effects of oxyphenonium bromide, terbutaline and theophylline were compared in 8 asthmatic patients by determination of the degree of non-specific airway reactivity after 1 week of oral treatment according to a fixed dose scheme in a double-blind random order: oxyphenonium bromide 3×10 mg; terbutaline 3×5 mg; theophylline 2×300 mg and placebo. Controlled, standardized inhalation provocation tests were carried out with histamine, acetylcholine and propranolol. The study was monitored by measuring blood concentrations of the 3 drugs, and their effect on the plasma cAMP concentration was also determined. Significant protection by oxyphenonium bromide against the bronchial obstructive effects of acetylcholine and propranolol was observed, but not against the effect of inhaled histamine. The other two drugs provided no significant protection against the inhaled agents. The absence of any protective effect of terbutaline and theophylline might have resulted from too low a blood concentration. The observed differences in protection could not be explained by changes in pulmonary function. The study suggests dissociation between the bronchodilating effect of a drug and its protective effect against inhaled substances.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542137
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  • 7
    Electronic Resource
    Electronic Resource
    Lack of dose dependent kinetics of theophylline (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 525-527 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; airway obstruction ; biotransformation ; kinetics ; oral dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Oral theophylline was given to 6 adults with airways obstruction. The initial dose was 125 mg daily and this was increased by 125 mg each week. The final total daily dose reached was determined by side effects and ranged from 500 mg to 1125 mg. At the end of each week and before the next dosage increment steady state, trough plasma theophylline concentrations were measured. For each individual and for the group as a whole there was a highly significant linear correlation between theophylline dose and trough plasma concentration. This indicates that for oral theophylline, in adults, dose-dependent kinetics do not play a significant role and dose may be adjusted without fear of a disproportionate rise in plasma concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609897
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  • 8
    Electronic Resource
    Electronic Resource
    Disposition and clinical pharmacokinetics of microcrystalline theophylline (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 379-384 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; obstructive lung disease ; microcrystalline ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1−1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558452
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  • 9
    Electronic Resource
    Electronic Resource
    A hand-held calculator program for individualized dosage adjustment of intravenous theophylline in acute asthma (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 393-399 
    Details
    ISSN: 1432-1041
    Keywords: asthma ; theophylline ; dosage calculations ; dosage adjustment ; hand-held calculator programs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Despite general development of drug assay services and increasing interest in pharmacokinetics, proper dosage regimen calculations are not often made in routine clinical practice. This could be due, in part, to unfamiliarity with pharmacokinetic theory, the consequent difficulty of collaboration and the inevitable delay while data are processed on a computer. The present program for a hand-held calculator (TI-59) was written to minimize these problems, and was designed for the use of intravenous theophylline in the management of acute asthma, where there is a need for individualisation of dosage. Calculations are based on the one compartment open model. With 3–4 plasma drug concentrations taken early in the treatment, the program gives a measure of goodness of fit, the elimination rate constant (kel), the volume of distribution (Vd) and the suggested infusion rate to achieve a given steady-state level. Data from 10 severe acute asthmatic patients were used to test the model and the estimated parameters were: Vd=0.26±0.029 l/kg (mean±SEM) and kel=0.20±0.045 h−1. The average standard deviation (s) for differences between the model and observations was 0.96±0.21 mg/l, of which at least 0.5 mg/l was due to assay error. In seven patients where the infusion period was extended, the predicted steady state plasma concentration agreed reasonably with that observed (r=0.83, df=5, 0.01〈p〈0.05).
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    URL: http://dx.doi.org/10.1007/BF00558454
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  • 10
    Electronic Resource
    Electronic Resource
    Correlation of serum and saliva theophylline concentrations after administration of a sustained release preparation (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 73-78 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; sustained release preparation ; serum level ; saliva level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The correlation between serum and saliva levels of theophylline was investigated in seven healthy volunteers after multiple dose administration of a low dose (300 mg/day) and a high dose (900 mg/day) of a sustained release theophylline preparation (Theo-Dur®). Tablets were taken for five days, at 8 a.m. and 8 p.m. and a last dose was taken on Day 6 at 8 a. m. Fourteen serum and saliva samples were collected simultaneously during the dosing period and for up to 32 h after the last dose. On the 300 mg/day regimen the level in saliva was 55.3% of the serum level, with an overall variability of 6.7% and an intrasubject variability of 10.5%. After 900 mg/day, the saliva concentration was 55.5% of the serum concentration, with an overall variability of 7.6% and an intrasubject variability of 12.7%. A good correlation was found between both determinations (r=0.99), which suggests that saliva levels could be used to monitor theophylline after administration of a sustained release tablet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00554670
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  • 11
    Electronic Resource
    Electronic Resource
    Influence of food intake on bioavailability of theophylline in premature infants (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 171-173 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; neonates ; bioavailability ; food intake ; premature infants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 16 premature infants suffering from neonatal apnoea received orally an aqueous solution of theophylline 5 mg/kg bodyweight under fasting conditions and immediately before a milk feed. Bioavailability up to 7 h after administration was determined from the serum concentration-time course. The rate of absorption was significantly decreased if the drug was given with food; mean maximum serum concentrations were reached after 4.7 h instead of 1.6 h under fasting conditions. The area under the curve did not differ between the two patient groups which indicates that only the rate but not the amount of absorption was affected by food intake. The influence of feeding on the rate of absorption of theophylline by premature infants, which is more pronounced than in adults, can be related to particular functional factors in the gastrointestinal tract during the neonatal period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542463
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  • 12
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of theophylline in Ethiopian children of differing nutritional status (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 89-92 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; kwashiorkor ; marasmus ; children ; nutritional status ; pharmacokinetics ; dosage recommendation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of theophylline in Ethiopian children of differing nutritional status was studied. In 8 children of normal weight, the t1/2β (4.93 h) plasma clearance (1.22 ml/min/kg and Vd area (504 ml/kg) were similar to those of Swedish children of normal weight. In children with marasmus or kwashiorkor there was an increased volume of distribution. The increase in Vd was reflected in an increased biological half-life, in spite of a slight but not significant increase in clearance in both of these groups of children. The pharmacokinetic changes in clearance and volume of distribution found in malnutrition should counteract each other, so from a clinical point of view theophylline can be given to Ethiopian children according to the standard dosage recommendation, regardless of nutritional status.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613932
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  • 13
    Electronic Resource
    Electronic Resource
    Bioavailability and pharmacokinetics of theophylline in plain uncoated and sustained-release dosage forms in relation to smoking habit I. Single dose study (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 79-87 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; smoking habit ; absolute bioavailability ; pharmacokinetics ; sustained release preparation ; plain tablet preparation ; antipyrine pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of theophylline from a plain uncoated and 2 newly designed, sustained-release tablet formulations, as compared to intravenous aminophylline, were studied in 12 healthy adult male volunteers. The subjects were divided into two groups (n=6) with respect to smoking habit and on 4 separate occasions each received, on a randomized cross-over basis, a single dose of 400 mg equivalent of theophylline from every dosage form. The intravenous aminophylline study showed that habitual smoking had a significant (p〈0.05) effect on plasma theophylline clearance (0.051±0.006 vs 0.035±0.004 l/kg/h). Smoking significantly reduced the raw AUC from the 4 dosage forms (p〈0.05), but did not change the characteristics of absorption of each formulation. There was a non-significant trend towards reduced absolute bioavailability of theophylline from sustained-release formulations in smokers (percentage mean difference — 16% for one formulation and 13% for another). The trend was not observed for the plain uncoated tablet, which was rapidly absorbed (p〈0.01 to 0.05 in Ka, tmax and Cmax compared to sustained-release tablets). Similarity of the in vitro dissolution profiles of the two sustained-release formulations did not imply similarity of the in vivo absorption characteristics. Plasma clearances of theophylline and antipyrine were significantly correlated (p〈0.05,r=0.693,n=10). Thus, smoking enhanced the elimination of theophylline regardless of the dosage form administered. However, the extent to which habitual smoking may affect the hepatic first-pass effect on theophylline from sustained-release formulations requires further study. The results also suggest that theophylline and antipyrine may share a similar or common and presumably polycyclic hydrocarbon-inducible form(s) of microsomal drugmetabolizing enzyme.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613931
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  • 14
    Electronic Resource
    Electronic Resource
    Enhanced prostacyclin production by dipyridamole in man (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 9-15 
    Details
    ISSN: 1432-1041
    Keywords: dipyridamole ; prostacyclin ; phosphodiesterase inhibitors ; theophylline ; antiaggregating agents ; ischaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of some phosphodiesterase (PDE) inhibitors (dipyridamole, theophylline, papaverine and SH-869) on prostacyclin (PGI2) production have been studied in vitro and in vivo. PGI2 was bioassayed by Vane's superfusion technique. In rabbit aortic rings, only dipyridamole in concentrations from 1 to 12 µM was able to stimulate PGI2 biosynthesis in a dose-dependent manner. This effect was also detected with so-called “exhausted” rabbit aortic rings. The other PDE inhibitors used, both in µM and mM concentration, did not affect PGI2 biosynthesis. Dipyridamole was found to increase PGI2 production in healthy volunteers, when given both by infusion (8 µg/kg/min × 2 h) and by oral administration (375 mg/day for seven days). Circulating PGI2 and PGI2 production induced by a 3-min period of ischaemia were increased by an average of 137% (p〈0.001) and 30.8% (p〈0.001) respectively. Saline and theophylline (as aminophylline) infusions used as controls did not affect PGI2 production.
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    URL: http://dx.doi.org/10.1007/BF00609581
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  • 15
    Electronic Resource
    Electronic Resource
    Food does not effect in bioavailability of theophylline from Theolin Retard® (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 405-407 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; drug absorption ; bioavailability ; food intake ; sustained-release preparations ; Theolin Retard
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of theophylline from a sustained release tablet preparation (Theolin® Retard 300 mg) was studied in 10 subjects both when fasting and immediately after a standardized breakfast. Intravenous aminophylline was used as the reference material. Food did not influence the absorption from Theolin Retard. The bioavailability was complete (93% after 30 h) both with and without food, and no difference was found in the time to peak of the plasma concentration curve (7 h), or the mean residence time (14 h). The absorption characteristics, with predominantly zero order kinetics, did not change with concomitant intake of breakfast.
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    URL: http://dx.doi.org/10.1007/BF00548776
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  • 16
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    Electronic Resource
    The disposition of inhaled lysine theophylline in volunteers (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 635-637 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; inhalation ; saliva-serum distribution ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy volunteers received an iv infusion of 317 mg lysine theophylline (equivalent to 197 mg anhydrous theophylline) in order to calculate theophylline clearance by standard methods. They subsequently received a 20 minute inhalation of nebulised lysine theophylline. Serum and salivary theophylline concentrations were measured and all saliva was collected for the first hour. From these concentrations estimates were made of the distribution of theophylline into the blood and saliva with 40% to 94% identified in the blood. Very high salivary concentrations were reached during the inhalation phase with saliva: serum concentration ratios of between 60 and 1600.
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    URL: http://dx.doi.org/10.1007/BF00543500
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  • 17
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    Intravenous administration of enprofylline to asthmatic patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 323-327 
    Details
    ISSN: 1432-1041
    Keywords: enprofylline ; theophylline ; constant infusion ; bronchodilator effect ; adverse reactions ; pharmacokinetics ; asthmatic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 6 asthmatic patients, the possibility of obtaining a steady state plasma level of 5 mg/l of enprofylline by administration of two constant rate infusions was examined. The simulated plasma concentration curves, based on information from pressessment of individual pharmacokinetic parameters, were in good agreement with the plasma levels obtained. The side-effects and bronchodilatation produced by enprofylline were compared to those obtained with theophylline at a steady state level of 15 mg/l. Enprofylline and theophylline caused a mean maximal increase in FEV1.0 of 14% and 2.6% per mg/l in plasma, respectively. Side-effects, head-ache, nausea and vomiting, became pronounced in 2 patients in whom the plasma enprofylline level was about 6 mg/l. No other serious adverse reaction was seen. It is suggested that enprofylline should be further evaluated as a possible anti-asthmatic drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610048
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  • 18
    Electronic Resource
    Electronic Resource
    Use of single doses and rapid sampling to detect interactions with cimetidine (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 603-606 
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    ISSN: 1432-1041
    Keywords: cimetidine ; theophylline ; drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this study the well-established interaction between cimetidine and theophylline has been demonstrated using only a single dose of cimetidine. Eleven healthy subjects were given a 30 min infusion of theophylline on two separate occasions and plasma levels were monitored at frequent intervals. During one of the studies, a single 400 mg oral dose of cimetidine was given after collection of the 3 h sample. After normalisation of the control and test curves, a deflection was apparent in the test theophylline elimination curve in 9 out of 11 subjects. This method may provide a rapid screening method to detect such interactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00556899
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  • 19
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    The influence of theophylline on maximal response to salbutamol in severe chronic obstructive pulmonary disease (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 389-393 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; salbutamol ; bronchitis ; maximal response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have previously shown that inhaled salbutamol further increases the bronchodilator response after the maximum effect of theophylline has been obtained in patients with severe chronic bronchitis. We now report the results of adding maximally effective doses of theophylline to the maximum response obtainable from salbutamol in ten of these patients. We constructed dose response curves to ensure maximum possible effect from salbutamol. Response plateaus (in nine out of ten patients) were achieved with cumulative doses of between 200 µg and 3,000 µg salbutamol and there was a significant response (p〈0.05) in every subject: the mean FVC response was 1.1 l (ranging from 0.5 to 1.8 l) and the mean FEV1 response was 0.4 l (ranging from 0.1 to 0.8 l). Theophylline, in their previously determined maximally effective doses, produced statistically significant (p〈0.05) small further increases in both FVC (0.2 to 0.6 l) and FEV1 (0.1 to 0.6 l) in four patients only. The other six did not respond. In patients classified as chronic bronchitics there is clearly a wide variation in response to bronchodilators and a surprising degree of reversibility can be achieved. But because of this variation in response, conventional drug doses may be too small in some cases. Ideally, each bronchodilator should be prescribed after some form of individual dose response studies. Although this acute study shows little or no benefit in the height of the bronchodilator response the usefulness of this combination can only really be decided after similar studies including the duration of effect in long term administration.
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    Pharmacokinetics of theophylline in infants with bronchiolitis (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 123-127 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; bronchiolitis ; infants ; pharmacokinetics ; single dose ; multiple doses ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Theophylline pharmacokinetics were studied in 12 infants (age 3 weeks–6.5 months) with bronchiolitis. 9 of the 12 patients received a single dose of aminophylline (5.0–8.5 mg/kg) whereas the remainder were at steady-state receiving multiple doses (2.5–5.0 mg/kg) of aminophylline. The dose was administered IV over 0.5–1.0 h. An HPLC method was used to measure theophylline concentrations in serum and urine. Peak serum concentrations of theophylline measured by HPLC ranged from 8.48–21.6 µg/ml. Total, renal and nonrenal clearance of theophylline ranged from 4.66 to 19.25, 1.07 to 5.76 and 3.59 to 16.83 ml/min/m2, respectively. Mean apparent volume of distribution and elimination half-life were 8.75 l/m2 and 11.38 h, respectively. Although no significant correlation was observed between age and theophylline kinetic parameters, clearance appeared to increase and half-life decrease with age. Our patients had a substantially lower clearance and longer half-life as compared to published data in children 〉1 year of age. A five-fold variation in theophylline clearance demonstrates the need for monitoring theophylline serum concentration to minimize the risk of potential toxicity.
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    Effect of chronic oral contraceptive steroids on theophylline disposition (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 129-134 
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    ISSN: 1432-1041
    Keywords: theophylline ; ethinylestradiol ; oral contraceptives ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of chronic oral contraceptive (OC) usage on the disposition of theophylline was examined. Aminophylline solution (4 mg/kg) was given orally to 8 healthy female non-OC users and to 8 healthy women who were chronic (〉6 months) OC users. The OC user group had a significantly lower total plasma clearance of theophylline than women not using OC (35.1±5.6 vs. 53.1±14.5 ml/h/kg). The t1/2 was also significantly prolonged in the OC group (9.79±1.43 vs. 7.34±1.75 h) while the volume of distribution was similar between the 2 groups. The serum ethinylestradiol (EE) concentrations after oral OC administration were measured simultaneously. The apparent clearance of EE was about 30% lower in the OC users. A significant positive correlation was found between the apparent clearance of EE and the plasma clearance of theophylline. The effects of OC are predominantly due to chronic use with decreased elimination of both theophylline and EE.
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    Measurement of excretion characteristics of theophylline and its major metabolites (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 435-441 
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    ISSN: 1432-1041
    Keywords: theophylline ; renal excretion ; metabolite formation ; capacity-limited kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Analysis of urinary excretion after administration of 320 mg of theophylline to six normal volunteers appears to indicate the occurrence of capacity limited formation of most of the theophylline metabolites and non-linear renal excretion of theophylline. The renal clearance is elevated at high concentrations where the metabolic clearance is reduced. Even though the individual process of elimination is non-linear, the compensating relationship appears to yield a constant total elimination clearance. The implication of these results in chronic therapy and dose adjustment is discussed.
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    A comparison of the pharmacokinetics of theophylline in asthmatic children in the acute episode and in remission (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 443-447 
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    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; children ; acute episode ; remission ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of theophylline following a single intravenous dose of aminophylline were determined in 8 asthmatic patients in each of the acute, the recovery and the remission phases. The overall results for mean plasma theophylline clearance (78.6±33.3 ml/kg/h), plasma theophylline half-life (4.14±1.36 h) and apparent volume of distribution (0.41±0.066 l/kg) are in accordance with previously published values. There was no general statistically significant difference in any of the pharmacokinetic parameters when results from the acute and remission phases were compared. However, certain patients showed reductions in plasma theophylline clearance in the acute phase of the illness such that a dosage regimen standardised during remission may cause toxicity if continued in the acute episode. It is suggested that monitoring the plasma theophylline levels is desirable in all patients in the acute episode.
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    Serum theophylline levels after use of an anhydrous crystalline theophylline suppository (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 449-452 
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    ISSN: 1432-1041
    Keywords: theophylline ; ethylenediamine ; suppository ; serum concentration ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of theophylline from a suppository not containing ethylenediamine was tested in 9 healthy volunteers. AUC after rectal administration of anhydrous crystalline theophylline 250 mg (AUCrectal) was compared with the AUC after oral administration of microcrystalline theophylline 250 mg (Nuelin®; AUCoral) in a randomized, cross-over study. The ratio AUCrectal/AUCoral was 0.75 at 10 h, and the ratio AUCrectal×βrectal/AUCoral×βoral extrapolated to infinite time was 0.83. A mean concentration of 5.7 µg/ml was reached 3.7 h after a single rectal dose. The absorption studies were performed with suppositories stored for 15 weeks at 22 °C. No effect on the in vitro release rate of theophylline from the suppository was observed during storage at room temperature from 3 to 31 weeks after production. Since aminophylline suppositories are known to decompose upon storage, the results suggest that a formulation without ethylenediamine is preferable for the rectal administration of theophylline.
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    Sustained serum theophylline concentrations during chronic twice daily administration of a slow release preparation (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 205-208 
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    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; slow release theophylline ; reversible obstructive airways disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Theophylline concentrations were measured in a clinical setting in 15 patients given a slow release theophylline preparation (Theo-Dur) every 12 h for reversible obstructive airways disease. Doses of 300–600 mg (464±134), 12 hourly, resulted in mean serum concentrations which increased from 11.2±2.9 µg/ml at 0 h to a peak of 15.5±4.6 µg/ml at 6 h and decreased again to 10.4±2.9 µg/ml at 12 h. The mean percentage fluctuation of serum concentrations (maximum minus minimum expressed as a % of the maximum) was 38.6±10.1%, range 20.3% to 54.9%. There was a significant positive correlation between % fluctuation and theophylline steady-state clearance determinations. Excluding a single heavy smoker, theophylline clearance also showed a significant inverse relationship with age. These data suggest that when this slow release preparation is given 12 hourly, satisfactorily sustained serum theophylline concentrations will be achieved in most adults.
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    Aging, cigarette smoking and oral theophylline requirement (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 33-37 
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    ISSN: 1432-1041
    Keywords: theophylline ; aging ; cigarette smoking ; obstructive pulmonary disease ; plasma levels ; steady-state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a prospective study in 73 patients with obstructive pulmonary disease, aged 63.5±13.5 years (SD), it was found that theophylline dose, cigarette smoking and age were all significant determinants of the steady-state trough plasma theophylline level during oral administration of the drug. As the predictive efficiency of the three factors combined amounted only to 25%, firm dosage recommendations cannot be made. Even among elderly patients, tobacco smokers had significantly lower plasma concentrations of theophylline. It is suggested that in order to obtain trough plasma concentrations of 50 µmol/l (≈9 µg/ml), a non-smoking 50 year-old patient would require 9.8 mg/kg/day of oral theophylline, the dose increasing to 14.2 mg/kg/day in smokers of the same age. These doses should probably be reduced by 15–20% in 75 year-old patients.
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    Cardiovascular effects of theophylline (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 109-114 
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    ISSN: 1432-1041
    Keywords: theophylline ; beta-blocker ; asthma ; arterial blood pressure ; inotropism ; heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of theophylline upon cardiovascular function were studied in 8 male subjects, aged 22–33 years, before and during concomitant administration of metoprolol (50 mg every 6 h) and propranolol (40 mg every 6 h). Theophylline, as aminophylline (6.7–7.3 mg/kg) was given over 30 min. The theophylline level five minutes after completion of the aminophylline infusion was 15.9±1.8 µg/ml in the absence of beta blockade, 16.1±1.7 µg/ml during metoprolol, and 15.1±1.6 µg/ml during propranolol. Theophylline produced a 7% increase in mean arterial pressure which was not attenuated by either metoprolol or propranolol. Heart rate was not changed by theophylline. The QS2 Index (QS2I), a sensitive indicator of inotropism, was shortened from 488±16 to 476±16 msec (p〈0.01) by theophylline alone. After administration of metoprolol or propranolol, theophylline produced no shortening of the QS2I. Theophylline has a mild inotropic effect in healthy subjects. This effect is prevented by pretreatment with beta-adrenergic antagonists.
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    Bioavailability and diurnal variation in absorption of sustained release theophylline in asthmatic children (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 667-672 
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    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; children ; sustained-release ; diurnal ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absolute oral bioavailability of a sustained release theophylline tablet (Nuelin-SR250), given 12 hourly was determined in 14 asthmatic children aged 5 to 13 years. In 4 of the patients, mean bioavailability of the fourth dose was 38.9±8.4% and that of the sixth dose was 67.9±25.9% (p〈0.05) in the other ten patients. This suggests steady-state had not been achieved after four doses. In the initial study with 9 patients, a significant diurnal variation in predose plasma theophylline concentrations was observed, as the mean morning predose concentrations were 2.9 fold greater than the mean evening predose concentrations (p〈0.005). Dual peak plasma concentrations occurred in 5 out of the 9 patients. The mechanism of this diurnal variation was investigated in a further 5 asthmatic children (10.8 years ±1.6). Morning and night steady-state plasma theophylline concentrations during a continuous intravenous infusion of aminophylline were not different (14.9±5.3 mg/l vs. 15.6±5.9 mg/l), demonstrating that there was no diurnal variation in the plasma clearance of theophylline. The diurnal variation in predose concentrations with Neulin-SR250 was confirmed with the morning concentrations again being 2.6 fold greater than those in the evening. However, bioavailability was not significantly different for day (09.00–21.00) and night (21.00–09.00) dosing intervals after doses 6 and 7 respectively of Nuelin-SR250. The plasma concentration versus time profiles suggested that the diurnal variation in predose concentrations was due to slower absorption of the evening dose.
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    Theophylline antagonizes diazepam-induced psychomotor impairment (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 743-747 
    Details
    ISSN: 1432-1041
    Keywords: diazepam ; theophylline ; psychomotor performance ; Clyde Mood Scale ; State Anxiety Inventory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight healthy men received an oral dose of 0.25 mg/kg diazepam followed 40 min later by an intravenous infusion of 100 ml physiological sodium chloride solution, with or without 4.4 mg/kg theophylline. Psychomotor function was assessed after each blood sampling up to 5 h post-infusion. Thirty min after diazepam psychomotor performance measured by Card Sorting test and Digit Symbol Substitution test was impaired and subjects felt sleepy and could think less clearly (two factors of the Clyde Mood Scale). Theophylline antagonized the diazepam-induced impairment statistically significantly for up to 5 h and subjects felt less tense and less apprehensive (State Anxiety Inventory). Since pharmacokinetic parameters of diazepam seemed not to be different after theophylline, interaction at receptor level can be assumed.
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    Chronopharmacokinetics of theophylline after sustained release and intravenous administration to adults (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 215-222 
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    ISSN: 1432-1041
    Keywords: theophylline ; chronopharmacokinetics ; sustained release tablet ; intravenous administration ; absolute bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of time of drug administration on pharmacokinetics of theophylline was studied both after ingestion of a sustained-release tablet, containing choline theophyllinate (Zy 15061-S. R.; Teovent®; Sabidal®; ZYMA S.A.) and after intravenous infusion of aminophylline to eight healthy volunteers. Both drugs were administered in the morning (10 a.m.) and on a separate occasion in the evening (10 p.m.) after a 12 h period of fasting. After oral administration of a dose of 540 mg theophylline, the drug was steadily absorbed, both during day-time and during night-time. In some subjects absorption was slower in the evening. Maximum theophylline plasma concentrations were reached after 3.3±0.4 h (mean±SD) and 3.9±1.4 h respectively (not significantly differentp〉0.05). The maximum plasma concentrations were almost identical after administration in the morning and in the evening (12.6±3.3 mg·l−1 and 13.1±1.4 mg·l−1 respectively). There was also no significant difference (p〉0.05) between the areas under the plasma concentration-time curves after oral and intravenous administration, both at day-time and at night-time. This finding indicates complete bioavailability of the sustained release tablets on both occasions. After administration of the tablets in the morning the plasma concentration 12 h post dosing was significantly lower than after administration in the evening: c 12 1 accounted for 6.0±2.0 mg·l−1 after intake at 10 a.m. and for 7.9±2.1 mg·l−1 after ingestion at 10 p.m. (p〈0.01). A similar observation was done after intravenous administration of the drug: c12 was 6.6±1.6 mg·l−1 after starting the infusion in the morning and 8.0±1.8 mg·l−1 after infusing the drug in the evening (p〈0.01). This phenomenon could be explained by the finding of a significantly prolonged half-life of theophylline during night-time, provided that the plasma concentrations were in the range of 5 to 15 mg·l−1 (which coincides approximately with the therapeutic range of the drug). For day-time elimination the half-life of theophylline was found to be 6.2±0.9 h and for night-time elimination 8.0±2.0 h (p〈0.01), which means an increase of 29.6±20.9% during the night. The prolonged half-life of theophylline at night-time might be of therapeutic benefit in preventing bronchus obstruction in the morning.
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    Lack of clinically important interaction between erythromycin and theophylline (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 485-489 
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    ISSN: 1432-1041
    Keywords: theophylline ; erythromycin ; interaction ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 11 healthy volunteers the kinetics of theophylline and the plasma levels and the urinary excretion of its metabolites were studied before and after treatment with erythromycin for 10 days. Theophylline was administered as an intravenous bolus injection (280 mg) followed by a constant intravenous infusion (23.8±4.1 mg/h) for 6 hours. The total clearance of theophylline at steady-state (63.4±9.9 vs 63.8±14.4 ml/min, before vs after erythromycin treatment) and the elimination half-life after cessation of the infusion (6.7±2.6 vs 7.5±1.8 h, before vs after treatment) did not change during the treatment with erythromycin. No difference in the formation of metabolites before and after treatment with erythromycin was detected; the findings in urine were 40.4±5.0 vs 42.1±5.4% 1,3-dimethyluric acid, 29.6±4.6 vs 30.1±5.9% 1-methyluric acid and 13.4±3.5 vs 12.5±2.2% 3-methylxanthine before and after erythromycin treatment, respectively. It is concluded that a clinically relevant interaction between erythromycin and theophylline does not occur.
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    Plasma theophylline and caffeine and plasma clearance of theophylline during theophylline treatment in the first year of life (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 371-374 
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    ISSN: 1432-1041
    Keywords: theophylline ; caffeine ; apnoea ; aminophylline ; infant ; plasma level ; plasma clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of caffeine and theophylline were simultaneously determined in 17 preterm infants after oral administration of aminophylline for treatment of apnoea. The ratio of caffeine/theophylline concentration in plasma increased during the first 2 weeks of treatment, owing to the longer time required for caffeine than for theophylline to reach steady state. The caffeine/theophylline ratio at steady state was 0.57±0.03 (mean±SE). Thus, caffeine contributed significantly to the total methylxanthine load in the infants. The plasma clearance of theophylline was calculated from the plasma steady state concentrations. In 3 preterm infants treated with oral aminophylline, repeated sampling showed an approximately linear increase in clearance with time from 16.8±0.4 (mean±SE) at a postnatal age of 6–11 days to 30.9±2.5 ml/kg/h at 64–69 days. In 1 full-term infant treated with oral theophylline from 3.5 to 11.5 months of age, the plasma clearance of theophylline increased in a roughly linear manner, reaching a plateau of about 100 ml/kg/h at 6–7 months of age. This corresponds to the clearance found in 1–4 year old infants.
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    Protein binding of enprofylline (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 703-708 
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    ISSN: 1432-1041
    Keywords: enprofylline ; 3-propylxanthine ; protein binding ; equilibrium dialysis ; theophylline ; ultrafiltration ; pH effect ; species differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protein binding of enprofylline, 3-propylxanthine, in plasma was studied by equilibrium dialysis and ultrafiltration under various experimental conditions. A limited comparison with theophylline was also undertaken. The mean fraction of enprofylline bound in human plasma at 20°C was 47.3±1.1% (SD), which was only 2% less than theophylline. The binding of the two drugs increased dramatically in the pH range 7.2 to 7.8, as reported previously for theophylline. Reasonable agreement was found between equilibrium dialysis and ultrafiltration, but the latter technique proved impractical, because pH control was difficult to achieve. A pronounced species difference in the binding of enprofylline was found. At pH 7.4 an almost constant level of binding of 57% in dog and 81% in rat was found up to 2 · 10−5 M (approx. 4 mg/l). Corresponding values in human and monkey plasma were 47 and 48%, respectively, up to 10−4 M (approx. 20 mg/l).
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    Individualizing theophylline dosage: Evaluation of a single-point maintenance dose prediction method (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 491-498 
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    ISSN: 1432-1041
    Keywords: theophylline ; computer simulation ; pharmacokinetics ; single-point dose prediction ; nomogram
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dosage prediction method to estimate theophylline clearance and dose requirement was evaluated in 22 outpatients with partly reversible obstructive airways disease. The steady state theophylline dose required to achieve a target concentration (Css) was predicted using a single serum theophylline determination 8 h after a single oral test dose. In 17 nonsmoking patients a mean absolute deviation of 8.2% (range 0.0–21.7%) between predicted and observed Css was found, and in 5 smoking patients the mean deviation was 34.0% (range 2.2–53.8%). In 17 healthy smokers the single-point method was found to predict theophylline clearance at a sampling time of 8 h with a prediction error of 11.3 (range 0.8–25.3%) compared to the clearance determination using the area under the curve. In addition, a numerical simulation program to assess the influence of absorption, elimination and sampling time on predictive accuracy showed that the method could be successfully applied to a patient population with elimination rate constants between 0.07 1/h and 0.25 1/h, allowing a mean prediction error of 15%.
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    Comparison of oral enprofylline and theophylline in asthmatic patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 707-709 
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    ISSN: 1432-1041
    Keywords: enprofylline ; theophylline ; asthma ; clinical trial ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bronchodilator effect and side-effects of a single oral dose of enprofylline were compared with the corresponding actions of a therapeutic dose of theophylline in 20 asthmatic patients, in a randomized cross-over clinical trial. Enprofylline 4 mg/kg and theophylline 8 mg/kg produced mean maximum plasma levels of 4.40±0.91 µg/ml and 16.5± 2.58 µg/ml and mean maximum increases in FEV1.0 of 38.5% and 34.8%, respectively. The degree of headache and nausea was estimated by a scoring system. Enprofylline produced significantly higher scores for headache than theophylline, and both drugs produced s light nausea. No other side-effects were seen. Enprofylline seems to have bronchodilating properties comparable to those of theophylline without producing severe sideeffects.
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    Plasma concentration-effect relationship of theophylline in treatment of apnea in preterm infants (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 65-68 
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    ISSN: 1432-1041
    Keywords: apnea ; theophylline ; xanthines ; preterm infants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relation between plasma concentration of theophylline and number of apnea in preterm infants was studied in six patients. The apnea frequency was monitored after cessation of theophylline treatment and plotted against the log plasma concentration of theophylline. It was calculated that at an average plasma concentration of 40 µmol/l (7.25 µg/ml) the preterm infants had two or less apnea per 12 h. On the basis of our results we suggest that 40 µmol/l is the minimum plasma concentration of theophylline for optimal effect on apnea in preterm infants.
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    Effects of enprofylline, a xanthine lacking adenosine receptor antagonism, in patients with chronic obstructive lung disease (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 395-402 
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    ISSN: 1432-1041
    Keywords: enprofylline ; theophylline ; obstructive lung disease ; adenosine ; antagonism ; bronchodilatation ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Enprofylline, a xanthine-derivative shown experimentally to lack universal adenosine receptor antagonism, has been examined in patients with partly reversible, chronic, obstructive lung disease. Significant bronchodilation was produced by enprofylline 2 mg/kg, giving a peak plasma concentration of 3.0±0.6 µg/ml (mean ± SD). A dose of 2+4 mg/kg dilated the bronchi at least to the same extent as theophylline 9.2±0.9 mg/kg (plasma level 18.5±4.7 µg/ml). Neither at the low nor at the high dosage (2+4 mg/kg), giving plasma concentrations of 8.5±1.4 µg/ml, did enprofylline produce theophylline-like CNS effects, such as restlessness and tremor, but it did exhibit some of the innocuous side effects expected with xanthine derivatives, such as epigastric discomfort and headache. The comparison with theophylline was limited because different dosage forms had to be used (solution and tablets), which for example, resulted in different absorption rates. Nevertheless, the present findings indicate enprofylline to be a potent bronchodilator in patients with obstructive lung disease, suggesting that adenosine-receptor antagonism is not involved in the bronchodilator effects of xanthines.
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    Pharmacokinetics of theophylline in patients following short-term intravenous infusion (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 417-422 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; obstructive airways disease ; short-term i.v. infusion ; log-normal distribution ; pharmacokinetics ; serum concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum theophylline concentrations after intravenous administration of a new short-term infusion (Euphyllin® Kurzzeitinfusion) were measured in 50 out-patients with chronic obstructive airways disease (COAD). An intravenous infusion of theophylline ethylenediamine 480 mg (corresponding to approximately 350 mg anhydrous theophylline) in 50 ml isotonic solution was given in 20 min. Blood samples were taken beforehand and 25 to 30 min and 1, 3 and 6 h after starting the infusion. 86% of the patients had a one-hour serum level in the therapeutic range of 8–20 mg/l, and 2 h later, this was true of 64% of the patients. The short-term infusion was well tolerated, even in cases with unknown high pre-infusion serum levels. Pertinent pharmacokinetic parameters were determined, such as total body clearance, apparent volume of distribution, and half-life of elimination. Geometric mean and 95%-confidence limits, derived from the log-normal distribution of these parameters, were: Cl=0.044 (0.018–0.109) l/h/kg ideal body weight, Vd=0.451 (0.258–0.789) l/kg ideal body weight, and t1/2(el)=7.1 (2.6–19.1) h.
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    Components of variability in serum theophylline concentrations during maintenance therapy with a sustained release formulation (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 225-228 
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    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; sustained-release ; accumulation ; variability ; serum concentrations ; dosage prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen adult chronic asthmatic patients were studied on 6 consecutive days of the second week of treatment with a new sustained release theophylline formulation, and 8 were again studied after three months on the same dosing regimen (375 mg b.i.d.). Serum theophylline concentrations were maintained in the therapeutic range (peak −19.7±5.0 µg/ml; through −13.0±3.2 µg/ml) throughout the 12 hour dosing interval, and were greater than 75% of the peak concentration over 8.6±2.9 h. A degree of drug accumulation was evident in that the 1-h and 5-h levels rose from 12.2±4.1 and 14.5±4.8 µg/ml during the second week to 16.9±4.6 and 18.4±4.5 µg/ml, respectively, at three months. Between-patient differences accounted for 61%–71% of the total variation in steady state theophylline concentrations. After accounting for differences due to sampling time and assay error, unexplained random, within-individual variability amounted to 11%–18% of the total. Quantitative estimation of these components of variability may be incorporated into dosage forecasting methods based on single determinations of serum concentration.
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    Bioavailability and pharmacokinetics of theophylline following plain uncoated and sustained-release dosage forms in relation to smoking habit (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 361-369 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; smoking ; sustained release formulation ; dosage forms ; multidose pharmacokinetics ; bioavailability ; circadian variation in kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of theophylline following 10 days of multiple doses of a plain uncoated (640 mg, q.i.d.) and a sustained-release tablet formulation (600 mg, b.i.d.) were related to habitual smoking in 11 healthy adult male volunteers, who had previously taken part in a single-dose study of an intravenous preparation of theophylline and of the same oral dosage form. There were significant differences (p〈0.05 to 0.01) in the steady-state mean and minimum theophylline concentration and AUC between the groups (6 smokers versus 5 nonsmokers), but not between other variables. A difference (p〈0.05) in peak time was also found between the dosage forms. The mean elimination t1/2 was significantly (p〈0.05) shorter in smokers than in nonsmokers. The intersubject variability in plasma theophylline concentration observed on the final trial day in the smoking group was larger and diverged more from simulation curves generated from the mean pharmacokinetic parameters of the single-dose study of the same formulations as compared to that of the nonsmoking group. There was no significant difference between the two groups in the mean accumulation ratio and absolute bioavailability of the two dosage forms. The mean morning (7 a.m.) trough theophylline concentrations after both formulations were significantly (p〈0.05 to 0.01) greater than the evening (7 p.m.) values within the same group. The average number of reported side-effects was significantly (p〈0.001) greater during the earlier period (Days 1 to 3) than the later period of the trial. A trend was observed suggesting that the incidence of side-effects was less in smokers than in nonsmokers. The results indicate that smoking is a determinant not only of enhanced elimination of theophylline but that it also produces more variability in the plasma level, irrespective of the dosage form administered or the dosing scheme employed. There may be circadian variation in theophylline kinetics.
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    The effects of erythromycin on the absorption and disposition kinetics of theophylline (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 115-120 
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    ISSN: 1432-1041
    Keywords: asthma ; erythromycin ; theophylline ; absorption ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of erythromycin on the kinetics of theophylline were investigated in eight female patients with documented asthma in a crossover study. Theophylline pharmacokinetics were determined at steady state before and after one-week treatment with erythromycin stearate 250 mg given four times a day. Multiple serum samples were collected for 12 h after an aminophylline dose in the two drug treatment phases and assayed by high performance liquid chromatography. The resultant serum theophylline concentration-time data were analyzed by weighted, nonlinear regression analysis to obtain various pharmacokinetic parameters. In this study, the elimination half-live increased from 7.8±1.7 h on the control day to 9.5±1.4 h following treatment with the antibiotic (p〈0.02). The estimated apparent volume of distribution for theophylline (V/F) was also observed to increase from 0.42±0.09 l/kg before treatment with erythromycin to 0.53±0.15 l/kg after antibiotic treatment (0.05〈p〈0.10). In this study, no difference was demonstrated in the apparent clearance rate (Clapp), apparent first-order absorption rate constant (ka), maximum serum drug concentration (Cmax), time of maximum drug concentration (Tmax) or absorption lag time (tlag) for theophylline before and after treatment with erythromycin. With no apparent alteration in theophylline clearance following erythromycin coadministration, the decrease in the first-order elimination rate constant suggested that the apparent volume of distribution of theophylline is increased in the presence of erythromycin. It is concluded that patients maintained on theophylline derivatives should be closely monitored when erythromycin is coadministered.
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    Greatly enhanced bioavailability of theophylline on postprandial administration of a sustained release tablet (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 761-767 
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    ISSN: 1432-1041
    Keywords: theophylline ; bioavailability ; sustained release tablet ; pharmacokinetics ; Theograd-250
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of theophylline after oral administration of a new sustained release tablet Theograd®-250 mg was studied in 7 healthy volunteers, under fasting and non-fasting conditions. Whilst fasting the bioavailability was moderate at 64±22% (mean±SD), whereas in the non-fasting state the relatively high bioavailability of 90±13% was found. The drug appeared to be significantly more slowly absorbed when a tablet was taken after a meal, than when it was ingested on an empty stomach. In the former case, the peak level was reached after 6.9±1.0 h, whereas in the fasting state the maximum serum concentration occurred 4.0±1.7 h after administration of the drug. Despite the slow absorption, the peak non-fasting level of 4.4±1.4 mg·l−1 was significantly higher than the 3.1±1.0 mg·l−1 observed in the fasting state. The profiles of the serum concentration-time curves showed that the concentration remained above 75% of Cmax for 8.7±1.3 h in the fasting and 9.0±1.1 h in the non-fasting state. It was concluded that to define the optimal dosage regime for sustained release oral dosage forms of theophylline, the influence of food on absorption from these preparations should be taken into account. Based on the present results, Theograd®-250 mg tablets have predictable absorption and a high (90%) bioavailability if taken after a meal.
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    Non-linear elimination processes of theophylline (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 71-78 
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    ISSN: 1432-1041
    Keywords: nonlinear kinetics ; theophylline ; dimethyluric acid ; theophylline metabolism ; 1-methyluric acid ; 3-methylxanthine ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After intravenous and oral administration of theophylline to four healthy subjects, the plasma concentration-time curve of theophylline could be described by linear pharmacokinetics, although total clearance in all subjects decreased when the dose was increased; the doses were theophylline 193.2 mg and 386.4 mg i.v. and 161 mg and 322 mg p.o. Total clearance was 65.5±11.3 ml/min. Renal clearance changed from 15.2±9.5 ml/min in the first two hours after administration to 4.9±5.5 ml/min between 16 and 24 h (p〈0.001). 1,3-dimethyluric acid (DMU), the major metabolite of theophylline, was determined in urine and in plasma. The renal clearance of DMU was constant at 496.7±180 ml/min. There was some evidence that at high plasma concentrations of theophylline the formation of DMU might be a zero-order process. The renal excretion rate of 1-methyluric acid (1-MU) paralleled that of DMU, which is in accordance with the assumption that DMU is demethylated to 1-MU. 3-methylxanthine (3-MX) was excreted in urine at a constant rate over 10 h, the rate being equivalent to the dose, which is contrary to the assumption of Michaelis-Menten-kinetics. 3-methyluric acid was found to be a minor metabolite of theophylline and 1-methylxanthine (1-MX) could not be detected. The cumulative amounts excreted in urine, expressed as a percentage of the dose and corrected for molecular weight, were theophylline 16.6±6.5%, DMU 44.3±7.0%, 1-MU 24.3±4.8%, 3-MX 12.9±3.4% and 3-MU 2.2±1.8%.
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    Cardiovascular effects of two different xanthines in healthy subjects. Studies at rest, during exercise and in combination with a beta-agonist, terbutaline (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 319-324 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; enprofylline ; terbutaline ; haemodynamic response ; adenosine antagonism ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic response to two xanthines, enprofylline and theophylline, was studied in 6 healthy male volunteers at rest, during exercise and in combination with the beta2-agonist, terbutaline. At rest the haemodynamic effects of both xanthines were small and were qualitatively different from each other. While theophylline exerted a “pressor” response, enprofylline seemed to have arterial dilating ability. During exercise both xanthines as compared to placebo were associated with a higher heart rate and in general with increased systolic blood pressure. In combination with terbutaline enprofylline and theophylline both increased systolic blood pressure more than placebo, i. e. they augmented the positive inotropic effect of terbutaline. The systolic blood pressure was higher after theophylline than enprofylline despite their equipotent bronchodilator activity. This may reflect different inotropic effects of the xanthines as well as a difference in their influence on the response to adenosine.
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    A “once a day administration” sustained-release theophylline formulation: Disposition and pharmacokinetics (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 325-328 
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    ISSN: 1432-1041
    Keywords: theophylline ; sustained release ; pharmacokinetics ; chronic administration ; healthy volunteers ; plasma levels ; GCMS assay ; stable isotope technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new sustained-release preparation of theophylline (Dilatrane à Action Prolongée capsules filled with homogenous microgranules) has been after its studied administration to 7 healthy volunteers at 8 p.m. in order to achieve therapeutic levels at night and in the morning. In separate trials the test dose of 500 or 600 mg was administered for 7 days, once daily at 8 p.m. Plasma theophylline levels were measured by capillary gas chromatography with a mass specific detector after pentylation, using internal standards labelled with stable isotopes (15N-1,3 and 13C-2 theophylline). The new sustained-release preparation showed a monophasic regular absorption phase with very low interindividual variability. After administration, the plasma level stayed within 80% of the peak levels for 8.5±1.5 h. There was a good correlation between the dose and the steady state plasma level (r=0.9587; p〈0.05). This preparation can be chronically administered once daily day at 8 p.m. in order to achieve a therapeutic level during the night and the morning, and to provide sufficient protection during the nycterohemeral period, with a once dose a day schedule.
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    Attraction of bark beetles (Coleoptera: Scolytidae) to a pheromone trap (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 723-752 
    Details
    ISSN: 1573-1561
    Keywords: Ips typographus ; pheromone ; release ; recapture ; diffusion ; model ; Coleoptera ; Scolytidae ; trap ; marking ; dispersal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The movement of bark beetles near an attractive pheromone source is described in terms of mathematical models of the diffusion type. To test the models, two release experiments involving 47,000 marked spruce bark beetles [Ips typographus (L.)] were performed. The attractive source was a pheromone trap, surrounded by eight concentric rings with eight passive trap stations on each ring. Captures were recorded every 2–10 minutes for the pheromone trap and once for the passive traps. The models were fitted to the distribution in time of the central pheromone trap catch and to the spatial distribution of catch among the passive traps. The first model that gives a reasonable fit consists of two phases: Phase one—After release the beetles move according to a diffusion process with drift towards the pheromone trap. The strength of the drift is inversely proportional to the distance from the traps. Phase two—those beetles attracted to, but not caught by, the pheromone trap are no longer influenced by the pheromone, and their movement is described by a diffusion process without drift. In phase two we work with a loss of beetles, whereas the experiment seems to indicate that the loss of beetles in phase one is negligible. As a second model, the following modification of phase one is considered: After release the beetles move according to a diffusion process without drift, until they start responding to the pheromone (with constant probability per unit time), whereafter they start moving according to a diffusion process with drift. This study, like other release experiments, shows that the efficiency of the pheromone trap is rather low. What is specific for the present investigation is that we try to explain this low efficiency in terms of dynamic models for insect movement. Two factors seem to contribute: Some beetles do not respond to pheromone at all, and some beetles disappear again after having been close to the pheromone trap. It also seems that the motility of the beetles decreased after they ceased responding to the pheromone. Furthermore, the data lend some support to the hypothesis that flight exercise increases the response of the beetles to pheromone.
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    Receptor cells inIps typographus andDendroctonus micans specific to pheromones of the reciprocal genus (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 759-769 
    Details
    ISSN: 1573-1561
    Keywords: Ips typographus ; Dendroctonus micans ; Coleoptera ; Scolytidae ; exo-brevicomin ; (+)-ipsdienol ; single-cell recordings ; interspecific attraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Olfactory receptor cells were studied electrophysiologically inIps typographus andDendroctonus micans. The investigation revealed cells which were keyed to pheromone compounds characteristic of the reciprocal genus. Thus, cells keyed toexo-brevicomin were found inI. typographus, whereas cells keyed to (+)-ipsdienol were present inD. micans. Laboratory behavioral tests indicated an attractive effect of the two compounds on beetles of the reciprocal genus. InI. typographus the effect ofexo-brevicomin predominantly concerned males and enhanced their response to the pheromone “ipslure.” It is suggested thatexo-brevicomin serves as an interspecific attractant forI. typographus, which may be guided by pheromone compounds of the reciprocal genus in finding suitable breeding material. The function of (+)-ipsdienol inD. micans is more uncertain. It may be either a pheromone or an interspecific messenger.
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    Quantitative variation of pheromone components in the spruce bark beetleIps typographus from different attack phases (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 1029-1055 
    Details
    ISSN: 1573-1561
    Keywords: Ips typographus ; spruce bark beetle ; Coleoptera ; Scolytidae ; 2-methyl-3-buten-2-ol ; ipsenol ; cis-verbenol ; ipsdienol ; trans-verbenol ; verbenone ; myrtenol ; trans-myrtanol ; 2-phenylethanol ; ß-isophorone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Ips typographus beetles were collected in the field, separated into eight attack phases (from beetles walking on the trunk of a tree under attack to those excavating gallery systems with a mother gallery longer than 4 cm), and immediately frozen in liquid nitrogen. 2-Methyl-3-buten-2-ol,cis- andtrans-verbenol, verbenone, myrtenol, trans-myrtanol, ipsenol, ipsdienol, and 2-phenylethanol were quantified from excised hindguts against an internal standard, heptyl acetate, in the extraction solvent. Methylbutenol, the pinene alcohols, and 2-phenylethanol showed the same pattern of variation between attack phases in males, with the largest amounts present before accepting females and then a fast decline. Ipsenol and ipsdienol were not detected in males before the females were accepted, and the amounts increased when the females start their egg laying. Verbenone occurred only in trace amounts. The beetles were sampled from five Norway spruce trees (Picea abies) of differing resin flow. The correlations between the nine pheromone components and five major host monoterpenes in the gut showed that the variation in the amount of methyl-butenol, ipsenol, and ipsdienol could not be explained by the variation in the amounts of host monoterpenes. In contrast over 80% of the quantitative variation ofcis-verbenol,trans-verbenol, and myrtenol was explained by the amount of α-pinene. The nine pheromone components from 36 individual males were also quantified. Both methylbutenol andcis-verbenol showed a large variation in both amounts and proportions. Females containedtrans-verbenol and traces of most other components found in males. When accepted by the male, they also contained a female-specific compound, β-isophorone. Behavioral and biosynthetic implications of the results are discussed.
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    Multifunctionality of douglas-fir beetle pheromone 3,2-mch confirmed with solvent dibutyl phthalate (1980)
    Springer
    Journal of chemical ecology 6 (1980), S. 193-201 
    Details
    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; Dendroctonus pseudotsugae ; pheromone ; multifunctionality ; 3-methylcyclohex-2-en-l-one ; diluent ; dibutyl phthalate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Previous field and laboratory tests withDendroctonus pseudotsugae showing increased attractancy and chirp evocation by very low concentrations of the pheromone 3-methylcyclohex-2-en-1-one (3,2-MCH) dissolved in ethanol with known attractants were repeated with a different diluent, dibutyl phthalate (DBP). Other workers had speculated that the solvent ethanol was actually the synergist. Beetle response was essentially identical with both solvents, confirming the concentration-dependent multifunctionality of 3,2-MCH in Douglas-fir beetle behavior. Contradictions in available data with ethanol indicate unanswered questions about its effect withDendroctonus attractants.
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    Enantiomer-based specificity in pheromone communication by two sympatricGnathoirichus species (Coleoptera: Scolytidae) (1980)
    Springer
    Journal of chemical ecology 6 (1980), S. 445-456 
    Details
    ISSN: 1573-1561
    Keywords: Gnathotrichus retusus ; G. sulcatus ; Coleoptera ; Scolytidae ; ambrosia beetle ; aggregation pheromone ; 6-methyl-5-hepten-2-ol ; sulcatol ; reproductive isolation ; enantiomers ; chiral compounds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The aggregation pheromone ofGnathotrichus retusus was isolated and identified as (S)-(+)-sulcatol (6-methyl-5-hepten-2-ol). In laboratory and field experiments,G. retusus responded to (S)-(+)-sulcatol, but not to (±)-sulcatol, which was attractive to the sympatric species,G. sulcatus. G. sulcatus did not respond to optically pure (S)-(+)-sulcatol, but began to respond when ⩾ 1% (R)-(−)-sulcatol was present in an enantiomeric mixture.
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    Estimating western pine beetle-caused tree mortality for evaluating an attractive pheromone treatment (1980)
    Springer
    Journal of chemical ecology 6 (1980), S. 853-866 
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    ISSN: 1573-1561
    Keywords: Ponderosa pine mortality ; Dendroctonus brevicomis ; Coleoptera ; Scolytidae ; aerial photography ; detection ; estimation ; sampling ; mapping ; attractive pheromones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Sequential aerial photography was used to detect ponderosa pine trees killed by successive generations of the western pine beetle (WPB),Dendroctonus brevicomis Lec., over a three-year period during a study to evaluate the effectiveness of attractive pheromones for the suppression and survey of WPB. The total number of WPB-killed trees were estimated for each generation, using probability-proportional-to-size sampling procedures. Infested trees at the beginning of the suppression treatment totaled 283. Attacks by three successive WPB generations in 1970 killed 90,83, and 91 trees, respectively. The first generation in 1971 killed 47 trees and the two subsequent generations combined killed a total of 49 trees. During the suppression treatment, tree mortality was concentrated into the suppression plots in comparison to the check plots and the surrounding area. By 1972, tree mortality distribution returned to its original pattern, but at one-tenth the original level, as shown by maps. Recommendations suggest ways to improve the use of aerial photography for studies of WPB-caused tree mortality and population dynamics.
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    Electroantennogram responses ofScolytus multistriatus (Coleoptera: Scolytidae) to its pheromone components and to associated compounds (1982)
    Springer
    Journal of chemical ecology 8 (1982), S. 1333-1344 
    Details
    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; Scolytus multistriatus ; pheromone ; insect olfaction ; electroantennogram ; electrophysiology ; differential adaptation ; multistriatin ; 4-methyl-3-heptanol ; α-cubebene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Electroantennograms were recorded fromScolytus multistriatus in response to 4-methyl-3-heptanol, the four geometric isomers of multistriatin, and cubeb oil. Charateristic dose-response curves for response amplitude and the time required for the voltage trace to return to 1/2 baseline (recovery rate) were established. Recovery rates were significantly more rapid following stimulation with 4-methyl-3-heptanol or cubeb oil than with the multistriatin isomers. At most intensities, α-multistriatin, the isomer that evokes behavioral response, gave significantly larger EAGs with significantly longer recovery rates than the other isomers. Results of differential adaptation experiments suggested that 4-methyl-3-heptanol interacted with the processes involving multistriatin and cubeb oil activity. However, cross-activity of acceptors for these compounds seems unlikely; single sensillum recordings are needed to ascertain the response spectra for individual receptor neurons.
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    Frontalin in the male mountain pine beetle (1982)
    Springer
    Journal of chemical ecology 8 (1982), S. 1399-1409 
    Details
    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; Dendroctonus ponderosae ; pheromone ; frontalin ; exo-brevicomin ; Pinns contorta ; Pinus ponderosa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Frontalin andexo-brevicomin were identified by GC-MS in air drawn over maleDendroclonus ponderosae Hopk. (MPB) from Oregon that had joined females for 1–2 days in the bark of lodgepole and ponderosa pine logs. Unfed males releasedexo- andendo-brevicomin but not frontalin. These three compounds were not detected in either unfed or fed females. Arrestment of males bytrans-verbenol and terpenes in an olfactory walkway was reduced by the addition of racemic frontalin; production of attractant chirps also diminished. Racemic frontalin also strongly reduced the aggregation of MPB in lodgepole and ponderosa pine stands to sticky traps baited with the aggregation pheromonetrans-verbenol and host terpenes; however, the function of the natural enantiomer of frontalin in MPB is unknown.
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    Influence of opposite sex on attraction produced by pioneer sex of four bark beetle species cohabiting pine in the Southern United States (1982)
    Springer
    Journal of chemical ecology 8 (1982), S. 373-378 
    Details
    ISSN: 1573-1561
    Keywords: Dendroctonus frontalis ; Ips calligraphus ; I. grandicollis ; I. avulsus ; Coleoptera ; Scolytidae ; mating ; attraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Catches ofDendroctonus frontalis andIps avulsus on traps surrounding bolts infested with both sexes of each species in the gallery were not significantly different from catches at bolts infested only with the sex which normally pioneers the host colonization process. In contrast, the presence of the second sex in the gallery significantly reduced catches ofI. grandicollis andI. calligraphus and, additionally, the presence of females in the male galleries ofI. calligraphus significantly reduced the catch ofI. avulsus females as compared with their response to bolts infested with the maleI. calligraphus only.
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    Responses of the olfactory receptors ofScolytus scolytus (F.) (Coleoptera: Scolytidae) to the stereoisomers of 4-methyl-3-heptanol (1982)
    Springer
    Journal of chemical ecology 8 (1982), S. 477-492 
    Details
    ISSN: 1573-1561
    Keywords: Scolytus scolytus ; Coleoptera ; Scolytidae ; pheromone ; 4-methyl-3-heptanol stereoisomer ; olfaction ; electrophysiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Electroantennogram (EAG) and single-cell recording techniques have been used to demonstrate the presence of separate receptors for (−)-threo- and (−)-erythro-4-methyl-3-heptanol on the antenna ofS. scolytus. The majority of single-cell recordings showed spikes of two different amplitudes. The cell giving spikes of larger amplitude responded to the (−)-threo stereoisomer while the cell with the small-amplitude spikes responded to (−)-erythro-4-methyl-3-heptanol. It is suggested that in most recordings the two cells are associated with a single sensillum basiconicum.
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    1-Methylcyclohex-2-en-1-ol as an aggregation pheromone ofDendroctonus pseudotsugae (1983)
    Springer
    Journal of chemical ecology 9 (1983), S. 1533-1541 
    Details
    ISSN: 1573-1561
    Keywords: Aggregation pheromone ; attractant ; 1-methylcyclohex-2-en-1-ol ; Dendroctonus pseudotsugae ; Coleoptera ; Scolytidae ; bark beetle ; Douglas-fir beetle ; 3-methylcyclohex-3-en-1-ol ; Pseudotsuga menziesii
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract 1-Methylcyclohex-2-en-1-ol (1,2-MCH-ol) was synthesized, identified as a compound found in volatiles of the female Douglas-fir beetle, and shown by bioassays to be an aggregation pheromone. 1,2-MCH-ol matches in both GC retention index and mass spectrum a compound released by the female after feeding. 3,3-MCH-ol was also synthesized as a candidate compound; its mass spectrum is presented because published mass spectra are incorrect for this compound. Synthetic 1,2-MCH-ol increased arrestment and stridulation of males in olfactory walkways and increased trap catches of flying beetles. Males were more responsive to 1,2-MCH-ol than females.
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    Ethanol and other host-derived volatiles as attractants to beetles that bore into hardwoods (1983)
    Springer
    Journal of chemical ecology 9 (1983), S. 181-190 
    Details
    ISSN: 1573-1561
    Keywords: Coleoptera ; Buprestidae ; Cerambycidae ; Cleridae ; Scolytidae ; wood-boring beetles ; bark beetles ; ethanol ; host attractants ; hardwood tree insects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Ethanol, methanol, acetone, and acetaldehyde—chemicals identified in the inner bark of living trees—were used to bait vane traps placed in crowns of oak trees in Connecticut. Ethanol-baited traps caught more cerambycid, scolytid, and clerid beetles than unbaited traps. Buprestidae were not attracted to ethanol. Acetaldehyde and acetone were not attractive to any family. A mixture of ethanol, methanol, and acetaldehyde was no more attractive than ethanol alone. The vane traps were very effective at catching Cerambycidae and Scolytidae, but ineffective compared to sticky panels at catching Buprestidae.
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    Sensitivity of antennae of male and femaleIps paraconfusus (Coleoptera: Scolytidae) to their natural aggregation pheromone and its enantiomeric components (1983)
    Springer
    Journal of chemical ecology 9 (1983), S. 561-584 
    Details
    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; bark beetle ; Ips paraconfusus ; aggregation pheromone ; enantiomer ; electrophysiology ; electroantennogram ; interruption ; allomone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Antennae of male and femaleIps paraconfusus were equally and highly sensitive to their male-produced, multicomponent aggregation pheromone. Female and male antennae were highly sensitive to the pheromonal component, (S)-(−)-ipsenol, but essentially insensitive to its antipode, (R)-(+)-ipsenol. Further, female and male antennae were more sensitive to the pheromonal component, (S)-cis-verbenol, than to its antipode, (R)-cis-verbenol. Dramatic sexual dimorphism in chiral sensitivity to the ipsdienol enantiortiers was found, with female antennae being more sensitive to the conspecific pheromonal enantiomer, (S)-(+)-ipsdienol, and male antennae being more sensitive to the antipode, (R)-(−)-ipsdienol. Since (R)-(−)-ipsdienol is the principal pheromone of CaliforniaIps pini and interruptsI. paraconfusus aggregation, male antennae appear to be more sensitive to an interspecific allomone than a conspecific pheromone. Of the conspecific pheromonal enantiomers, both male and female antennae were most sensitive to (S)-(+)-ipsdienol, intermediately sensitive to (S)-(−)-ipsenol, and least sensitive to (S)-cis-verbenol. However, when enantiomeric sensitivities were compared to the estimated concentrations of these components in the natural pheromone, (S)-(~)-ipsenol tended to equal or approach the potency of (S)-(+)-ipsdienol as an antennal stimulant, while antennal responsiveness to (S)-cis-verbenol was dramatically less than for the other two pheromonal components. The behavioral implications of such physiological sensitivities are discussed in regard to perception of multicomponent synergistic pheromones and the relative efficacy of each component as an orientation cue.
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    Sensitivity of antennae of male and femaleIps paraconfusus (Coleoptera: Scolytidae) to its pheromone and other behavior-modifying chemicals (1983)
    Springer
    Journal of chemical ecology 9 (1983), S. 585-606 
    Details
    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; bark beetle ; Ips paraconfusus ; pheromone ; enantiomer ; electrophysiology ; electroantennogram ; interruption ; allomone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The antennal sensitivities of both male and femaleIps paraconfusus were found generally to be greatest for conspecific aggregation pheromones (ipsdienol, ipsenol); intermediate for an additional conspecific pheromone (cis-verbenol), an aggregation synergist (2-phenylethanol), and pheromones/allomones of sympatric species (trans-verbenol, verbenone, and frontalin); and lowest for both host terpenes (alpha-pinene and myrcene) and other bark beetle-produced odorants (exo-brevicomin and linalool). Of the enantiomeric compounds tested, antennae of both sexes did not differ in sensitivity between thetrans-verbenol enantiomers at low dosage levels; but at higher dosages, the conspecific-produced enantiomer, (1R,4S,5R)-(+)-trans-verbenol, elicited larger mean EAG responses than its antipode, (1S,4R, 5S)-(−)-trans-verbenol. At the mid-dosage range, female antennae tended to be slightly more responsive to (S)-(−)-verbenone than to (R)-(+)-verbenone, while male antennae were equally responsive to stimulations by either verbenone enantiomer. In field bioassays there was a large and significant reduction in trap catches ofI. paraconfusus on traps where the (S)-(−)- or (R)-(+)-enantiomers of verbenone were evaporated beside logs containing boring conspecific males. Only when the (S)-(−)-enantiomer of verbenone was evaporated beside logs containing boring males did the sex ratio ofI. paraconfusus trapped shift from female-dominated to male-dominated attraction. Thus both physiological and behavioral data suggest a differential chiral sensitivity of female beetles for the verbenone enantiomers. The relative sensitivities between different chiral compounds derived from one or the other of the common precursoral host terpenes, (S)-(−)- and (R)-(+)alpha-pinene or myrcene, are discussed.
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    Seasonal variation in laboratory response to behavioral chemicals of the southern pine beetle (1982)
    Springer
    Journal of chemical ecology 8 (1982), S. 641-652 
    Details
    ISSN: 1573-1561
    Keywords: Dendroctonus frontalis ; Coleoptera ; Scolytidae ; seasonal variation ; pheromone content ; environmental parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The response ofDendroctonus frontalis to an attractant mixture (frontalin,trans-verbenol, and loblolly pine turpentine) was measured in the laboratory over a four-year period. Beetle response was highest in late winter and early spring, and lowest in midsummer and early fall. Males consistently responded higher than females. Female beetles displayed significantly higher responses in early morning and late afternoon than in the middle of the day. Analysis of beetle pronotal width and fat content revealed a high degree of correlation between these two parameters in female beetles, but there was no correlation of response with either fat content or pronotal width for either sex. There was no evident relationship between mean monthly beetle response and total amounts of frontalin andtrans-veibenol found in hindgut extracts. Daily temperature in months both during which beetles were bioassayed and immediately prior to bioassay was highly correlated to response to the attractant.
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    Field bioassay ofexo- andendo-brevicomin withDendroctonus ponderosae in lodgepole pine (1982)
    Springer
    Journal of chemical ecology 8 (1982), S. 701-707 
    Details
    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; Dendroctonus ponderosae ; pheromone ; exo-brevicomin ; endo-brevicomin ; Pinus contorta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Bothexo- andendo-brevicomin reduced the response of flyingDendroctonus ponderosae (Coleoptera: Scolytidae) to an attractant composed oftrans-verbenol and terpenes or oftrans- andcis-verbenol and terpenes in a stand ofPinus contorta var.murrayana. These data suggest that racemicexo- andendo-brevicomin may interrupt aggregation in populations of mountain pine beetle colonizing lodgepole pine; functions of the natural chiral compounds are unknown.
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    Field response of the dutch elm disease vectors,Scolytus multistriatus (Marsham) andS. scolytus (F.) (Coleoptera: Scolytidae) to 4-methyl-3-heptanol baits containing α-, β-,δ-, or δ-multistriatin (1983)
    Springer
    Journal of chemical ecology 9 (1983), S. 67-84 
    Details
    ISSN: 1573-1561
    Keywords: Scolytus multistriatus ; S. scolytus ; Coleoptera ; Scolytidae ; elm bark beetle ; multistriatin stereoisomers ; Dutch elm disease ; aggregation pheromone ; field responses ; attractant baits
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The field responses of English populations of the Dutch elm disease vectors,Scolytus multistriatus andS. scolytus to baits containing 4-methyl-3-heptanol, a host synergist [(−)-α-cubebene or (−)-limonene] and (±)-α-, (+)-β-, (−)-β-, (±)-γ-, or (±)-δ-multistriatin were examined. (±)-α-Multistriatin, released at 5–10 μg/day, enhanced the response ofS. multistriatus to baits containing 4-methyl-3-heptanol and either of the host synergists but had no effect on the capture ofS. scolytus. The release of larger amounts (57 or 365 μg/day) of (±)-α-multistriatin interrupted the response of both species to the 4-methyl-3-heptanol baits. It appears that α-multistriatin has multiple functions as a behavior-modifying substance for the two beetles. The (+)-β-, (−)-β-, (±)-γ-, and (±)-δ-multistriatins were inactive when released at 5–10 μg/day. The results of these field experiments suggest that one bait can be formulated to capture both species.
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    Enhanced sensitivity to stimulation of sodium transport and cyclic AMP by antidiuretic hormone after Ca2+ depletion of isolated frog skin epithelium (1982)
    Springer
    The journal of membrane biology 69 (1982), S. 137-143 
    Details
    ISSN: 1432-1424
    Keywords: active sodium transport ; cyclic AMP ; frog skin epithelium ; antidiuretic hormone ; cell Ca2+ ; isoprenaline ; theophylline ; ADH receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The role of Ca2+ in the stimulation by antidiuretic hormone (ADH) of active sodium transport across the isolated epithelium of frog skin was investigated. This has been done by bathing the blood side with Ca2+-free solution containing 0.1mm EGTA. This Ca2+ depletion halved the resistance but had no significant effect on the short-circuit current (SCC). The sensitivity of both cAMP- and SCC-stimulation to ADH was increased 40-fold by Ca2+ depletion. Sensitivity to stimulation by theophylline was only changed a little, while stimulation by exogenous cAMP was completely unaltered. The increase in sensitivity to ADH was dependent on the duration of preincubation in Ca2+-free solution, which indicates that a slowly exchanging Ca2+ pool is involved in the determination of sensitivity to ADH. We suggest this pool is of cellular origin and the increased sensitivity is due to the decrease of a Ca2+ inhibition of the ADH-stimulated adenylate cyclase. But a direct effect of Ca2+ on binding of ADH to the receptor cannot be excluded. Our results are not compatible with the hypothesis that entry of extracellular Ca2+ is an obligatory step in the natriferic action of ADH, although it may be so in the hydroosmotic action of ADH. We also found the maximal response to ADH to be higher after Ca2+ depletion. This is in agreement with the hypothesis of intracellular Ca2+ as a modulator of the sodium permeability of the outward-facing membrane.
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    Intraindividual variability in theophylline pharmacokinetics: Statistical verification in 39 of 60 healthy young adults (1982)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 10 (1982), S. 123-134 
    Details
    ISSN: 1573-8744
    Keywords: theophylline ; pharmacokinetics ; variability ; disposition rate constant ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract After administering a single 300 mg dose of theophylline in oral solution to 12 healthy adults, the dose-normalized area under the plasma concentration-time curve was 97.2±20.1 % (mean±SD) of that after giving a 500 mg dose and statistically indistinguishable. Similarly, these areas multiplied by the individual's terminal disposition rate constant (β) were statistically indistinguishable between 300 and 500mg doses (99.1±10.3%), giving no evidence of dose-dependence for theophylline kinetics at the levels below 15 μg/ml observed in these individuals. After an intravenous dose, a shortlived distribution phase (t1/2α) is sometimes seen. An a phase, however, is hardly discernible in over 250 profiles arising from oral doses administered during five single dose bioavailability studies. Almost all such profiles appear to follow single-compartment model predictions. With precautions to avoid a potential a phase, a terminal log-linear slope can be fitted by least squares analysis with a relative standard error in the slope determination almost always less than 6%. Covariance analysis confirms statistically that 39 of the 60 participating individuals varied in their β on the different occasions each was required to take a dose during the course of a crossover bioavailability trial. In one study, even though each individual was observed on only two occasions, 9 out of 12 showed statistically identifiable variation in β. Fluctuations in β of 60% can be seen. Changes of 30% or greater are common and can occur within 3 or 4 days. Thus real, large, and potentially frequent changes in β of theophylline have been identified in a majority of normal subjects. These changes do not appear to be confined to either sex, to smokers or nonsmokers, or to heavier or lighter individuals. No chronological pattern has, as yet, been recognized in the intraindividual variability in β.
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    Evaluation of the absorption from some commercial enteric-release theophylline products (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 151-164 
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    ISSN: 1573-8744
    Keywords: theophylline ; absorption ; bioavailability ; enteric release ; tablets ; plasma concentrations ; dissolution data
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In a single-dose bioavailability study, Wales, Robinson, Columbia, and Choledyl (Warner/Chilcott) enteric-coated tablets all allowed a bioavailability of theophylline (99%±25%, 102%±23%,103%±18%, and 98%±15%;mean±SD, n=12) statistically indistinguishable from that of the standard uncoated tablet (Searle 200 mg aminophylline). Only the Wales and Choledyl tablets (7.6, 4.2 hr) could be shown (p〈0.05) to generate a peak plasma theophylline concentration later than the standard (1.4 hr). All tablet brands demonstrated a significant lag time before appearance of theophylline in the plasma, and both Wales and Choledyl tablets also had a (t peak -t tag )statistically different from that of the standard. Despite misleading indications from the mean plasma profile (plasma concentrations at each sampling time averaged over all subjects), plasma data from the individual participants and in vitrodissolution data show that, while release of theophylline from the Wales tablet might be inordinately slow, this is not a sustained-release preparation. Of the enteric-coated tablets only the Columbia product allowed significant levels in the first sample after dosage. Five of the 18 Columbia doses gave rise to 40–99%of the peak concentration in the 1- hr sample. In vitro,it takes 39±14 min for 40% of the theophylline content of Columbia tablets to dissolve in simulated intestinal fluid. Surprisingly rapid delivery of an entericcoated tablet to the duodenum would appear to be required to allow a significant percentage of theophylline to be dissolved and absorbed before 1 hr. None of 12 Columbia tablets tested in vitro,however, allowed dissolution of more than 0.2% of their theophylline content during 1 hr immersion in simulated gastric fluid. Since once in intestinal fluid Columbia tablets appear to dissolve more rapidly than the other enteric products, it is not clear whether the five Columbia tablets in question had imperfections or whether, in fact, this tablet brand more closely than the others represents the ideal of immediate release once in the duodenum. Plasma samples should be taken as early as 15 min after dosage when evaluating the bioavailability of enteric release products.
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    Evaluation of the absorption from 15 commercial theophylline products indicating deficiencies in currently applied bioavailability criteria (1980)
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    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 229-242 
    Details
    ISSN: 1573-8744
    Keywords: theophylline ; absorption ; tablets ; oral solution ; intravenous ; bioavailability criteria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The biovailability of theophylline from alcoholic and aqueous oral solutions was compared to that from an intravenous dose in 12 normal adults. The alcoholic elixir surprisingly gave rise to a significantly greater (114 ±14%, mean±sd amount absorbed than did the intravenous dose. The aqueous solution (99±8%) and intravenous dose were statistically indistinguishable in this respect, and, furthermore, the extent of absorption from a 300-mg dose of the aqueous solution was 99±10% of that from a 500-mg dose, and not statistically different. The aqueous solution was thus employed in three subsequent studies as a standard with which to compare 13 different types of theophylline tablets, all marketed in the United States. Of the 13 tablets, eight showed bioavailability statistically distinguishable from that of the standard. Nevertheless, for only two tablets could it be claimed with 95% confidence that the bioavailability was less than 95%. For none can it be stated at this confidence level that the bioavailability is less than 90%. Bioavailability studies should include criteria of clinical significance in addition to criteria of statistical significance. Contrary to the usual rationale behind choice of a bioavailability standard, nine of the 12 uncoated tablets appeared to allow more rapid absorption of theophylline than did the standard oral solution, an aqueous syrup. Increasing the dose of syrup decreased the rate of theophylline absorption. Orally administered drug solutions may have properties more absorption rate limiting than the disintegration of many brands of tablet.
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    Evaluation of the absorption from some commercial sustained-release theophylline products (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 131-149 
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    ISSN: 1573-8744
    Keywords: theophylline ; absorption ; bioavailability ; sustained release ; tablets ; plasma concentrations ; mean plasma concentrations ; steady-state projections
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Absorption of theophylline from three commercial products labeled as sustained release was compared to the absorption from a standard uncoated tablet (Searle 200-mg aminophylline tablet) in a single-dose study. Aminodur tablets (Cooper) and Slophyllin Gyrocap capsules (Dooner) had bioavailability (100.2%±19.8% and 98.5%±13.8%) statistically indistinguishable from that of the standard but showed significantly slower absorption (peak times of 10,4±2.8 and 4.36±1.35 hr) and lower peak plasma concentrations (13.9±4.5 and 22.6±3.5gmg/ml/g dose) than the standard (t peak ,1.52±0.45 hr; Cpeak,28.l±6.2μg/ml/g dose). The time of the plasma concentration peak (2.47±1.38 hr) after a dose of Tedral S.A. (Warner/Chilcott) was not statistically different from that after the standard, but both the peak concentration (16.0±3.9 gmg/ml/g dose) and bioavailability (76.0±18.4%) were. Multiple-dose projections from single-dose data indicate that of the three test products only Aminodur maintains reasonably constant interdose plasma levels during 12 hourly dosing. With an 8 hourly dosing schedule Gyrocaps also might be satisfactory. Reasonable predictions of the plasma concentrations arising from Aminodur doses have been made using a single-compartment body model and assuming input from an outer followed by an inner layer of the tablet. Typically a single dose of a preparation designed for constant release of drug over 12 hr should not produce a plasma concentration plateau in subjects with an average 6.1-hr drug half-life. The apparent plateau in the mean plasma profile (i.e., concentrations at each sampling time averaged over all subjects) for Aminodur doses is evaluated. The interpretation commonly being implied in the publication of mean profiles from bioavailability studies is misleading, particularly when applied to sustained-release preparations.
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    Zero-order rectal delivery of theophylline in man with an osmotic system (1982)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 10 (1982), S. 525-537 
    Details
    ISSN: 1573-8744
    Keywords: osmotic system ; zero-order drug delivery ; controlled release ; theophylline ; rectal administration ; steady-state ; in vivo/in vitro correlation ; saliva-plasma ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In vivoand in vitroperformances of a rectally applied osmotic delivery system containing a water-soluble derivative of theophylline were compared. The system was applied in six healthy volunteers during 72 h, and a comparison was made with two conventional dosage forms, a suppository and a solution administered orally, given once. In vitro,a perfect zero-order release rate with the osmotic system was obtained. In all subjects, application of the osmotic system resulted in a constant steady-state theophylline level just as in a long time zero-order i.v. infusion, which strongly suggests that the release rate in vivois zero-order too. The release rate was not influenced by renewing the dosage form after 36 hr or by defecation. The in vivoand in vitrorelease rates were almost identical and subjectindependent.
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    A method for estimating within-individual variability in clearance and in volume of distribution from standard bioavailability studies (1982)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 10 (1982), S. 135-146 
    Details
    ISSN: 1573-8744
    Keywords: theophylline ; intraindividual variability ; within-individual variability ; clearance ; volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Bioavailability studies are commonly undertaken, and most, because they involve subjects taking repeated doses of a drug, contain information on intraindividual variability in pharmacokinetics. However, because in such studies bioavailability itself is unknown, it is difficult to resolve which pharmacokinetic parameters vary within individuals. A mathematical model is presented which permits estimation of variability in clearance and in volume of distribution. When applied to pooled data arising from five theophylline bioavailability studies, this model has given statistical evidence that clearance of theophylline is inherently more variable within individuals (coefficient of variation, 13%) than volume of distribution (8%). As a result, use of the measurement AUC ·β rather than AUCas a more precise index of bioavailability is justified in studies where β is measured with reasonable precision. The model could be applied to estimation of withinbatch within-person variability in bioavailability.
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    Diffusion and flow transfer of theophylline across the blood-brain barrier: Pharmacokinetic analysis (1983)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 273-287 
    Details
    ISSN: 1573-8744
    Keywords: theophylline ; blood-brain barrie ; diffusion ; convolution ; model independent pharmacokinetics ; cerebrospinal fluid ; biopharmaceutics ; curve-fitting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Two possible schemes describing the transfer of theophylline across the blood-brain barrier are investigated. The first, the “diffusion only model,” assumes that the rate of transfer is proportional to the difference in free drug concentration in the serum and cerebrospinal fluid. The second, the “diffusion and flow model,” has the added feature that drug may be transferred from the CSF to the blood by the continuous secretion of CSF into the blood. Comparison of the results of nonlinear regression for the two proposed schemes indicated that the “diffusion and flow” model best describes the transfer process. The analysis indicates that the parameters obtained for the “diffusion and flow” model are physiologically meaningful.
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    URL: http://dx.doi.org/10.1007/BF01061868
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    Lack of influence of an intensive antacid regimen on theophylline bioavailability (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 315-331 
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    ISSN: 1573-8744
    Keywords: theophylline ; antacids ; interaction ; bioavailability ; steady state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We examined the influence of a large-volume, therapeutic antacid regimen, administered for three full days, on the steady-state bioavailability of a conventional-release and sustained-release theophylline product, Aminophyllin and Theodur, respectively. Nine stable asthmatics voluntarily completed a four-phase investigation requiring a total stay of 12 days in the Clinical Research Unit. The treatments consisted of administration of the formulations mentioned with and without antacids to each patient in a randomized sequence. Four patients participated in an additional phase where antacids were administered q2h around the clock for three days. After coadministration of theophylline plus antacids for two days, theophylline therapy was discontinued while numerous blood samples were obtained over 22 hr and analyzed for theophylline content via radioimmunoassay. Antacids had no predictable, consistent influence on theophylline absorption rate as determined by the absorption rate constant, the time to maximal theophylline concentration, or the lag time for theophylline absorption. Antacids had no detectable influence on theophylline elimination half-life and had no consistent, statistically significant effect on the extent of theophylline bioavailability, according to measurements of maximal concentration, AUCmeasured over the appropriate steady-state dosing interval, or elimination-rate adjusted AUC.The substantial intraindividual changes for all parameters of theophylline bioavailability that occurred for control and treatment phases likely represent spontaneous, random between-day variability in theophylline disposition independent of antacid administration, as evidenced by the comparability of the percent coefficient of variation for parameters of biovailability across all phases. Our data demonstrate that therapeutic antacid administration has no effect on steady-state theophylline bioavailability and does not alter the intrinsic variability in theophylline absorption. Based on the results of our data, it is unlikely that a clinically significant (〉20%) decrease in theophylline absorption would occur in any patient treated intensively with antacids concurrently.
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    URL: http://dx.doi.org/10.1007/BF01061723
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    A physiologically based pharmacokinetic model for theophylline disposition in the pregnant and nonpregnant rat (1984)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 12 (1984), S. 149-165 
    Details
    ISSN: 1573-8744
    Keywords: theophylline ; physiological model ; rat ; distribution ; tissues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract There are numerous studies which examine the disposition of theophylline from a traditional point of view. Information about the behaviour of drugs, including theophylline, is, however, very scarce when investigating the kinetics by means of a physiological flow model. This study is concerned with the development of a predictive analytical model for the pharmacokinetics of theophylline in nonpregnant and pregnant rats. This model postulates that specific organ or tissue masses may be simulated by compartments whose elements have physiological properties, e.g., tissue volumes, blood flow, and metabolic activity. A model has been developed that has blood, brain, hepatic, muscular, pulmonary, renal, and fetal tissues. With few exceptions, the agreement was good between predicted and calculated tissue data in the pregnant and nonpregnant rats. Finally, model simulations were performed to investigate the impact of different pulmonary extraction ratios on the concentration-time profile of theophylline in a “hypothetical” human patient.
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    Single cell responses of the Douglas-fir beetle,Dendroctonus pseudotsugae hopkins (Coleoptera: Scolytidae), to pheromones and host odors (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 583-600 
    Details
    ISSN: 1573-1561
    Keywords: Olfaction ; nerve cells ; bark beetle ; Dendroctonus pseudotsugae ; behavioral physiology ; Colcoptera ; Scolytidae ; neurobiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Olfactory perception of pheromones and host odors byDendroctonus pseudotsugae males and females was investigated through single cell recordings. Responses of 71 cells (35 cells in males; 36 cells in females) were recorded to 1 μg of 10 pheromones and three host terpenes. The olfactory cells were classified into four types based on sensitivity and specificity for the various odors: (1) 3,2-MCHone (3-methyl-2-cyclohexenone) cells; (2) 3,2-MCHol (3-methyl-2-cyclohexenol) cells; (3) frontalin cells; and (4) synergist cells. 3,2-MCHone and 3,2-MCHol cells in both males and females were the most sensitive and specific of all cells recorded with a threshold ca. 0.001–0.01 μg on filter paper. Frontalin cells were less specialized than the two aforementioned cell types and had a somewhat higher threshold of ca. 0.01 μg. A larger percentage of these three cell types were recorded in males than in females. The synergist cells had the highest threshold of all recorded cell types and were the least specific. Each of these cells was most responsive to eithercis-verbenol,trans-verbenol, 1,2-MCHol, verbenone, α-pinene, or limonene; however, responses could be elicited by stimulation with other pheromones or host terpenes at higher dosages. Instances of inhibition of nerve impulse activity from spontaneously active cells were observed during 3,2-MCHol and 3,2-MCHone stimulation, thus suggesting multifunctional effects for these compounds. The results help explain the role of chemicals in host selection, aggregation, and colonization behavior of the beetle and further elucidate hypotheses put forth in an earlier electroantennogram study.
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    Insect predator-prey coevolution via enantiomeric specificity in a kairomone-pheromone system (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 487-492 
    Details
    ISSN: 1573-1561
    Keywords: Dendroctonusfrontalis ; Coleoptera ; Scolytidae ; Thanasimus dubius ; Cleridae ; southern pine beetle ; kairomone ; behavior ; olfaction ; coevolution ; predator ; enantiomer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Insect predators can be guided to their prey by a kairomonal response to the prey pheromone. We found this phenomenon to be highly specific in the bark beetle predatorThanasimus dubius. Olfactory responses and behavioral tests revealed that the predator is guided to its major preyDendroctonusfrontalis by the primary enantiomer of the pheromone of the prey, (1S, 5R)-(−)-frontalin. These and other findings suggest the co-evolution of a kairomone system of the predator and the pheromone system of its prey.
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    Interconversion of verbenols and verbenone by identified yeasts isolated from the spruce bark beetleIps typographus (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 1349-1361 
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    ISSN: 1573-1561
    Keywords: Microbial transformations ; aggregation pheromones ; microorganisms ; yeasts ; bark beetle ; Coleoptera ; Scolytidae ; Ips typographus ; cis-verbenol ; trans-verbenol ; verbenone ; 3-methylbutanol ; 2-phenylethanol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Six yeast strains have been isolated and identified from the spruce bark beetle,Ips typographus. We have studied the ability of the yeasts to interconvertcis-verbenol,trans-verbenol, and verbenone. (1S)-cis-Verbenol is an active component in the aggregation pheromone ofIps typographus. The isolatedCandida molischiana/ Hansenula capsulata strain can convert both (1R)- and (1S)-cis-verbenol to verbenone. TheCandida nitratophila strain converts (1R)-cis-verbenol totrans-verbenol and (1S)-cis-verbenol to verbenone. Some of the yeast strains produce 3-methylbutanol, 2-methylpropanol, and 2-phenylethanol after growth in Sabouraud medium.
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    Response of the european elm bark beetle,Scolytus multistriatus, to host bacterial isolates (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 1133-1149 
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    ISSN: 1573-1561
    Keywords: Smaller European elm bark beetle ; Scolytus multistriatus ; Coleoptera ; Scolytidae ; elm bacterial isolates ; gamma irradiation ; trapping
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The response of the European elm bark beetle,Scolytus multistriatus, to host bacterial isolates was studied qualitatively under field conditions. Initial experiments indicated that such isolates were attractive to in-flight beetles. These isolates, identified asBacillus subtilis (five strains),B. pumilus, andEnterobacter cloacae, were grown on nutrient agar in glass vials and attached to sticky traps in elm woods. Although beetles were caught on the bacterial isolate-baited traps, the catches were variable, inconsistent, and often contradictory from one experiment to another. High numbers ofS. multistriatus were caught on traps baited with three strains ofB. subtilis, but in addition to thesubtilis strains, there were also aerial contaminants in the treatments, namelyE. aerogenes, Corynebacterium sp., andFlavobacterium sp. Also, relatively high catches were recorded on nutrient agar controls. When elm wood-bark plugs, sterilized (by gamma irradiation) and unsterilized, were placed in vials with the host bacterial isolates, the presence or absence of fresh elm, gamma irradiated or not, had no noticeable effect on beetle attractancy.
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    Attractive and inhibitory pheromones produced in the bark beetle,Dendroctonus brevicomis, during host colonization: Regulation of inter- and intraspecific competition (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 861-877 
    Details
    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; Cleridae ; Dendroctonus brevicomis ; Enoclerus lecontei ; Pinus ponderosa ; bark beetle ; exo-brevicomin ; frontalin ; verbenone ; trans-verbenol ; ipsdienol ; aggregation ; pheromone ; competition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Quantities of attractive (exo-brevicomin and frontalin) and inhibitory (trans-verbenol, verbenone, and ipsdienol) pheromones were monitored in both sexes ofDendroctonus brevicomis during their colonization of a ponderosa pine. Verbenone was found in males in the greatest amounts at the time of landing, and it declined more rapidly than the other pheromones in either sex. The amounts of frontalin andexo-brevicomin in males and females, respectively, increased after initial boring within the host but began to decline after mating. The quantity oftrans-verbenol in both sexes (females had significantly more) declined more gradually thanexo-brevicomin, frontalin, and verbenone. Ipsdienol was found only in males during the initial stages of attack when encountering the resin. It is suggested that along with a general decline in all pheromonal components, a sufficient change in the ratio of the attractive pheromones to an inhibitory pheromone,trans-verbenol, may play a role in termination of aggregation.trans-Verbenol may also function along with verbenone and ipsdienol in limiting the density of attack and thus intraspecific competition. These inhibitory pheromones also appear to cause several competing species of bark beetle to avoid landing in areas infested withD. brevicomis, even when their own pheromone is present.
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    Pheromonal attraction and allomonal interruption ofIps pini in California by the two enantiomers of ipsdienol (1980)
    Springer
    Journal of chemical ecology 6 (1980), S. 703-717 
    Details
    ISSN: 1573-1561
    Keywords: Scolytidae ; bark beetle ; Ips pini ; pheromone ; ipsdienol ; enantiomer ; interruption ; allomone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Air containing volatile compounds from around maleIps pini boring in ponderosa pine logs from California was condensed, fractionated by GC, and assayed in the laboratory and field. The only fraction that showed consistent activity in laboratory assays contained a single compound identified as ipsdienol (2-methyl-6-methylene-2,7-octadien-4-ol). Synthetic racemic ipsdienol showed no activity in either the laboratory or field. However, (−)-ipsdienol, the naturally occurring enantiomer, was attractive toI. pini in the laboratory and field, whereas (+)-ipsdienol interrupted the response ofI. pini to a natural source of attraction in field tests. (−)-Ipsdienol is a major component of the attractant pheromone of this species, since its level of activity in laboratory assays was quantitatively comparable to that of the condensed volatiles, and it was as attractive as maleI. pini boring in ponderosa pine in the field. (+)-Ipsdienol is a component of the pheromone of the competing species,I. paraconfusus.
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    Interspecific effects of pheromones on the attraction of the bark beetles,Dendroctonus brevicomis andIps paraconfusus in the laboratory (1981)
    Springer
    Journal of chemical ecology 7 (1981), S. 9-18 
    Details
    ISSN: 1573-1561
    Keywords: Dendroctonus brevicomis ; Ips paraconfusus ; Coleoptera ; Scolytidae ; Pinus ponderosa ; bark beetle ; exo-brevicomin ; frontalin ; myrcene ; verbenone ; ipsenol ; ipsdienol ; cis-verbenol ; attractants ; inhibition ; semiochemicals ; pheromones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Dendroctonus brevicomis was attracted to a mixture of theIps paraconfusus pheromones, ipsenol,cis-verbenol, and ipsdienol at 10−9 g each/μl but was not attracted to these pheromones at higher and lower release rates.I. paraconfusus was not attracted to theD. brevicomis pheromonesexo-brevicomin, frontalin, and myrcene at any release rate tested. Increased release rates of a mixture of the three pheromones ofI. paraconfusus inhibited the attraction ofD. brevicomis to its synthetic pheromones. A mixture of ipsenol + ipsdienol orcis-verbenol alone failed to cause inhibition indicating that at least two of theI. paraconfusus pheromones are required to inhibit the response ofD. brevicomis. The pheromones ofD. brevicomis did not inhibit the attraction ofI. paraconfusus to its pheromones; however, verbenone was a potent inhibitor.
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    Host selection behavior of bark beetles (Coleoptera: Scolytidae) attackingPinus ponderosa, with special emphasis on the western pine beetle,Dendroctonus brevicomis (1981)
    Springer
    Journal of chemical ecology 7 (1981), S. 49-83 
    Details
    ISSN: 1573-1561
    Keywords: Primary attraction ; tree predisposition ; Dendroctonus ; Ips ; Gnathotrichus ; Pityophthorus ; Coleoptera ; Scolytidae ; Buprestidae ; Verticicladiella ; Pinus ponderosa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Detection of weakened hosts from a distance by bark beetles through olfaction was investigated in field experiments. No significant numbers of Scolytidae were attracted to anaerobically treated pine bolts, stem disks, or sugar and ponderosa pine bark including phloem. Treatment of living trees with cacodylic acid induced attacks byDendroctonus brevicomis, D. ponderosae, Ips latidens, Gnathotrichus retusus, andPityophthorus scalptor, beginning two weeks after treatment. There was no significant difference between landing rates ofD. brevicomis andD. ponderosae on screened treated trees and screened controls. There was a significant increase in landing rates ofG. retusus andI. latidens, because both species had penetrated the screen and produced pheromones. Tree frilling alone did not increase the landing rate of bark beetles. Freezing of the lower trunk with dry ice did not increase significantly the landing rate ofD. brevicomis, D. ponderosae, G. retusus, orI. latidens on screened trees, whereas unscreened frozen trees were attacked by all four species. There was no significantly higher landing rate byD. brevicomis, D. ponderosae, I. paraconfusus, I. latidens, G. retusus, orHylurgops subcostulatus on screened trees evidencing symptoms of severe infection by the root pathogenVerticicladiella wagenerii, than on symptornless trees. These experiments show thatD. brevicomis, D. ponderosae, I. paraconfusus, I. latidens, andG. retusus land, apparently indiscriminately, on healthy and stressed hosts. Thus, in these species host discrimination must occur after landing and prior to sustained feeding.
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    An olfactometer for bark beetle parasites (1981)
    Springer
    Journal of chemical ecology 7 (1981), S. 359-366 
    Details
    ISSN: 1573-1561
    Keywords: Parasites ; bioassay ; Dendroctonus frontalis ; Coleoptera ; Scolytidae ; olfactometer ; bark beetles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract An “H”-type olfactometer was designed and built to test the response of bark beetle parasites to various beetle and tree host odors. The design has several advantages over other types of olfactometers. Strong air currents are not utilized, parasites have free movement in the test chamber, and a concentration gradient of test compound is maintained. Parasites tested in the olfactometer demonstrated strong positive responses to air drawn over logs infested with bark beetle larvae and varied responses to tree host odors.
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    Effect of mating on terminating aggregation during host colonization in the bark beetle,Ips paraconfusus (1981)
    Springer
    Journal of chemical ecology 7 (1981), S. 1135-1147 
    Details
    ISSN: 1573-1561
    Keywords: Ips paraconfusus ; Coleoptera ; Scolytidae ; Pinus ponderosa ; pheromone biosynthesis ; bark beetle ; myrcene ; α-pinene ; ipsenol ; ipsdienol ; cis-verbenol ; myrtenol ; attractants ; pheromones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Attraction of maleIps paraconfusus to male-infested ponderosa pine logs was inhibited by volatiles from logs infested with mated males and females over an 8-day period in the field. The response of females during this time was not significantly inhibited by these volatiles. Synthesis of the male-specific pheromones, ipsenol and ipsdienol, appeared negligible after 8 days in males allowed to mate with 3 females in these logs while males alone contained levels of these pheromones at about half their maximum rate. The decline in pheromone production in mated males appears to result, at least in part, from a reduction in the activity of the biosynthetic system that converts the host monoterpene, myrcene, to ipsenol and ipsdienol. Mating and feeding have apparently no effect on the biosynthetic system that converts the host monoterpene, (−)-α-pinene, to the pheromone,cis-verbenol in either males or females. The reduced production and release of pheromones by males after mating appears to play a major function in the process of terminating the aggregation phase of host colonization.
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    Response ofScolytus multistriatus (Coleoptera: Scolytidae) to α- and δ-multistriatin in Switzerland (1982)
    Springer
    Journal of chemical ecology 8 (1982), S. 1345-1352 
    Details
    ISSN: 1573-1561
    Keywords: Pheromone ; multistriatin ; 4-methyl-3-heptanol ; brevicomin ; frontalin ; Scolytus multistriatus ; Scolytus scolytus ; Scolytus pygmaeus ; Coleoptera ; Scolytidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Laboratory bioassays and field tests demonstrated that a Swiss population ofS. multistriatus responded much more strongly to α- than to δ-miltistriatin in combination with 4-methyl-3-heptanol and α-cubebene. High concentrations of brevicomin appeared to replace α-multistriatin in evoking a response byScolytus species, but this effect can be explained by the fact that the brevicomin was contiminated with small amounts of α-multistriatin. Frontalin, another bicyclic ketal, showed no biological activity. Field tests indicated thatS. pygmaeus aggregates to the same attractant mixture asS. multistriatus. S. scolytus also responded preferentially to this mixture, but the relative amounts of α-multistriatin to 4-methyl-3-heptanol do not appear to be as important as forS. multistriatus.
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    Influence of chemically mediated behavior on host tree colonization by four cohabiting species of bark beetles (1980)
    Springer
    Journal of chemical ecology 6 (1980), S. 395-414 
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    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; bark beetle ; Dendrocionus ; Ips ; pheromone ; colonization ; attraction ; inhibition ; behavioral interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Chemically mediated behavioral interactions among four species of Scolytidae cohabitingPinus taeda in east Texas appear to be significant in delineating breeding areas within trees and in influencing the sequence of colonization.Dendroctonus frontalis usually arrived first and was not attracted to logs occupied by any of the threeIps species (I. avulsus, I. calligraphus, andI. grandicollis). The response ofI. avulsus to conspecific males was enhanced by the simultaneous presence of actively boring maleI. grandicollis. The response ofIps calligraphus was inhibited in areas whereI. avulsus was also present, but, in turn,I. calligraphus inhibited the response ofI. grandicollis and attractedI. avulsus. Ips grandicollis was strongly inhibited by the simultaneous presence of femaleD. frontalis or maleI. calligraphus, and in turn, maleI. grandicollis inhibitedD. frontalis. The result of this highly interactive olfactory system is that host trees are colonized very rapidly and that, in the process, disadvantageous reproductive interactions are minimized.
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    Field responses of the western pine beetle1 and one of its predators to host- and beetle-produced compounds (1980)
    Springer
    Journal of chemical ecology 6 (1980), S. 625-641 
    Details
    ISSN: 1573-1561
    Keywords: Pinus ponderosa ; Dendroctonus brevicomis ; Temnochila chlorodia ; pheromone ; kairomone ; exo-bievicomm ; frontalin ; trans-ver-benol ; verbenone ; terpenes ; Coleoptera ; Scolytidae ; Trogositidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The responses of the western pine beetle (Dendroctonus brev-icomis LeConte) andTemnochila chlorodia (Mannerheim) to candidate attractants—exo- andendo-brevicomm, frontalin,trans-verbenol, ver-benone, and ponderosa pine turpentine and its major monoterpene components—were quantified by counts of beetles on traps baited with the various attractants, singly and in combinations released simultaneously. Combinations ofexo-brevicomin and frontalin plus a monoterpene or turpentine were the most attractive toD. brevicomis. The responses to these attractant combinations were reduced when verbenone plustrans-verbenol were present. All single compounds and binary mixtures, exceptexo-brevicomin plus frontalin, were much less attractive.exo-Brevicomin was most attractive toT. chlorodia, and this response appeared to decrease when verbenone plustrans-verbenol were present.
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    Possible allelopathic constituents ofCoffea arabica (1980)
    Springer
    Journal of chemical ecology 6 (1980), S. 643-654 
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    ISSN: 1573-1561
    Keywords: Coffea arabica ; allelopathy ; caffeine ; theobromine ; theophylline ; paraxanthine ; scopoletin ; chlorogenic acid ; vanillic acid ; p-hydroxybenzoic acid ; caffeic acid ; ferulic acid ; p-coumaric acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The aqueous extracts of leaves, stems, and roots ofCoffea arabica significantly inhibited the seed germination and radicle growth of rye grass, lettuce, and fescue. When the extracts were diluted to 1% solution, significant suppression of lettuce growth was still found and was particularly pronounced in the extract of young seedlings. The paper chromato-gram of the ether fraction of an aqueous extract of coffee leaves was bioassayed with lettuce seeds and revealed a remarkable inhibition throughout the chromatogram except for the segment ofR f 0.00–0.12. Paper without spotting extract was used as a standard. The phytotoxins present in coffee tissue were identified by paper and thin-layer chro-matography and mass spectrometry. The compounds include caffeine, theobromine, theophylline, paraxanthine, scopoletin, and chlorogenic, ferulic,p-coumaric,p-hydroxybenzoic, caffeic, and vanillic acids. All compounds except caffeic acid exhibited significant phytotoxicity to lettuce growth at a concentration of 100 ppm.
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    IPS pini: The basis for interpopulational differences in pheromone biology (1980)
    Springer
    Journal of chemical ecology 6 (1980), S. 677-687 
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    ISSN: 1573-1561
    Keywords: Ips pini ; Coleoptera ; Scolytidae ; aggregation pheromone ; ipsdienol ; interpopulational variation ; hybrid ; genetic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Ips pini from Idaho (ID) produce (−)-ipsdienol and respond to it in the laboratory.I. pini from New York (NY) produce (+) and (−)-ipsdienol in a 65∶35 ratio and respond much more strongly to the (+) than to the (−) enantiomer. Response byI. pini-ID to (−)-ipsdienol in the laboratory was inhibited by (+)-ipsdienol, while the field response byI. pini-NY was optimal to a 50:50 mixture of (+) and (−)-ipsdienol. This differential production and response to enantiomers of ipsdienol is sufficient to account for populational specificity observed in earlier experiments and confirmed by our current work. Reciprocal hybrids of the NY and IDI. pini populations did not differ in their patterns of attraction and response; those of both types of F1 were similar to NY beetles. Thus, it appears that (+)-ipsdienol is produced by the hybrids and is necessary for their maximum response, but this supposition was not tested. The genes controlling the pheromone biology ofI. pini are not sex linked. Since previous whole-antenna and single-cell electrophysiological data show that the receptor systems of the two populations are virtually identical, response behavior seems to be governed by the central nervous system rather than by the characteristics of the olfactory receptors.
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    URL: http://dx.doi.org/10.1007/BF00987678
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  • 88
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    Effects of verbenone andtrans-verbenol on the response ofDendroctonus brevicomis to natural and synthetic attractant in the field (1980)
    Springer
    Journal of chemical ecology 6 (1980), S. 997-1013 
    Details
    ISSN: 1573-1561
    Keywords: Pinus ponderosa ; Dendroctonus brevicomis ; verbenone ; trans-verbenol ; tree protection ; bark beetle ; pheromones ; interruptant ; Coleoptera ; Scolytidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Verbenone andtrans-verbenol were investigated as candidate interruptants for use as tree protectants. Verbenone andtrans-verbenol, pheromones released byDendroctonus brevicomis during host colonization, reduced the trap catch ofD. brevicomis near sources of the attractant composed ofexo-brevicomm, frontalin, and myrcene. Catch reduction at some trap positions was greater at a high release rate than at a low release rate oftrans-verbenol alone and of the combination of verbenone plustrans-verbenol. Verbenone also reduced catches at traps baited with attractive bolts from trees under attack byD. brevicomis. Attempts to use verbenone to protect living trees fromD. brevicomis attack were inconclusive.
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    URL: http://dx.doi.org/10.1007/BF00994657
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  • 89
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    Kairomone response inThanasimus predators to pheromone components ofIps typographus (1981)
    Springer
    Journal of chemical ecology 7 (1981), S. 305-312 
    Details
    ISSN: 1573-1561
    Keywords: Kairomone ; pheromone ; Thanasimus ; Ips typographus ; ipsdienol ; ipsenol ; cis-verbenol ; methylbutenol ; traps ; attractant ; behavior ; Scolytidae ; Cleridae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Thanasimus formicarius (L.) responds to racemic ipsdienol and ipsenol and less to (S)-cis-verbenol. All three are pheromone components in several bark beetles of the genusIps. Synergistic effects appeared when the components were combined. Methylbutenol alone, the specific pheromone component ofIps typographus, elicited no response, but synergestic effects appeared when methylbutenol was combined withcis-verbenol and ipsdienol. The sympatric speciesThanasimus femoralis (Zett.) responds to (S)-cis-verbenol, while ipsdienol and ipsenol synergize the response.
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    URL: http://dx.doi.org/10.1007/BF00995753
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  • 90
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    Evaluation of two attempts to trap defined populations ofScolytus multistriatus (1982)
    Springer
    Journal of chemical ecology 8 (1982), S. 125-136 
    Details
    ISSN: 1573-1561
    Keywords: Aggregation ; pheromone ; elm ; mark-release ; multilure ; Coleoptera ; Scolytidae ; Scolytus multistriatus ; trap-out ; Ulmus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Two experiments were conducted to investigate the use of a pheromone-based trap-out technique for suppressing populations ofScolytus multistriatus. In the first experiment, elm bolts containing the immature stages ofS. multistriatus were placed in an isolated community that contained elm trees, but which was essentially devoid of a resident beetle population. The infested bolts produced a total of 46,485 adult beetles of which 20% were recovered on traps baited with synthetic pheromone. In the second experiment beetles were released in a desert valley containing no resident elms or beetles. Only 1% of 20,000 released beetles were recaptured on traps erected on vertical cardboard cylinders and on elm logs. These rates of recapture are related to the attraction of beetles to naturally occurring brood sources versus pheromone-baited traps.
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    URL: http://dx.doi.org/10.1007/BF00984010
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  • 91
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    Male-specific conversion of the host plant compound, myrcene, to the pheromone, (+)-ipsdienol, in the bark beetle,Dendroctonus brevicomis (1982)
    Springer
    Journal of chemical ecology 8 (1982), S. 363-371 
    Details
    ISSN: 1573-1561
    Keywords: Dendroctonus brevicomis ; Coleoptera ; Scolytidae ; Pinus ponderosa ; pheromone biosynthesis ; bark beetle ; myrcene ; ipsdienol ; exo-brevicomin ; frontalin ; attractants ; pheromones ; competition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract When both sexes of the bark beetle,Dendroctonus brevicomis LeConte, were exposed to vapors of myrcene from ponderosa pine, only the male produced (+)-ipsdienol. In the field, racemic ipsdienol significantly reduced the attraction of both sexes in flight to a mixture of myrcene and the aggregation pheromones,exo-brevicomin and frontalin. This suggests that ipsdienol may be involved in regulating colonization density ofD. brevicomis. The implications of the biosynthesis of various enantiomers of ipsdienol byD. brevicomis and the cohabitating bark beetles,Ips paraconfusus andI. pini, in relation to their behavioral responses are discussed in regard to reducing interspecific competition.
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    URL: http://dx.doi.org/10.1007/BF00987784
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  • 92
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    Preference of certain scolytidae for different conifers (1982)
    Springer
    Journal of chemical ecology 8 (1982), S. 1093-1109 
    Details
    ISSN: 1573-1561
    Keywords: Scolytidae ; Coleoptera ; conifers ; terpenoids ; olfactory tests ; host attraction specificity ; statistical methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Nine Scolytidae (Cryphalus piceae, Cryphalus abietis, Pityokteines curvidens, Dendroctonus micans, Ips sexdentatus, Ips typographus,Orthotomicus erosus, Tomicus piniperda, andPhloeosinus bicolor) were subjected to olfaction tests on ten conifer species taken two by two. These conifers wereAbies cephalonica, Abies nordmanniana, Picea abies, Picea orientalis, Pinus pinaster, Pinus sylvestris, Pinus brutia, Pinus laricio,Cupressus atlantica, andCupressus sempervirens. A statistical study of the results, by means of the factorial analysis of correspondence completed by the duo preference test, commonly used in sensory analysis, revealed a taxonomic clustering by genus of the plant species and analogous specific attraction behavior for the insects.Pityokteines curvidens has a behavior analogous to that of the twoCryphalus considered.Phloesinus bicolor shows a very strong specificity forCupressus. The essential oils of the conifers were analyzed to determine their terpene composition and the ten odor spectra thus obtained were compared. The hierarchical classification, using a Euclidian distance, brought out similarities in the spectra, especially in the case ofPinus. It is shown that definitive establishment of Scolytidae is not due to the presence in the odor spectrum of any particular terpenoid. The attractive power of a species results from the synergism of the different terpenes. Moreover the definitive establishment of the insects also depends on their sensorial adaptation to volatile substances which can be wider or narrower for the species studied.
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    URL: http://dx.doi.org/10.1007/BF00986980
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  • 93
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    Sex-specific responses to aggregation pheromone Regulation of colonization density in the bark beetleIps paraconfusus (1983)
    Springer
    Journal of chemical ecology 9 (1983), S. 129-142 
    Details
    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; Ips paraconfusus ; bark beetle ; Pinus ponderosa ; ipsenoi ; ipsdienol ; cis-verbenol ; pheromone ; attractant ; intraspecific competition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract About equal numbers of each sex of flyingIps paraconfusus Lanier (Coleoptera: Scolytidae) were caught on traps several meters downwind from a male-infested ponderosa pine log releasing pheromone while a significantly different ratio of over four times more females than males were caught at the pheromone source. Females oriented directly to higher concentrations of colonizing males in a felled tree while males tended to land on the host in adjacent uncolonized areas. The attraction response of walking males to a 1∶1∶1 mixture of the synthetic pheromone components ispenol-ipsdienol-cis-verbenol was reduced progressively at higher concentrations while female response continued to increase. These responses may function to regulate density of colonization and limit intraspecific competition.
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    URL: http://dx.doi.org/10.1007/BF00987777
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  • 94
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    Antennal olfactory responsiveness of Douglas-fir beetle,Dendroctonus pseudotsugae Hopkins (Coleoptera: Scolytidae) to pheromones and host odors (1983)
    Springer
    Journal of chemical ecology 9 (1983), S. 1383-1395 
    Details
    ISSN: 1573-1561
    Keywords: Douglas-fir beetle ; Dendroctonus pseudotsugae ; Coleoptera ; Scolytidae ; electroantennograms ; host selection ; attractants ; aggregation ; 3-methylcyclohex-2-en-1-one ; 3-methylcyclohex-2-en-1-ol ; frontalin ; trans-verbenol ; verbenone ; limonene ; camphene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Electroantennograms were obtained fromD. pseudotsugae in response to the pheromones 3-methylcyclohex-2-en-1-one (3,2-MCHone), 3-methylcyclohex-2-en-1-ol (3,2-MCHol), frontalin,trans-verbenol, verbenone, and the host terpene hydrocarbons limonene and camphene. Male and female beetles were 10 and 100 times more sensitive to 3,2-MCH-one and 3,2-MCHol than to the other compounds. Of the other compounds, males were most sensitive totrans-verbenol, verbenone, and camphene, while females were most sensitive to frontalin, limonene, and camphene. The results parallel and help explain behavior of individual males and females during host tree selection, aggregation, and colonization.
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    URL: http://dx.doi.org/10.1007/BF00990745
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  • 95
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    Effects of multilure components on twig-crotch feeding by European elm bark beetles (1983)
    Springer
    Journal of chemical ecology 9 (1983), S. 1513-1523 
    Details
    ISSN: 1573-1561
    Keywords: Coleoptera ; Scolytidae ; Scolytus multistriatus ; European elm bark beetle ; pheromone ; epideictic pheromone ; twig-crotch feeding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The three components of the European elm bark beetle pheromone dispensed from polyethylene vials attached to the boles of healthy juvenile elms affected the rates of beetles landing and twig feeding on the baited trees. Maximum attraction to the tree occurred when all three pheromone components were presented together in a ratio of 1∶1∶8 for 4-methyl-3-heptanol (H), α-multistriatin (M), and α-cubebene (C). M released either alone or in excess of its natural ratio with H and C induced twig-crotch feeding. H presented alone had no effect on attraction or twig-crotch feeding, but in combination with M it induced landing on and boring into the tree bole. We concluded that the ratio of M and H being released influenced incoming beetles either to land on and colonize the bole or to feed in twig crotches. M in excess of H, known to occur when most females are mated, terminates colonization and deflects incoming beetles to crowns of elms.
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    URL: http://dx.doi.org/10.1007/BF00988417
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  • 96
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    TrappingDendroctonus brevicomis Changes in attractant release rate, dispersion of attractant, and silhouette (1983)
    Springer
    Journal of chemical ecology 9 (1983), S. 311-321 
    Details
    ISSN: 1573-1561
    Keywords: Dendroctonus brevicomis ; Temnochila chlorodia ; Coleoptera ; Scolytidae ; Trogositidae ; western pine beetle ; attractant ; pheromone ; trap ; behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract A sticky trap with 3 m2 surface area was modified by changes in attractant release rate, vertical dispersion of the attractant, and addition of a tree trunk silhouette to the trap axis. As attractant release rate increased, the number ofDendroctonus brevicomis caught at the source of attractant and at 1.5 and 5.2 m above ground on two vertical silhouettes 4.5 m away increased. In one experiment, more beetles were caught at a dispersed source of attractant than at a point source. Fewer beetles were caught at the lower traps on the two outlying silhouettes when a silhouette was at the source, than when no silhouette was at the source. As attractant release rate increased, the catch of a predator,Temnochila chlorodia, increased at the source.
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    URL: http://dx.doi.org/10.1007/BF00988451
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  • 97
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    Structure-activity correlations among analogs of 4-methyl-3-heptanol, a pheromone component of the european elm bark beetle (Scolytus multistriatus) (1983)
    Springer
    Journal of chemical ecology 9 (1983), S. 615-643 
    Details
    ISSN: 1573-1561
    Keywords: Structure-activity relationships ; pheromone ; Scolytus multistriatus ; Coleoptera ; Scolytidae ; Dutch elm disease ; electroantennogram ; chemoreception ; 4-methyl-3-heptanol ; analogs ; attractant ; aggregation ; beetle ; bark beetle ; alcohols ; ketones ; esters ; epoxides ; carboxylic acids ; amines ; isothiocyanates ; halides ; azides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract A number of analogs of the title compound (1), with several different functional groups in place of the 3-OH and with a variety of substituents, were tested for biological acitivity by a laboratory walking-beetle assay. The electroantennogram (EAG) response was determined for many of these, as well. Field tests with baited sticky traps were carried out on compounds with activity in the walking-beetle assay and/or that gave a high EAG response. Structure-activity correlations with parameters reflecting hydrophobic, steric, electronic, and van der Waals interactions with olfactory receptors were examined primarily on the basis of the behavioral tests. Electronic substituent effects on the 3-position functional group and steric effects were found to correlate best. It is suggested that the strength of a hydrogen bond to the 3-oxygen or 3-nitrogen (as proton acceptor) is important in chemoreception by receptors that are involved in the behavioral response.
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    URL: http://dx.doi.org/10.1007/BF00990413
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    Caffeine hazards and their prevention in germinating seeds of coffee (Coffea arabica L.) (1983)
    Springer
    Journal of chemical ecology 9 (1983), S. 1099-1106 
    Details
    ISSN: 1573-1561
    Keywords: Coffea arabica ; coffee ; caffeine ; theophylline ; germination inhibitors ; avoidance of autotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The inhibition of growth of seedlings of coffee (Coffea arabica L.) exposed to 10 m M caffeine was found to occur in the rootlet: mitosis and cell plate formation were also inhibited. Since concentrations of endogenous caffeine in the imbibed seed are 40–60 mM, 4–6 times as high as in the seedlings, we conclude that coffee embryos have specific means of avoiding caffeine autotoxicity. Observations indicate that cell divisions in root tips start only after the latter are pushed away from the caffeine-rich endosperm by elongation of the hypocotyl and maintained through cell elongation. Caffeine is introduced into the embryonic cotyledons mostly after cell division is completed there. Thus, coffee seedlings may avoid autotoxic effects of endogenous caffeine by separation between sites where mitosis is occurring and those where caffeine is stored. This is achieved in root tips by separation is space but in the cotyledons by separation in time. Caffeine is liberated from the tree litter in coffee plantations and eventually will produce autotoxic effects, resulting in some degeneration.
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    URL: http://dx.doi.org/10.1007/BF00982214
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  • 99
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    Southern pine beetle: Olfactory receptor and behavior discrimination of enantiomers of the attractant pheromone frontalin (1982)
    Springer
    Journal of chemical ecology 8 (1982), S. 873-881 
    Details
    ISSN: 1573-1561
    Keywords: Enantiomers ; bark beetle ; pheromone ; Dendroctonus frontalis ; Coleoptera ; Scolytidae ; southern pine beetle ; electrophysiology ; olfaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract In laboratory and field bioassays, the response ofDendroctonus frontalis was significantly greater to the mixture of (1S, 5R)-(−)-frontalin andalpha-pinene than to (1R,5S)-(+)-frontalin andalpfa-pinene. Electro-physiological studies revealed that antennal olfactory receptor cells were significantly more responsive to (1S, 5R)-(−)-frontalin than to (1R, 5S)-(+)-frontalin. Both enantiomers stimulated the same olfactory cells which suggests that each cell possesses at least two types of enantiomer-specific acceptors.
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    URL: http://dx.doi.org/10.1007/BF00994788
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  • 100
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    Response of the clerid predatorThanasimus dubius (F.) to bark beetle pheromones and tree volatiles in a wind tunnel (1984)
    Springer
    Journal of chemical ecology 10 (1984), S. 177-187 
    Details
    ISSN: 1573-1561
    Keywords: Coleoptera ; Cleridae ; Thanasimus dubius ; beetle ; predation ; frontalin ; ipsdienol ; α-pinene ; southern pine beetle ; Ips spp. ; Scolytidae ; ipsenol ; endo-brevicomin ; kairomone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Tree volatiles and pheromones produced by southern bark beetles were bioassayed for response by the clerid predatorThanasimus dubius (F.). Upwind flights in a laboratory olfactometer, modified from Visser (1976), were used to determine the attractiveness of compounds. Differences in response to a solvent control and pheromone treatment were tested for statistical significance using the Wilcoxon signed ranks test. Both sexes ofT. dubius responded to frontalin, ipsdienol, and α-pinene in a dose-dependent manner with different but overlapping concentration ranges. Strong differences between the sexes were observed in response totrans-verbenol, verbenone, andl-β-pinene. Neither sex responded to ipsenol orendo-brevicomin.
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    URL: http://dx.doi.org/10.1007/BF00987655
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