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1.
Using a double-blind, placebo-control, crossover study design, 8 asthmatic children (8-15 years) were evaluated for temporal patterns in airways function throughout separate study periods when treatment was placebo or Theo-24 once-daily on separate occasions at 0600, 1500 or 2100 hr. During 39-hr in-hospital observations, pulmonary function and serum theophylline concentrations (STC) were assessed every 3 hr under all treatments. The pharmacokinetics of Theo-24 varied greatly depending on the dosing time. For the afternoon and evening dosings, the Cmax, Tmax, AUC, % swing, % fluctuation, % AUC fluctuation, % nocturnal excess and Cav(2-6 hr) were all statistically significantly greater than for the morning dosing. Compared with the placebo regimen, dosing patients with Theo-24 at 1500 hr disrupted circadian patterns of airways function, especially airways patency, while dosing at 2100 hr, reduced the amplitude and shifted the acrophase of several spirometric measures to a slightly earlier time. Theo-24 treatment irrespective of dosing time resulted in comparable enhancement of the group 24-hr mean, minimum and maximum values of airways patency with reference to placebo baselines. Theo-24 dosing at 1500 or 2100 hr, however, resulted in the best effect on the airways as assessed by the 24-hr mean FEV 1.0 level in 7 of the 8 asthmatic children. When the drug was given at 1500 hr, the time of lowest FEV 1.0 was shifted from the nighttime hours in 5 of 8 patients. These findings suggest that clinicians need to individualize the theophylline dosing schedule of patients to best control the symptoms of asthma.  相似文献   

2.
Potential day-night differences of theophylline absorption and disposition were examined in day-active asthmatic children. Theophylline was given orally as TheoDur tablets and Somophyllin-CRT capsules (random crossover) every 12 hr (0700 and 1900), and patients were studied during two consecutive dosing intervals. In addition, patients were studied during the last 24 hr of a 48-hr continuous, intravenous aminophylline infusion. Serum theophylline concentrations were essentially constant during the intravenous infusion for the day and night periods. Thus, day and night clearances were nearly identical. Following oral administration of Somophyllin-CRT or TheoDur, areas under the serum concentration-time curves were greater during the day than the night, with Somophyllin-CRT yielding greater areas than TheoDur for both dosing intervals. Theophylline was absorbed more rapidly during the day than the night, as evidenced by a time to maximum concentration that occurred earlier in the daytime dosing interval. We conclude that theophylline clearance is not characterized by a circadian rhythm and that absorption of theophylline from Somophyllin-CRT and TheoDur is more rapid and complete during the day than the night.  相似文献   

3.
As many as 80 percent of asthmatics experience nighttime or early-morning episodes, which are difficult to treat and potentially fatal. The greater-than-normal amplitude of circadian airflow variation in many asthmatics contributes heavily to the genesis of the early ‘morning dip’. Beta-agonists and corticosteroids are of limited usefulness in nocturnal asthma, and slow-release theophylline drugs, while potentially effective, vary in 24-hr blood profile and hence their influence on nocturnal episodes. Traditional 12-hr ‘symmetric’ theophylline regimens, instead of meeting increased nocturnal demands, may actually produce lower night- than daytime blood levels. On the other hand, appropriately timed administration of a once-daily theophylline drug might provide maximum blood levels when needed and help stabilize 24-hr airflow.

Accumulated data, summarized in this review, demonstrate the chronotherapeutic potential of single-daily evening doses of a controlled-release theophylline preparation (Uniphyl® 400-mg tablets*) in nocturnal and early morning asthma. Nighttime blood concentrations with this regimen were higher than were those with Theo-Dur® tablets, ? B.I.D., in the same total daily doses, or with once-daily morning Uniphyl administration. In fed and fasted subjects, evening administration of Uniphyl 400-mg tablets was well tolerated and did not lead to ‘dose dumping.’ Clinically, this treatment demonstrated advantages over B.I.D. theophylline, over single-daily morning regimens, and over prior theophylline therapy. Advantages of the evening regimen included better early-morning airflow (without significant decline later in the day), more effective symptom control, better patient acceptance, fewer night awakenings, and the obvious convenience of once-daily dosing. In addition, lung function showed greater stability, throughout the day, with once-daily evening therapy than with traditional 12 hr dosing.

Uniphyl 400-mg tablets may be administered once daily to provide maximum blood levels at the time of peak bronchoconstriction, whether at night or during the day.  相似文献   

4.
As many as 80 percent of asthmatics experience nighttime or early-morning episodes, which are difficult to treat and potentially fatal. The greater-than-normal amplitude of circadian airflow variation in many asthmatics contributes heavily to the genesis of the early 'morning dip'. Beta-agonists and corticosteroids are of limited usefulness in nocturnal asthma, and slow-release theophylline drugs, while potentially effective, vary in 24-hr blood profile and hence their influence on nocturnal episodes. Traditional 12-hr 'symmetric' theophylline regimens, instead of meeting increased nocturnal demands, may actually produce lower night- than daytime blood levels. On the other hand, appropriately timed administration of a once-daily theophylline drug might provide maximum blood levels when needed and help stabilize 24-hr airflow. Accumulated data, summarized in this review, demonstrate the chronotherapeutic potential of single-daily evening doses of a controlled-release theophylline preparation (Uniphyl 400-mg tablets) in nocturnal and early morning asthma. Nighttime blood concentrations with this regimen were higher than were those with Theo-Dur tablets, B.I.D., in the same total daily doses, or with once-daily morning Uniphyl administration. In fed and fasted subjects, evening administration of Uniphyl 400-mg tablets was well tolerated and did not lead to 'dose dumping.' Clinically, this treatment demonstrated advantages over B.I.D. theophylline, over single-daily morning regimens, and over prior theophylline therapy. Advantages of the evening regimen included better early-morning airflow (without significant decline later in the day), more effective symptom control, better patient acceptance, fewer night awakenings, and the obvious convenience of once-daily dosing. In addition, lung function showed greater stability, throughout the day, with once-daily evening therapy than with traditional 12 hr dosing. Uniphyl 400-mg tablets may be administered once daily to provide maximum blood levels at the time of peak bronchoconstriction, whether at night or during the day.  相似文献   

5.
With the introduction of sustained-release theophylline formulations for once-daily dosing or for unequally divided twice-daily dosing, comparison with conventional equally divided twice-daily dosing has been focused on nocturnal serum theophylline concentrations (STCs), plateau properties and peak-trough fluctuation. The merits of various steady-state characteristics such as nocturnal excess, plateau time, residual concentration, peak-trough fluctuation, swing and AUC fluctuation are illustrated by 15 data sets from 7 multiple-dose studies, each including either 10-12 healthy volunteers or 12-20 COPD-patients. In all of the studies, STCs were determined at least every 2 hr over a 24-hr period in steady-state. Included in the studies were 7 sustained-release theophylline formulations which were administered either once daily (in the morning or in the evening), or twice daily (either equally divided, or unequally divided with one-third of the dose being given in the morning and two-thirds in the evening.  相似文献   

6.
With the introduction of sustained-release theophyllíne formulations for once-daily dosing or for unequally divided twice-daily dosing, comparison with conventional equally divided twice-daily dosing has been focused on nocturnal serum theophylline concentrations (STCs), plateau properties and peak-trough fluctuation. The merits of various steady-state characteristics such as nocturnal excess, plateau time, residual concentration, peak-trough fluctuation, swing and AUC fluctuation are illustrated by 15 data sets from 7 multiple-dose studies, each including either 10–12 healthy volunteers or 12–20 COPD-patients. In all of the studies, STCs were determined at least every 2 hr over a 24-hr period in steady-state. Included in the studies were 7 sustained-release theophylline formulations which were administered either once daily (in the morning or in the evening), or twice daily (either equally divided, or unequally divided with one-third of the dose being given in the morning and two-thirds in the evening).  相似文献   

7.
We investigated changes in the circadian rhythm of peak expiratory flow (PEF) in seven persons with nocturnal asthma for a 24h span when (1) they were symptom free and their disease was stable, (2) their asthma deteriorated and nocturnal symptoms were frequent, and (3) they were treated with theophylline chronotherapy. Subjects recorded their PEF every 4h between 07:00 and 23:00 one day each period. Circadian rhythms in PEF were assessed using the group-mean cosinor method. The circadian rhythm in PEF varied according to asthma severity. Significant circadian rhythms in PEF were detected during the period when asthma was stable and when it was unstable and nocturnal symptoms were frequent. When nocturnal symptoms were present, the bathyphase (trough time) of the PEF rhythm narrowed to around 04:00; during this time of unstable asthma, the amplitude of the PEF pattern increased 3.9-fold compared to the symptom-free period. No significant group circadian rhythm was detected during theophylline chronotherapy. Evening theophylline chronotherapy proved to be prophylactic for persons whose symptoms before treatment had occurred between midnight and early morning. Changes in the characteristics of the circadian rhythm of PEF, particularly amplitude and time of bathyphase, proved useful in determining when to institute theophylline chronotherapy to avert nocturnal asthma symptoms. (Chronobiology International, 17(4), 513–519, 2000)  相似文献   

8.
Three regimens of sustained-release theophylline (SRT), Theostat were administered to 12 male patients with chronic obstructive pulmonary disease in a randomized cross-over trial. Each 7-day treatment consisted of: treatment A--8 mg/kg at 0700 hr and 4 mg/kg at 1900 hr, treatment B--6 mg/kg at 0700 hr and 6 mg/kg at 1900 hr, treatment C--4 mg/kg at 0700 hr and 8 mg/kg at 1900 hr. Peak expiratory flow (PEF) was recorded each day at 0700, 1100, 1500, 1900 and 2300 hr and theophylline plasma levels were determined on the 7th day of each treatment sequence. Cosinor analysis of the data revealed significant circadian rhythms in PEF for each treatment: the mesor (24-hr average) was significantly higher with C and acrophases (phi, peak time of PEF rhythm) were located at 1426 hr for A and 1425 hr for C; a shift of the acrophase to an earlier timing was detected for B (phi = 0958 hr. These findings suggest that an unequal, twice-daily SRT dosing with the greater amount of drug at night may be beneficial in the treatment of COPD.  相似文献   

9.
The effect of different times of evening administration (2000 hr versus 2200 hr) of sustained-release aminophylline (Euphyllin®CR) on pharmacokinetics and lung function was investigated in 30 patients presenting with moderately severe asthma. The study protocol followed a randomized three-period change-over design including a placebo period. As the dosing of the investigated SR-formulation is circadian rhythm adapted, the major part of the daily dose, namely 2/3, is affected by the change in time of administration. With regard to the nocturnal peak expiratory flow (PEF), no statistically significant difference between the times of evening administration was detected. However, the concomitant requirement for corticosteroids and inhaled beta-2-mimerics complicates the assessment of the relative clinical efficacy of the major dosing of theophylline during the 24 hr even though this drug is usually not given as a monotherapy in severe patients with reversible airway obstruction.  相似文献   

10.
This was an open-label study in 19 children aged 9-13 years, weighing 27-44 kg, with bronchial asthma. Twenty-four-hour steady-state concentrations of theophylline and its metabolites 1,3-dimethyl uric acid, 3-methyl xanthine and 1-methyl uric acid were assessed after daily dosing of 600 mg (ca 18 mg/kg/day) of the sustained-release theophylline micro-pellet sprinkle system BY158K, for 4 days. The dosing regimen used was an unequal twice-daily dose of 200 mg in the morning after breakfast and 400 mg in the evening after dinner. Twenty-four-hour peak expiratory flow (PEF) profiles were compared before treatment and at steady-state, along with lung function parameters after bronchial provocation. Mean values +/- SD (n = 16) of the steady-state characteristics were Cmin 6.8 +/- 2.1 mg/l, Cmax 14.5 +/- 4.8 mg/l and Cav 10.5 +/- 2.9 mg/l, the plateau time was 11.7 +/- 4.8 hr and peak-trough fluctuation and swing were 72 +/- 21 and 118 +/- 52%, respectively. There was an excellent reproducibility of theophylline pre-dose levels at corresponding time points of the 24-hr sampling period [r = 0.864 (p less than 0.001)]. Mean values +/- SD of the 24 hr average serum metabolite levels were 0.9 +/- 0.2 mg/1 for 1,3-dimethyl uric acid, 0.6 +/- 0.1 mg/1 for 3-methyl xanthine and 0.4 +/- 0.1 mg/1 for l-methyl uric acid. Lung function (n = 17) following bronchial provocation, improved in 10 children after theophylline treatment of 4 days, remained stable in 2 patients and deteriorated in 5 patients. Serum theophylline profiles and PEF profiles ran largely in parallel over the 24-hr period. Six children exhibited typical theophylline induced side-effects, headache (n = 3), nausea (n = 4), dizziness (n = 1), vomiting (n = 4), sleep disturbances (n = 1), pallor (n = 1) and tremor (n = 1), necessitating in 3 children one dose omission/reduction (n = 2) or subsequent dose reduction (n = 1). It has been shown that a twice daily dosing regimen with unequal doses of anhydrous theophylline (BY158K) is well suited to this population of fast metabolisers. The patients were well protected throughout the day, including the critical early morning hours.  相似文献   

11.
Three regimens of sustained-release theophylline (SRT), Theostat® were administered to 12 male patients with chronic obstructive pulmonary disease in a randomized cross-over trial. Each 7-day treatment consisted of

treatment A—8 mg/kg at 0700 hr and 4 mg/kg at 1900 hr

treatment B—6 mg/kg at 0700 hr and 6 mg/kg at 1900 hr

treatment C—4 mg/kg at 0700 hr and 8 mg/kg at 1900 hr.

Peak expiratory flow (PEF) was recorded each day at 0700, 1100, 1500, 1900 and 2300 hr and theophylline plasma levels were determined on the 7th day of each treatment sequence. Cosinor analysis of the data revealed significant circadian rhythms in PEF for each treatment: the mesor (24-hr average) was significantly higher with C and acrophases (Φ, peak time of PEF rhythm) were located at 1426 hr for A and 1425 hr for C; a shift of the acrophase to an earlier timing was detected for B (Φ = 0958 hr. These findings suggest that an unequal, twice-daily SRT dosing with the greater amount of drug at night may be beneficial in the treatment of COPD.  相似文献   

12.
The effect of different times of evening administration (2000 hr versus 2200 hr) of sustained-release aminophylline (Euphyllin CR) on pharmacokinetics and lung functions was investigated in 30 patients presenting with moderately severe asthma. The study protocol followed a randomized three-period change-over design including a placebo period. As the dosing of the investigated SR-formulation is circadian rhythm adapted, the major part of the daily dose, namely 2/3, is affected by the change in time of administration. With regard to the nocturnal peak expiratory flow (PEF), no statistically significant difference between the times of evening administration was detected. However, the concomitant requirement for corticosteroids and inhaled beta-2-mimetics complicates the assessment of the relative clinical efficacy of the major dosing of theophylline during the 24 hr even though this drug is usually not given as a monotherapy in severe patients with reversible airway obstruction.  相似文献   

13.
We investigated changes in the circadian rhythm of peak expiratory flow (PEF) in seven persons with nocturnal asthma for a 24h span when (1) they were symptom free and their disease was stable, (2) their asthma deteriorated and nocturnal symptoms were frequent, and (3) they were treated with theophylline chronotherapy. Subjects recorded their PEF every 4h between 07:00 and 23:00 one day each period. Circadian rhythms in PEF were assessed using the group-mean cosinor method. The circadian rhythm in PEF varied according to asthma severity. Significant circadian rhythms in PEF were detected during the period when asthma was stable and when it was unstable and nocturnal symptoms were frequent. When nocturnal symptoms were present, the bathyphase (trough time) of the PEF rhythm narrowed to around 04:00; during this time of unstable asthma, the amplitude of the PEF pattern increased 3.9-fold compared to the symptom-free period. No significant group circadian rhythm was detected during theophylline chronotherapy. Evening theophylline chronotherapy proved to be prophylactic for persons whose symptoms before treatment had occurred between midnight and early morning. Changes in the characteristics of the circadian rhythm of PEF, particularly amplitude and time of bathyphase, proved useful in determining when to institute theophylline chronotherapy to avert nocturnal asthma symptoms. (Chronobiology International, 17(4), 513-519, 2000)  相似文献   

14.
目的:研究肺通气功能程度与慢性阻塞性肺疾病患者夜间低氧发生的相关性。方法:选取2012年1月至2013年6月我院治疗的60例稳定期慢性阻塞性肺疾病患者,按肺通气功能分为轻度、中度、重度、极重度4组,每组15例,监测记录研究对象肺通气功能指标及夜间血氧指标,比较各组监测指标的差异,并分析其相关性。结果:不同病情程度COPD患者FEV1/FVC、FEV1、FVC、PEF、RV、RV/TLC、MsaO2、ODI、WsaO2、LsaO2、SIT90%有差异(P0.05);极重度和重度比较FEV1/FVC、FEV1、RV、MsaO2、ODI、WsaO2、LsaO2、SIT90%有差异(P0.05);极重度和中度比较FEV1/FVC、FEV1、FVC、PEF、RV、RV/TLC、MsaO2、ODI、WsaO2、LsaO2、SIT90%有差异(P0.05);极重度和轻度比较FEV1/FVC、FEV1、FVC、PEF、RV、RV/TLC、MsaO2、ODI、WsaO2、LsaO2、SIT90%有差异(P0.05);重度和中度比较FEV1/FVC、FEV1、FVC、PEF、RV/TLC、MsaO2有差异(P0.05);重度和轻度比较FEV1/FVC、FEV1、FVC、PEF、RV/TLC、MsaO2、ODI、LsaO2有差异(P0.05);中度和轻度比较FEV1/FVC、FEV1、FVC、PEF、ODI有差异(P0.05)。COPD患者的肺通气功能FEV1与MsaO2呈正相关(r=0.683,P0.05)。结论:肺通气功能程度与慢性阻塞性肺疾病患者夜间低氧发生具有相关性。  相似文献   

15.
In two double-blind, multiple-dose cross-over studies the therapeutic effects of SR theophylline preparations given once each night (mean 11.2 mg/kg per day) versus twice daily in equal doses (mean 10.3 mg/kg per day) (study I) and SR-terbutaline in equal doses (mean 0.25 mg/kg per day) versus SR theophylline in unequally divided daily doses (mean 5.3 mg/kg morning dose, 10.6 mg/kg evening dose) study II) were compared in 19 patients with nocturnal asthma. At the end of each treatment period drug serum concentrations and PEFR were measured every 2 hr over a 24-hr period. With the twice-daily, equally divided regimen, serum theophylline concentrations were lower at night than during the day (mean 9.4 +/- 0.9 versus 11.3 +/- 1.0 mg/l). With the single evening administration, serum theophylline concentrations were considerably higher at night (Cmax 16.3 +/- 1.4 mg/l) and the circadian variation of PEFR was significantly reduced. PEFR was higher during night and early morning (283 +/- 14 versus 217 +/- 11 l/min, P less than 0.005). During daytime in study II, PEFR values were slightly higher with theophylline than terbutaline. There was no significant difference in peak flow between either treatment during the night and early morning. However, additional use of inhaled beta-2-mimetics because of asthmatic attacks occurred more often during terbutaline (79 times in 8/10 patients) than theophylline treatment (29 times in 5/10 patients). Symptom scores, number of attacks and side-effects clearly favor the theophylline regimen. We conclude that for patients with nocturnal asthma a once-nightly dose of SR theophylline can be sufficient for stabilization of the airways.  相似文献   

16.
Two theophylline treatments were compared in a randomized, multiple-dose, crossover study on 20 patients present with nonallergic bronchial asthma. Both products (E = Euphyllin CR, A = Afonilum Retard) were capsules containing micropellets. They were administered according to the recommendations of the manufactures and differed in the total daily theophylline dose (642 mg versus 500 mg), the partition of this dose (1/3 in the morning and 2/3 in the evening versus equal amounts in the morning and evening) and the timing of the evening dose (2200 hr versus 2000 hr). The patients were off oral theophyllines at least 2 days prior to study onset and no other drugs were allowed to be administered during the testing periods. On the 4th day of each study period, serum theophylline concentrations (STC) and peak expiratory flow rate (PEF) were determined every 2 hr. Compared with the 24-hr PEF reference profile taken prior to study onset, both theophylline treatments produced a significantly higher 24-hr PEF average (mesor). Treatment E resulted in significantly higher mesor than A; in addition, the PEF amplitude relative to the mesor was reduced by treatment E when compared with placebo.  相似文献   

17.
In two double-blind, multiple-dose cross-over studies the therapeutic effects of SR theophylline preparations given once each night (mean 11.2mg/kg per day) versus twice daily in equal doses (mean 10.3 mg/kg per day) (study I) and SR-terbutaline in equal doses (mean 0.25 mg/kg per day) versus SR theophylline in unequally divided daily doses (mean 5.3 mg/kg morning dose, 10.6 mg/kg evening dose) study II) were compared in 19 patients with nocturnal asthma. At the end of each treatment period drug serum concentrations and PEFR were measured every 2 hr over a 24-hr period. With the twice-daily, equally divided regimen, serum theophylline concentrations were lower at night than during the day (mean 9.4 ±0.9 versus 11.3± 1.0mg/l). With the single evening administration, serum theophylline concentrations were considerably higher at night (Cmax16.3 ±1.4 mg/1) and the circadian variation of PEFR was significantly reduced. PEFR was higher during night and early morning (283 ±14 versus 217 ± 11 l/min, P< 0.005). During daytime in study II, PEFR values were slightly higher with theophylline than terbutaline. There was no significant difference in peak flow between either treatment during the night and early morning. However, additional use of inhaled β-2-mimetics because of asthmatic attacks occurred more often during terbutaline (79 times in 8/10 patients) than theophylline treatment (29 times in 5/10 patients). Symptom scores, number of attacks and side-effects clearly favor the theophylline regimen. We conclude that for patients with nocturnal asthma a once-nightly dose of SR theophylline can be sufficient for stabilization of the airways.  相似文献   

18.
This was an open-label study in 19 children aged 9–13 years, weighing 27–44 kg, with bronchial asthma. Twenty-four-hour steady-state concentrations of theophylline and its metabolites 1,3-dimethyl uric acid, 3-methyl xanthine and 1-methyl uric acid were assessed after daily dosing of 600 mg (ca18 mg/kg/day) of the sustainedrelease theophylline micro-pellet sprinkle system BY158K, for 4 days. The dosing regimen used was an unequal twice-daily dose of 200 mg in the morning after breakfast and 400 mg in the evening after dinner. Twenty-four-hour peak expiratory flow (PEF) profiles were compared before treatment and at steady-state, along with lung function parameters after bronchial provocation. Mean values±SD (n=16) of the steady-state characteristics were Cmin6.8±2.1 mg/1, Cmax14.5±4.8 mg/1 and Cav10.S±2.9 mg/1, the plateau time was 11.7±4.8 hr and peak-trough fluctuation and swing were 72±21 and 118±52%, respectively. There was an excellent reproducibility of theophylline pre-dose levels at corresponding time points of the 24-hr sampling period [r=0.864 (p< 0.001)]. Mean values±SD of the 24 hr average serum metabolite levels were 0.9±0.2 mg/1 for 1, 3-dimethyl uric acid, 0.6±0.1 mg/1 for 3-methyl xanthine and 0.4±0.1 mg/1 for 1-methyl uric acid. Lung function (n=17) following bronchial provocation, improved in 10 children after theophylline treatment of 4 days, remained stable in 2 patients and deteriorated in 5 patients. Serum theophylline profiles and PEF profiles ran largely in parallel over the 24-hr period. Six children exhibited typical theophylline induced side-effects, headache (n=3), nausea (n=4), dizziness (n=l), vomiting (n=4), sleep disturbances (n=1), pallor (n=1) and tremor(n=1), necessitating in 3 children one dose omission/reduction (n=2) or subsequent dose reduction (n=1). It has been shown that a twice daily dosing regimen with unequal doses of anhydrous theophylline (BY158K) is well suited to this population of fast metabolisers. The patients were well protected throughout the day, including the critical early morning hours.  相似文献   

19.
In six subjects with intrinsic asthma in clinical remission, time-structure of ventilatory parameters has been evaluated in order to evaluate: 1) which indexes present statistically significant circadian fluctuations; 2) if phase-shifts occur in comparison with normal subjects. After a period of synchronization of 7 days (L/D: 07.30-23.00; meal timing at 08.00, 13.00 and 20.30) all subjects have been studied by spirometry, flow-volume loop and Raw determination 6 times in a 24-hr period at constant intervals of 4 hrs. The results have been evaluated by macroscopic and microscopic analysis statistical significant fluctuations have been shown in these functional indexes: MEF50, Raw, SRaw, SGaw, FRC and RV; no phase-shifts occurred in comparison with normal subjects. On the contrary a circadian rhythm has not been shown in FVC, FEV1, and PEF. Therefore only the effort-independent test should be used to study correctly the bronchial tone.  相似文献   

20.
The aim of this study was to investigate circadian variation in concentrations of arachidonic acid(AA) metabolites in relation to the circadian pattern in bronchial patency. Blood samples were obtained at 4-hr intervals from 2000 of 1 day until 1400 of the next from 12 diurnally active asthmatic and six diurnally active non-asthmatic patients. Bloods were analyzed for the prostanoids thromboxane A2 (measured as stable metabolite 6-keto-PGF1a), PGE2, and PGF2a. Airways patency was assessed by self-measurement of peak expiratory flow (PEF). In asthmatics, circadian variation was detected in PEF as well as PGE2 and TXB2. The circadian trough of the PEF rhythm closely coincided with the circadian peak of the PGE2 and TXB2, rhythms. In the controls, the PEF was not circadian rhythmic. Of the AA metabolites only 6-keto-PGF1a exhibited 24-hr bioperiodicity in the controls. The controls exhibited a significantly higher circadian mean of PEF (P < 0.001), while the asthmatics had a lower 24-hr average PGE2 but greater mean TXB2/PGE2 ratio. The obstructive effect caused by the overall 24-hr deficiency of PGE2 in asthmatics is possibly amplified by the increased of TXB2 during the early morning hours. This dissociation of the temporal patterns in TXB, and PGE, levels over the 24 hr is discussed as a characteristic finding for asthmatics.  相似文献   

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