cholinophyllin and Asthma

Exercise-induced asthma (EIA) was provoked by standardized treadmill running for 6 minutes in 15 asthmatic children. The tests were carried out after the administration of a placebo, salbutamol, sodium cromoglycate, choline theophyllinate, and atrophine methonitrate aerosol in randomized fashion on different days. The mean post-exercise percent fall in peak expiratory flow rate was 45-2, 4-1, 19-6, 18-3, and 24-9 respectively. The proportion of children having significant amelioration of their EIA compared with those taking the placebo was 100% for salbutamol, 80% for cromoglycate and theophyllinate, and 60% for atropine. Salbutamol, choline theophyllinate, and atropine were bronchodilators at rest whereas cromoglycate was not, and the ability to suppress EIA was unrelated to bronchodilator effect. Even after bronchodilatation at rest, further broncho-dilatation occurred during the exercise period.

Topics: Adolescent; Airway Obstruction; Albuterol; Asthma; Atropine Derivatives; Bronchodilator Agents; Child; Child, Preschool; Choline; Clinical Trials as Topic; Cromolyn Sodium; Humans; Peak Expiratory Flow Rate; Physical Exertion; Placebos; Theophylline

Topics: Adult; Aminophylline; Asthma; Biological Availability; Bronchodilator Agents; Choline; Excipients; Female; Humans; Male; Middle Aged; Random Allocation; Respiratory Function Tests; Theophylline

Nocturnal wheeze is common in patients with asthma, and slow release theophyllines may reduce symptoms. As theophyllines are stimulants of the central nervous system the effect of 10 days' twice daily treatment with sustained release choline theophyllinate or placebo on symptoms, overnight bronchoconstriction, nocturnal oxygen saturation, and quality of sleep were studied in a double blind crossover study in nine stable patients with nocturnal asthma (five men, four women, age range 23-64 years; forced expiratory volume in one second (FEV1) 0.85-3.8 1; vital capacity 1.95-6.1 1). When treated with the active drug all patients had plasma theophylline concentrations of at least 28 mmol/l (5 micrograms/ml) (peak plasma theophylline concentrations 50-144 mmol/l (9-26 micrograms/ml]. Morning FEV1 was higher when treated with sustained release choline theophyllinate (2.7 (SEM 0.3) 1) than placebo (2.1 (0.3) 1) (p less than 0.01). Both daytime and nocturnal symptoms were reduced when the patients were treated with sustained release choline theophyllinate and subjective quality of sleep was improved (p less than 0.002). When treated with the active drug, however, quality of sleep determined by electroencephalography deteriorated with an increase in wakefulness and drowsiness (p less than 0.05) and a reduction in non-rapid eye movement sleep (p less than 0.005). Treatment with choline theophyllinate had no effect on either the occurrence or the severity of transient nocturnal hypoxaemic episodes or apnoeas or hypopnoeas. In conclusion, sustained release choline theophyllinate prevents overnight bronchoconstriction, but impairs quality of sleep defined by electroencephalography.

Topics: Adult; Aged; Asthma; Choline; Clinical Trials as Topic; Delayed-Action Preparations; Double-Blind Method; Forced Expiratory Volume; Humans; Middle Aged; Random Allocation; Sleep; Theophylline

The role of the anticholinergic drug, ipratropium bromide, in maintenance antiasthmatic therapy was evaluated in a double-blind crossover trial of three bronchodilator regimens: (1) inhaled ipratropium, placebo, and oral oxtriphylline; (2) inhaled fenoterol, placebo, and oral oxtriphylline; and (3) both inhaled ipratropium and fenoterol plus oral oxtriphylline. Twenty-two asthmatics were treated with all three regimens, each for 1 mo, allocated in random sequence. On the first and last treatment days of each month, spirometric measurements were performed before and 0.5, 1, 2, 3, 4, and 6 hr after administration of the test drugs. On the first treatment day of each month, all regimens produced significant bronchodilatation at 30 min after dose, an improvement that declined between 3 and 6 hr after dose. After continuous administration for 1 mo the two combinations employing fenoterol showed a decline in bronchodilator responsiveness from the initial treatment day, measured as the level of response (V50) or duration of response (FEV1, VC). Ipratropium plus oxtriphylline showed no such decline, suggesting the development of tolerance to long-term administration of fenoterol. Overall benefit at the end of 1 mo, measured as the area under the curves of FEV1, VC, or V50 vs time after dose, was greatest for the triple drug regimen. There were no differences in heart rate, blood pressure response, or side effects among the three treatments. It is concluded that when the anticholinergic drug ipratropium is administered concurrently with an inhaled beta 2 agonist and an oral theophylline derivative, increased bronchodilatation occurs with no detectable additional side effects.

Topics: Adolescent; Adult; Aged; Asthma; Blood Pressure; Choline; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Fenoterol; Heart Rate; Humans; Ipratropium; Male; Middle Aged; Parasympatholytics; Respiratory Function Tests; Sympathomimetics; Theophylline

Fifty clinically stable patients with asthma on maintenance theophylline therapy, mean dose of 15 mg kg-1 per day, were switched to an equivalent dose (X 1.56) of oxtriphylline SA for seven doses. All subjects remained clinically stable after the change during the study period. Oxtriphylline SA appears to be useful for the maintenance treatment of asthma and can be safely substituted for other theophylline maintenance regimens.

Topics: Adult; Aged; Aminophylline; Asthma; Choline; Clinical Trials as Topic; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Theophylline

A comparison of pharmacokinetics and therapeutic effects of a standard oral theophylline preparation (Choline Theophyllinate) and controlled release aminophylline (Phyllocontin) was made in two parallel double blind trials in 25 children with chronic asthma. Fourteen children entered a double blind cross-over trial; the remaining 11 were allocated to a parallel trial with no change of theophylline preparation throughout. Sustained plasma theophylline levels were observed with the controlled release preparation in contrast to the low morning levels obtained with Choline Theophyllinate. No significant differences were found for peak theophylline levels, morning or evening peak flow rates or required access to other bronchodilators. However nocturnal symptoms were significantly reduced and daytime activity scores improved (P less than 0.05) on the controlled release preparation. The sustained plasma theophylline levels found in children taking the controlled release aminophylline may have provided a small but useful therapeutic advantage over the standard preparation.

Topics: Adolescent; Aminophylline; Asthma; Child; Choline; Chronic Disease; Double-Blind Method; Female; Humans; Kinetics; Male; Theophylline

Topics: Adolescent; Adult; Aminophylline; Asthma; Bronchodilator Agents; Choline; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Theophylline

Topics: Adult; Airway Resistance; Aminophylline; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Choline; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Theophylline

The bioavailability of three different theophylline tablets (microcrystallinic theophylline, Theolair, Nuelin, 3M Riker), choline theophyllinate as a new film-coated tablet (Teovent, Ferrosan, Sweden) and theophyllaminopropanol (Oxyphylline, Draco, Sweden) was investigated in eight adult asthmatics and a randomized, double-blind, cross-over study. Effects on ventilatory capacity (FEV1 and FVC), circulation (heart rate and blood pressure) and skeletal muscle tremor were followed. The theophylline concentration was determined by gas chromatography. Forty-five minutes after theophylline administration the plasma concentrations were almost the same for all four formulations. The bioavailability was also almost identical. The half-life for intravenous theophylline in these asthmatics was 7.4 +/- 0.64. The three tablet formation had equal effect on FEV1 and the effect was sustained throughout the 6-h period. Six hours after theophylline administration five terbutaline inhalations induced the same further increase in FEV1. The results indicate that theophylline alone has only a moderate acute bronchodilating effect at recommended plasma concentrations but gives a good effect when combined with inhaled beta 2-adrenostimulants.

Topics: Administration, Intranasal; Administration, Oral; Asthma; Biological Availability; Bronchodilator Agents; Choline; Drug Therapy, Combination; Forced Expiratory Volume; Heart Rate; Humans; Kinetics; Terbutaline; Theophylline; Tremor; Vital Capacity

Exercise-induced asthma (EIA) was provoked by standardized treadmill running for 6 minutes in 15 asthmatic children. The tests were carried out after the administration of a placebo, salbutamol, sodium cromoglycate, choline theophyllinate, and atrophine methonitrate aerosol in randomized fashion on different days. The mean post-exercise percent fall in peak expiratory flow rate was 45-2, 4-1, 19-6, 18-3, and 24-9 respectively. The proportion of children having significant amelioration of their EIA compared with those taking the placebo was 100% for salbutamol, 80% for cromoglycate and theophyllinate, and 60% for atropine. Salbutamol, choline theophyllinate, and atropine were bronchodilators at rest whereas cromoglycate was not, and the ability to suppress EIA was unrelated to bronchodilator effect. Even after bronchodilatation at rest, further broncho-dilatation occurred during the exercise period.

Topics: Adolescent; Airway Obstruction; Albuterol; Asthma; Atropine Derivatives; Bronchodilator Agents; Child; Child, Preschool; Choline; Clinical Trials as Topic; Cromolyn Sodium; Humans; Peak Expiratory Flow Rate; Physical Exertion; Placebos; Theophylline

Fifteen Chinese subjects with stable asthma were given asymmetric doses of slow-release choline theophyllinate (Theobret) according to body weight; patients under 60 kg (132 lb) received 180 mg at 9 AM and 360 mg at 9 PM for six days (period 1), followed by 180 mg at 1 PM and 360 mg at 9 PM for six days (period 2); for those over 60 kg, the regimen was the same, except that they received 270 mg during the daytime and 540 mg at night. At the end of each period of treatment, concentration of theophylline was measured over 24 hours. Five patients experienced side effects, and two of these were withdrawn from the study. In the remaining 13 patients, optimal concentrations of the drug were attained during most of the 24 hours, and there were only minor pharmacokinetic differences between the two periods of treatment. Compared with observations before treatment, the total symptom score was unchanged, but the peak expiratory flow rate in the morning and evening improved, and the use of inhaled bronchodilator drugs decreased significantly. There was a trend towards progressive improvement as the duration of treatment increased, suggesting that the therapeutic effect of theophylline may lag behind the attainment of optimal concentrations. We conclude that asymmetric dosing regimens of slow-release theophylline are effective and rational in maintenance therapy for asthma and that lower total daily dosages may be more appropriate in Chinese patients when compared to those recommended for white subjects.

Topics: Adult; Asthma; Bronchodilator Agents; China; Choline; Delayed-Action Preparations; Drug Administration Schedule; Female; Hong Kong; Humans; Male; Middle Aged; Theophylline

The day and night pharmacokinetics of assymetrical doses of slow release choline theophyllinate (Sabidal SR 270) were compared at day 1 and at day 4 of treatment when steady state had been achieved. Ten patients with chronic asthma were given oral choline theophyllinate 424 mg at 09.00 h and 848 mg at 21.00 h for 4 days. At regular intervals during day 1 and day 4 of treatment theophylline concentrations were measured in plasma and dried blood spots by fluorimmunoassay. Theophylline concentrations measured from dried blood spots were slightly lower than those in plasma, the difference remaining constant at all time points during day 1 and day 4 of treatment. On day 1 the mean peak plasma theophylline concentration was 5.4 +/- 1.0 (+/- s.e. mean) micrograms ml-1 4 h after the morning dose and 11.2 +/- 1.6 micrograms ml-1 4 h after the evening dose which were significantly (P less than 0.01) different. Similarly the areas under the plasma theophylline concentration-time curves at night were significantly (P less than 0.001) greater than those observed during the day. During day 4 mean peak plasma concentrations of theophylline after the morning and larger evening dose were 13.2 +/- 1.3 and 12.1 +/- 1.4 micrograms ml-1 respectively, which were not significantly different. No significant difference was observed between the areas under the plasma theophylline concentration-time curves during the day and at night. However the post-dose time to peak was significantly delayed at night (6 h) compared to the morning (2 h, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Aged; Asthma; Blood Stains; Bronchodilator Agents; Choline; Delayed-Action Preparations; Drug Administration Schedule; Female; Humans; Kinetics; Male; Middle Aged; Theophylline; Time Factors

Topics: Adult; Asthma; Choline; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Theophylline

We studied 16 adults with chronic bronchial asthma by measuring the plasma theophylline concentrations and evaluating clinically the control of asthma following oral administration of choline theophyllinate (CT) and a sustained-release theophylline preparation (SRT). All 16 patients were studied in 3 one-weekly phases. These patients received CT 200 mg t.i.d. during the 1st week, no theophylline during the 2nd week and SRT 250 mg 12-hourly during the 3rd week. All other anti-asthmatic medications were maintained during the study. After the night dose of a theophylline preparation, the mean plasma trough concentration the next morning was significantly higher for SRT (9.4 mcg/ml +/- SEM 1.0) than for CT (3.6 mcg/ml +/- SEM 0.6). The mean plasma peak concentration after the morning dose was also significantly higher for SRT (11.5 mcg/ml +/- SEM 1.0) than for CT (7.4 mcg/ml +/- SEM 1.0), The mean forced expiratory volume in one second (FEV1) obtained during SRT treatment was significantly higher than during CT treatment. There was no significant difference between FEV1 measured at trough concentrations during CT treatment and during the period without theophylline. The patients had fewer symptoms of asthma and fewer side-effects from theophylline during the week they received SRT compared with the week they received CT. In this study, using the conventional dosage schedule as practised in Singapore, SRT has distinct advantages over CT in the treatment of chronic asthma.

Topics: Administration, Oral; Adult; Aged; Asthma; Bronchodilator Agents; Choline; Delayed-Action Preparations; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Theophylline

The effect of inhaled verapamil and gallopamil (estimated dose 3 mg) was studied in 10 patients with exercise-induced asthma. Saline was used as a control. Verapamil and gallopamil modified exercise-induced asthma in 8 of the 10 patients and the degree of inhibition with both the drugs was comparable. Gallopamil, which is a more potent vascular smooth muscle calcium antagonist when compared to verapamil, failed to show a greater protective effect in exercise-induced asthma in the patients studied.

Topics: Administration, Oral; Adolescent; Adult; Asthma; Blood Pressure; Choline; Forced Expiratory Volume; Humans; Middle Aged; Pulse; Rectum; Spirometry; Theophylline; Vital Capacity

Topics: Adolescent; Adult; Aged; Asthma; Biological Availability; Child; Choline; Female; Humans; Male; Middle Aged; Theophylline

Topics: Administration, Oral; Aminophylline; Asthma; Bronchodilator Agents; Child; Child, Preschool; Choline; Humans; Injections, Intravenous; Singapore; Theophylline

Average peak concentrations of theophylline in plasma (range, 15 mumol/L) were not significantly different when Nuelin, Brondecon and Choledyl tablets were administered to healthy subjects. The fraction of the theophylline dose absorbed from these preparations was comparable (range, 0.82 to 0.90). In contrast, the absorption of theophylline was significantly different (P < 0.001) when the times to reach peak theophylline concentration were compared. Mean peak theophylline concentrations were achieved 1.5 hours after administration of either Nuelin or Brondecon tablets and nine hours after Choledyl administration. Nuelin and Brondecon are considered to be bioequivalent. Choledyl may be used when side effects caused by rapid theophylline absorption are to be avoided.

Topics: Absorption; Adolescent; Adult; Asthma; Biological Availability; Choline; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Female; Humans; Kinetics; Random Allocation; Theophylline; Time Factors

As follow-up to earlier studies done on the pharmacokinetics of theophylline preparations in young children, an alcohol-free oxtriphylline syrup preparation was studied. Oxtriphylline syrup demonstrated no appreciable change in the pharmacokinetic parameter of half-life in this young age group. Therapeutic dose relationship were studied in conjunction with trough level measurements. Patient acceptance of this preparation is judged to be excellent.

Topics: Asthma; Child, Preschool; Choline; Dose-Response Relationship, Drug; Ethanol; Female; Half-Life; Humans; Infant; Kinetics; Male; Solutions; Taste; Theophylline

Topics: Adolescent; Asthma; Biomedical Research; Child; Choline; Drug Therapy; Expectorants; Glycerol; Guaiacol; Guaifenesin; Humans; Infant; Preventive Medicine; Theophylline; Toxicology

Topics: Adolescent; Asthma; Bronchitis; Bronchitis, Chronic; Child; Choline; Geriatrics; Guaifenesin; Humans; Sympathomimetics; Theophylline

Topics: Asthma; Bronchitis; Bronchodilator Agents; Choline; Geriatrics; Guaiacol; Humans; Pulmonary Emphysema; Respiratory Tract Diseases; Tablets; Theophylline

Topics: Asthma; Bronchodilator Agents; Child; Choline; Expectorants; Geriatrics; Guaiacol; Respiratory Function Tests; Theophylline; Toxicology

Topics: Asthma; Choline; Double-Blind Method; Guaifenesin; Humans; Theophylline

Topics: Asthma; Bronchiectasis; Bronchitis; Choline; Cough; Double-Blind Method; Guaifenesin; Pulmonary Emphysema; Respiratory Function Tests; Theophylline; Toxicology

Topics: Asthma; Child; Choline; Humans; Theophylline

Topics: Asthma; Choline; Humans; Menstruation; Theophylline