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  • 1
    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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  • 2
    ISSN: 1432-1041
    Keywords: hydralazine ; indomethacin ; normal subjects ; heart rate ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Indomethacin 100 mg/day or matching placebo was given for 2.5 days to 9 healthy volunteers in a double-blind cross-over study, followed by an intravenous injection of 0.2 mg/kg of hydralazine. Compared to placebo, indomethacin produced no statistically significant change in pulse rate or blood pressure in both standing and supine positions. Hydralazine injection was followed by a statistically significant fall in lying and standing diastolic pressure and a rise in lying and standing pulse after both indomethacin and placebo pretreatments. There were no significant differences in these effects following indomethacin compared to placebo pretreatment. These results do not support the hypothesis that endogenous prostaglandins are involved in the mechanism of action of hydralazine.
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  • 3
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; slow release formulations ; bronchial asthma ; pharmacokinetics ; methods of comparison
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of two slow release theophylline preparations “Theo-Dur” (T) containing theophylline only and “Phyllocontin” (P) containing aminophylline have been compared in 12 patients with asthma. Each patient received both treatments in random order. The dose of treatment administered 12 hourly was increased or decreased to produce plasma theophylline concentrations of 10–20 mg/l at clinic visits normally 7 to 8 h after dosing. Pharmacokinetic studies were carried out after at least one week's treatment with this dose. After the first study day patients were crossed over to the second treatment at a dosage providing a similar amount of theophylline. They returned for a second study day after at least one week. Comparison of the dose corrected AUC, time to peak concentrations, within patient coefficients of variation (CV), number of concentration time points falling within 25% of Cmax and percentage fluctuations in plasma concentration showed no significant differences between the two preparations.
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  • 4
    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.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: urapidil ; volunteers isoproterenol dose response analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Urapidil is an antihypertensive vasodilator agent whose pharmacological action in man has not yet been fully defined. We have assessed the beta blocking activity of urapidil 15 mg and 30 mg i.v. in a single blind study of 10 healthy male volunteers. Urapidil at plasma concentrations in the same range as those shown to have antihypertensive affect did not significantly attenuate the chronotropic effect of isoproterenol. Propranolol 5 mg iv, the positive control, significantly shifted the isoproterenol dose-response curve to the right. We describe a new method of analyzing incomplete dose response curves whereby a linear terminal segment can be reproducibly defined.
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  • 6
    ISSN: 1432-1041
    Keywords: nifedipine ; nisoldipine ; nitrendipine ; haemodynamics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nifedipine (10 mg), nisoldipine (10 mg) and nitrendipine (20 mg) were given orally to 8 normal volunteers in a placebo controlled, double blind, crossover study. Blood pressure (BP), pulse (P) and systolic time intervals (STI) were recorded at time 0, 30, 60, 90, 120 min after drug administration. Adverse effects were also recorded. There was a fall in BP, pre-ejection time (PEP), PEP/LVET (left ventricular ejection time) and electro-mechanical systole index (QS2 index), and a rise in LVET index in response to the three active drugs compared with placebo. All active drugs, but not placebo, were associated with adverse effects.
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  • 7
    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; clearance ; age ; adults ; elderly ; normal subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifty three subjects (31 normal volunteers and 22 patients with asthma) between the ages of 20 and 87 years had their theophylline clearance measured. Volume of distribution (V) and terminal elimination half-life (t1/2) were also calculated in the volunteers who received i.v. theophylline. Although patients tended to have higher clearance values than volunteers, in both groups the oldest third had the lowest clearances. For the combined group (corrected for the patient effect) the oldest third (mean age 70 years) had a mean clearance of 0.53 versus 0.72 for the middle third (mean age 47 years) and 0.73 ml/min/kg CBW for the youngest third (mean age 26 years). There was no statistically significant age related change in V/kg CBW but t1/2 did rise with increasing age. Thus, although clearance does not fall with increasing age during younger adult life, there is a fall during late adult life becoming apparent in the seventh, eighth and ninth decades.
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  • 8
    ISSN: 1432-1041
    Keywords: Key words Methylxanthines ; Psychomotor performance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The aim of this study was to investigate the dose-response relationship for psychomotor performance, caffeine and theophylline in healthy elderly volunteers. Methods: In a randomized, double-blind, placebo-controlled, six-period cross-over study we compared the effect of three doses of theophylline (predicted peak concentrations of 3, 6 mg · l−1 and 12 mg · l−1), two doses of caffeine (predicted peak concentrations of 4.5 mg · l−1 and 9 mg · l−1) and placebo on ten healthy elderly volunteers. Psychomotor performance was measured using a continuous attention task, symbol digit substitution test and choice reaction time. Subjective effects were assessed using visual analogue scales. Following drug administration, subjects received the test battery at 30-min intervals, up to 150 min. Maximum and mean effects from baseline on each variable were included in the analysis. Results: Significant improvement on the continuous attention task was seen at the lowest concentration of caffeine and theophylline used, while at higher concentrations there was a non-significant trend towards placebo scores. There was little effect of either drug on the subjective effects measured by visual analogue scales. Conclusion: Caffeine and theophylline increase psychomotor performance measures of attention at low plasma concentrations in healthy elderly volunteers. This effect is not increased by higher drug concentrations and there is trend towards a return to placebo scores. The lack of effect of both caffeine and theophylline on subjective measures is consistent with previous studies of caffeine in the elderly.
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  • 9
    ISSN: 1432-1041
    Keywords: Medifoxamine ; pharmacokinetics ; pharmacodynamics ; elderly volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and psychomotor effects of medifoxamine, a 5 HT reuptake inhibitory antidepressant, were studied in healthy elderly volunteers after single and multiple dosing. The elimination half life (t1/2z) after single doses of 300 mg was 2.8 h — almost identical to that found in young volunteers. After seven days of dosing at 100 mg three times daily the mean corrected AUC after 300 mg significantly increased from 1.04 to 1.34 mg.h.l−1 and t1/2z increased to 4.0 h (NS). There were no significant changes in critical flicker fusion frequency, symbol digit substitution, continuous attention or choice reaction times.
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  • 10
    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; personality measures ; pharmacokinetics ; volunteers ; patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirteen volunteers received an iv dose of theophylline followed by blood sampling for 8 h to calculate pharmacokinetic parameters. Ten patients with asthma undergoing chronic dosing with slow release aminophylline underwent 12 h of blood sampling to calculate theophylline clearance. Both groups completed an Eysenck Personality Inventory (EPI) from which was derived scores for neuroticism (N) and extroversion (E). Using multiple regression analysis no independent effect of either N or E score on theophylline clearance or half-life could be demonstrated.
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