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  • 1
    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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  • 2
    Electronic Resource
    Electronic Resource
    Effect of oral slow-release terbutaline on early morning dyspnoea (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 159-162 
    Details
    ISSN: 1432-1041
    Keywords: terbutaline ; asthma ; slow-release formulation ; early morning dyspnoea ; side-effects ; serum terbutaline level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight male patients with partly reversible airflow obstruction, who had a diurnal variation in peak expiratory flow rate (PEFR) of more than 20% were treated with placebo and slow-release terbutaline tablets (5 mg at 08.00 hours and 10 mg at 20.00 hours) for 8 days. On Day 8 of each period, PEFR and serum terbutaline were measured at 4 and 2-h intervals, respectively. PEFR on the terbutaline day showed a significant increase at 08.00, 12.00, 24.00, 04.00 and 08.00 hours as compared to the placebo day. Slow-release terbutaline prevented early morning dyspnoea. The serum concentration was 3.3 ng/ml during the day and 3.5 ng/ml during the night. During terbutaline therapy the patients reported fewer complaints than during the placebo period. It was concluded that slow-release terbutaline tablets are suitable for twice daily treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609685
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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis and in patients with chronic renal disease (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 357-362 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; enprofylline ; liver cirrhosis ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis, patients with chronic renal failure, and healthy subjects, and have assessed the predictive value of routine tests of liver function and renal function (creatinine clearance) for theophylline and enprofylline total body clearances. Theophylline clearance was significantly decreased in the patients with liver cirrhosis compared with both the patients with renal failure and the healthy subjects (the mean values in the three groups were 24, 47, and 46 ml·h−1·kg−1 respectively. Enprofylline clearance was significantly decreased in the patients with chronic renal failure, compared with both the patients with liver cirrhosis and the healthy subjects (the values in the three groups were 64, 250, and 289 ml·h−1·kg−1 respectively. There was a strong correlation between creatinine clearance and enprofylline clearance, while there was only a poor correlation between the liver function tests and theophylline clearance. It appears that in various clinical situations enprofylline elimination can be predicted more precisely than theophylline elimination, which may make the drug safer in clinical practice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561364
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  • 5
    Electronic Resource
    Electronic Resource
    Creation of four consecutive instantaneous steady-state plasma concentration plateaus of theophylline and enprofylline by repeated infusions with exponentially decreasing delivery rates (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 657-661 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; enprofylline ; asthma ; pharmacokinetics ; intravenous infusion ; plateau levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Repeated exponentially decreasing influsions have been used to administer theophylline and enprofylline to show whether it would be feasible to create consecutive plasma concentration plateaus within a few hours. The infusions were carried out on two separate days in 8 stable asthmatics. Before the infusion experiments, the pharmacokinetics of the substances in the individual subjects were determined on a separate day. Plasma concentration rose to the desired level within 5 min after the start of the infusion at each dose level and a stable plasma concentration plateau was maintained during the following 90 min of the infusion. It was possible to achieve 4 subsequent concentration plateaus within a 6 h period. Use of this infusion method resulted in predictable plasma concentrations at all levels and so the method appears safe when the required plasma concentrations are below the toxic level. Apart from clinical situations where effective dosages of drugs must be administered rapidly, the method showed be useful in pharmacological dose-response studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637603
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ipratropium bromide after single dose inhalation and oral and intravenous administration (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 189-194 
    Details
    ISSN: 1432-1041
    Keywords: ipratropium bromide ; radioceptor assay ; pharmacokinetics ; inhalation ; systemic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single doses of ipratropium bromide were administered intravenously, orally and by slow inhalation to ten healthy male volunteers. The plasma level after oral administration followed a low but broad plateau persisting for several hours. After i.v. administration the kinetic parameters were: Vc=25.9 l, Vα=13.1 l, Vβ=338 l, $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\alpha }}} \right. \kern-\nulldelimiterspace} {2_\alpha }}} = 3.85\min $$ , $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\beta }}} \right. \kern-\nulldelimiterspace} {2_\beta }}} = 98.4\min $$ , AUC=15.0 h · ng/ml, kel=11.8 l/h and total clearance is 2325 ml/min. The bioavailability was 3.3% (range 0.9–6.1%) on comparing the plasma AUCs following i.v. and 20 mg oral administration. The cumulative renal excretion (0–24 h) after i.v. administration was compared with that after oral administration and inhalation. Following oral administration, the apparent systemic availability was around 2%, and after inhalation it was 6.9%. In comparison with oral placebo administration, only after i.v. administration was there a significant change in heart rate (from 63.7 to 90.2 beats/min). The systolic blood pressure rose from 115.1 to 119.6 mm Hg and the diastolic blood pressure from 68.3 to 78.3 mm Hg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609193
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  • 7
    Electronic Resource
    Electronic Resource
    Dutch approach to the study of the genetics of asthma (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 25 (1995), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1995.tb00418.x
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  • 8
    Electronic Resource
    Electronic Resource
    Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma (2002)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background There is a large variability in clinical response to corticosteroid treatment in patients with asthma. Several markers of inflammation like eosinophils and eosinophil cationic protein (ECP), as well as exhaled nitric oxide (NO), are good candidates to predict clinical response.Aim We wanted to determine whether we could actually predict a favourable response to inhaled corticosteroids in individual patients.Methods One hundred and twenty patients with unstable asthma were treated with either prednisolone 30 mg/day, fluticasone propionate 1000 µg/day b.i.d. or fluticasone propionate 250 µg/day b.i.d., both via Diskhaler. They were treated during 2 weeks, in a double-blind, parallel group, double dummy design. We measured eosinophils and ECP in blood and sputum, and exhaled nitric oxide as inflammatory parameters before and after 2 weeks in order to predict the changes in forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% fall in FEV1 (PC20 Mch), and asthma quality of life (QOL). Secondly, to test whether these results were applicable in clinical practice we determined the individual prediction of corticosteroid response.Results We found that changes in FEV1, PC20 Mch and QOL with corticosteroids were predominantly predicted by their respective baseline value and to a smaller extent by eosinophils in blood or sputum. ECP, measured in blood or sputum, was certainly not better than eosinophils in predicting clinical response to corticosteroids. Smoking status was an additional predictor for change in FEV1, but not for change in PC20 Mch or QOL. Prediction of a good clinical response was poor. For instance, high sputum eosinophils (≥ 3%) correctly predicted an improvement in PC20 Mch in only 65% of the patients.Conclusion Our findings show that baseline values of the clinical parameters used as outcome parameters are the major predictors of clinical response to corticosteroids. Eosinophil percentage in blood or sputum adds to this, whereas ECP provides no additional information. Correct prediction of clinical response in an individual patient, however, remains poor with our currently used clinical and inflammatory parameters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2002.01412.x
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  • 9
    Electronic Resource
    Electronic Resource
    Provocation with adenosine 5′-monophosphate, but not methacholine, induces sputum eosinophilia (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Introduction Bronchial hyper-responsiveness is usually measured with direct stimuli such as methacholine (MCh) or histamine. Adenosine 5′-monophosphate (AMP), which acts indirectly via the secondary release of mediators, is another stimulus to measure bronchial hyper-responsiveness.Aim To investigate whether provocation with inhaled AMP itself initiates an inflammatory response resulting in an influx of eosinophils into the airway lumen.Methods We have included 21 non-smoking atopic asthmatic subjects (mean FEV1 101% predicted, mean age 34 years). Each subject performed three sputum inductions on different days, at least seven days apart: one without previous provocation, one hour after PC20 methacholine, and one hour after PC20 AMP.Results After provocation with AMP, but not methacholine, the percentage of sputum eosinophils increased significantly (from 1.9±0.5% to 4.5±1% (P〈0.01) and 1.9±0.5% (P=0.89)). No changes in the percentages of neutrophils, lymphocytes, macrophages, or bronchial epithelial cells were found.Conclusion A provocation test with AMP leads to an increased percentage of sputum eosinophils. This observation cannot be explained by a non-specific response of the airways to a vigorous bronchoconstriction, since methacholine had no effect on inflammatory cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.01832.x
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  • 10
    Electronic Resource
    Electronic Resource
    Atopy and bronchial hyperresponsiveness: exclusion of linkage to markers on chromosomes 11q and 6p (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 22 (1992), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous studies have reported a familial predisposition for the development of atopy, bronchial hyperresponsiveness and clinical asthma, and therefore have suggested the presence of a heritable component to these disorders. The specific contributions of genetic and environmental factors in the pathogenesis of allergic disease and asthma have not been determined although Cookson et al. [1] have postulated linkage between atopy and chromosome 11q. We have studied 20 families (two and three generations) ascertained through a proband identified as having asthma (90% were also allergic) during the period of time between 1962 and 1970. Of those who were originally skin test positive, 82% remained positive. All probands whose pulmonary function allowed retesting (FEV1 〉 1.21) remained hyperresponsive to histamine. The children of these probands are now in the same age range as their parents when they were originally evaluated; 66% are atopic using criteria described by Cookson et al. (one or more positive skin tests ≥2 mm, an elevated total serum IgE or a positive specific IgE) and 22% demonstrate bronchial hyperresponsiveness (PC20 FEV1) to histamine. Using the highly polymorphic marker INT2 (which maps 2 cM from pλMS.51 on chromosome 11q) and atopy, we obtained a lod score of – 2.00 at a recombination fraction of 0.12. In addition, because many studies have suggested an association between atopy and certain HLA antigens, we investigated the possibility of linkage between atopy and bronchial hyperresponsiveness and D6S105, a polymorphic marker on chromosome 6p, located 7 cM from HLA-DR. For this marker and atopy, we observed a lod score of – 2.00 with a recombination fraction of 0.07. Similar results were observed with both of these markers and bronchial hyperresponsiveness. By restudying these probands as well as their family members, we were unable to find evidence for linkage between atopy or bronchial hyperresponsiveness and these regions of chromosomes 11 and 6 in this population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1992.tb00133.x
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