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Biomedical subjects

G Kaik

Publications and source records attributed to G Kaik.

At least 19 recordsLinked to original sources
PubMed1995

Effect of solution and suspension type aerosol of formoterol on tremor response and airways in patients with asthma.

BACKGROUND: Aerosol delivery and deposition to the oropharynx and the lungs have been found to be different for solution-type and suspension-type metered-dose aerosols used for treatment of asthma. We investigated possible differences in clinical effects between solution and suspension metered-dose formoterol aerosols. METHODS: A total of 24 patients with asthma (forced expiratory volume in 1 second, < or = 70% predicted) inhaled single doses (12 micrograms or 24 micrograms) of formoterol solution and suspension so that we could investigate the immediate tremor, airway, and cardiovascular responses in a randomized, double-blind, crossover trial. Fenoterol suspension aerosol (400 micrograms) was used for comparison (single-blind, poststudy, nonrandomized administration). Fenoterol (400 micrograms) as a rescue medication was inhaled after 120 minutes on each of the 5 study days. RESULTS: The order of mean (+/- SEM) maximum tremor acceleration was as follows: 12 micrograms formoterol solution (67.92 +/- 4.54 cm x sec-2) < 24 micrograms solution (73.46 +/- 4.51 cm x sec-2) < 12 micrograms suspension (80.87 +/- 5.08 cm x sec-2) < fenoterol (84.13 +/- 4.21 cm x sec-2) < 24 micrograms formoterol suspension 88.54 +/- 6.26 cm x sec-2). Maximum increase in specific airway conductance ranged from 0.48 +/ 0.03 to 0.55 +/- 0.04 sec-1 x kPa-1 for all drugs (p > 0.05). No change in cardiovascular parameters occurred (p > 0.05). CONCLUSION: No difference in the bronchial response to either formulation of formoterol was found. Tremor response to suspension aerosol (24 micrograms > 12 micrograms) was higher than that to solution aerosol (24 micrograms > 12 micrograms), indicating possible differences in systemic absorption because of a different deposition pattern. Rescue medication demonstrated systemic effects on tremor that were additive to those of formoterol.

Adult↗
PubMed1994

Osmotic release oral drug delivery system of metoprolol in hypertensive asthmatic patients. Pharmacodynamic effects on beta 2-adrenergic receptors.

This study investigated the effects of an osmotic release oral drug delivery system of metoprolol on the changes induced by cumulative doses of inhaled salbutamol on bronchomotor tone, skeletal muscle, and the circulatory system after single (day 1) and multiple (day 7) dosing in 18 hypertensive asthmatic patients (forced expiratory volume in 1 second > 50% predicted; diastolic blood pressure > 90 mm Hg). The patients were given 14/190 mg metoprolol, 100 mg atenolol, and placebo once daily for a 7-day period each in a randomized, double-blind, crossover design. At the estimated time of peak plasma concentrations, cumulative doses of salbutamol (12.5, 37.5, 112.5, 412.5, 812.5, and 1612.5 micrograms) were applied every 20 minutes. Specific airway conductance, finger tremor amplitude, heart rate, and blood pressure were registered at baseline and at each dose increment. The slopes of the salbutamol dose-response curves of specific airway conductance did not differ on day 1 (P > .05). On day 7, atenolol caused a shift of the dose-response curves of specific airway conductance to the right (P < .05), whereas metoprolol was indistinguishable from placebo (P > .05). The median cumulative salbutamol concentrations causing a 50% increase in specific airway conductance were 416 and 384 micrograms (days 1 and 7, respectively) for placebo, 594 and 444 micrograms for metoprolol, and 562 and 1419 micrograms for atenolol. The median cumulative salbutamol concentrations causing a 35% increase in tremor were 732 and 706 micrograms for placebo, 812 and 1213 micrograms for metoprolol, and 797 and 1323 micrograms for atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1993

Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma.

The airway and tremor response and cardiovascular and hypokalemic effects of single doses of inhalative fenoterol dry powder capsules (0.4 mg) were compared with the fenoterol metered dose inhaler (0.4 mg) and colforsin (forskolin) dry powder capsules (10.0 mg), a direct activator of the adenylate cyclase system, in 16 patients with asthma. Subjects (FEV1 < or = 60% predicted) were investigated in a randomized, double-masked, placebo-controlled, four-period, crossover trial for a 120 minute period. All active drugs caused a significant increase in specific airway conductance (p < 0.05); the order of potency (mean +/- SEM maximum increase from baseline) was fenoterol metered dose inhaler (0.51 +/- 0.06 sec-1 x kPa-1), fenoterol dry powder capsules (0.49 +/- 0.07), and colforsin dry powder capsules (0.30 +/- 0.03). A marked increase in finger tremor amplitude resulted after fenoterol metered dose inhaler only (62.93% +/- 10.21%; p < 0.05) in contrast to fenoterol dry powder capsules (15.84% +/- 4.35%; p < 0.05) and colforsin dry powder capsules (12.87% +/- 10.44%; p > 0.05). A decrease in plasma potassium was found after fenoterol (metered dose inhaler > dry powder capsules; p < 0.05). In conclusion, fenoterol dry powder capsules caused less tremor response and hypokalemic effects than the metered dose inhaler, although the bronchodilator capacity was similar. Colforsin dry powder capsules resulted in a measurable bronchodilatation in patients with asthma.

Administration, Inhalation↗
PubMed1993

Assessment of beta-adrenergic receptor blockade after isamoltane, a 5-HT1-receptor active compound, in healthy volunteers.

This study investigated the effects of isamoltane on the changes induced by cumulative doses of inhaled albuterol (salbutamol) on bronchomotor tone, skeletal muscle, circulatory system, and metabolism after single (day 1) and multiple dosing (day 7) in 15 healthy subjects. The volunteers were given placebo, 4 mg isamoltane, 10 mg isamoltane, or 20 mg propranolol over a 7-day period in a randomized, double-blind, crossover design. The greatest attenuation in albuterol-induced beta-adrenergic receptor responses occurred with propranolol. The median provocative dose of albuterol causing a 50% increase in specific airway conductance was 337 and 315 micrograms (day 1 and day 7, respectively) for placebo, 336 and 322 micrograms for 4 mg isamoltane, 344 and 389 micrograms for 10 mg isamoltane, and 667 and 652 micrograms for propranolol. The provocative dose of albuterol producing a 35% increase in tremor was 464 and 539 micrograms (day 1 and day 7, respectively) for placebo, 1122 and 1270 micrograms for 4 mg isamoltane, 1612 and > 1612 micrograms for 10 mg isamoltane, and > 1612 and > 1612 micrograms for propranolol. On day 5 of each period an exercise test was performed. Propranolol reduced exercise heart rate by 11% (compared with placebo), 10 mg isamoltane reduced heart rate by 5%, and 4 mg isamoltane reduced heart rate by 1%. In conclusion, low-dose isamoltane caused measurable systemic effects on both beta 2- and beta 1-adrenergic receptors, and the dose-dependent blockade on beta 2-receptors of skeletal muscle was more clear than the attenuation of exercise heart rate.

Adrenergic beta-Antagonists↗
PubMed1991

Assessment of systemic effects of different ophthalmic beta-blockers in healthy volunteers.

Systemic beta-blockade after single doses of ophthalmic beta-blockers (one drop in each eye) was investigated in healthy volunteers in two randomized, double-blind, crossover, placebo-controlled studies. beta-Blockade was evaluated by displacement of the bronchodilator (specific airway conductance), positive chronotropic (heart rate), and tremorogenic (finger tremor amplitude) dose-response curve for inhaled isoproterenol. In study 1, 0.5% betaxolol, 0.6% metipranolol, and 0.5% timolol were tested in 16 subjects. Compared with placebo, all beta-blockers resulted in a significant systemic beta-blockade (p greater than 0.05); the increasing order of potency was betaxolol, metipranolol, and timolol. In study 2, 2% butylamino-phenoxy-propanol-acetate (BPPA; a noncardioselective but topically oculoselective drug) and 1% timolol were investigated in 12 subjects. Placebo and BPPA showed no differences (p greater than 0.05), whereas timolol resulted in a significant beta-blockade (p less than 0.05). Topical oculoselectivity is an important aspect of drug safety of beta-blocking eyedrops. Measure of tremor is appropriate to evaluate beta 2-blockade.

Adrenergic beta-Antagonists↗
PubMed1990

Pulmonary effects of long-term beta 2-blockade in healthy subjects: comparative study of metoprolol OROS.

The effects on airway response of metoprolol OROS (oral osmotic) and three other long-acting beta-adrenoceptor blockers were studied. This was a placebo-controlled, randomized, five-period, single-blind, crossover trial in 15 healthy volunteers. Bronchial beta-blockade was estimated as the displacement of the salbutamol bronchodilator response of specific airway conductance (SGAW) measured by whole-body plethysmography. Metoprolol OROS (14/190 mg), slow-release (SR) metoprolol (200 mg), atenolol (100 mg), long-acting (LA) propranolol (160 mg), and placebo were given once daily for 7 days. Inhaled salbutamol was administered at peak drug levels in cumulative doses of 12.5 to 800 micrograms on day 5 and in a single dose of 400 micrograms on day 7. On day 5, salbutamol induced significant increases in SGAW in each treatment group. SGAW increased after the single dose of salbutamol on day 7 in all groups and then declined steadily. The highest values were found after placebo and metoprolol OROS, with smaller increases after SR metoprolol, atenolol, and LA propranolol, the latter showing the smallest increase. Therefore, it would appear that under steady-state conditions, beta 2-bronchial receptors are least blocked by metoprolol OROS, followed by SR metoprolol, atenolol, and LA propranolol.

Administration, Oral↗
PubMed1990

Dose related protective effect of azelastine on histamine induced bronchoconstriction in extrinsic asthma.

The effect of single oral doses of the antiallergic agent azelastine hydrochloride (1.1, 2.2 and 4.4 mg) was compared to placebo on airway response to histamine challenge in 12 asymptomatic extrinsic asthmatics with proven bronchial hyperresponsiveness to inhaled histamine in a randomized double-blind crossover trial. All doses of azelastine resulted in a significant protection compared to placebo. The effects of 2.2 and 4.4 mg were equivalent and superior compared to 1.1 mg. A naturally small but statistically significant bronchodilator effect was observed 4 h after the two higher doses of azelastine. Tiredness was reported by two patients, the symptom occurred following each placebo and the active drug.

Airway Resistance↗
PubMed1989

[Clinico-pharmacologic study of a new sustained-release oral salbutamol preparation in patients with obstructive airway disease].

A new sustained release preparation of oral salbutamol (8 mg) was compared to salbutamol (8 mg) and placebo in 15 patients suffering from chronic obstructive airways disease in a randomized double-blind cross-over trial. Changes in airways resistance and amplitude of finger tremor as well as subjective assessment of side effects (tremors, unrest, palpitations) revealed a longer lasting effect following the sustained release preparation of salbutamol.

Adult↗
PubMed1988

Cardioselectivity of cetamolol compared with atenolol and nadolol.

The selectivity of the beta-adrenoceptor blockade produced by single oral doses of cetamolol, atenolol, and nadolol was compared in normal male subjects. Study 1 established the dose at which each drug provides equivalent beta-1 blockade. Beta-1 blockade was estimated using the degree of inhibition of the increased heart rate (HR) response to graded exercise. Cetamolol (30 mg), atenolol (100 mg), and nadolol (80 mg) all attenuated the HR response to a comparable extent. This result established that the dose ratio of cetamolol:atenolol:nadolol of 1.00:3.33:2.67 provides equipotent beta-1 blockade. This ratio of doses was used in Studies 2 and 3 to evaluate the antagonism of beta-2-mediated responses to titrated doses of intravenous isoproterenol (ISO) by low and high doses of each drug. Beta-2 blockade was assessed using the attenuation of ISO-induced reductions in diastolic blood pressure (DBP) in Study 2 and ISO-induced increases in specific airway conductance (sGAW) in Study 3. For within drug comparisons, antagonism of the HR increase induced by ISO (a response mediated by both beta-1 and beta-2 receptors) was also examined. Treatments included cetamolol (15 and 60 mg), atenolol (50 and 200 mg), and nadolol (40 and 160 mg in Study 2; 40 mg only in Study 3). All drugs tested suppressed the HR, DBP, and sGAW responses to ISO, and this blockade was dose dependent. Cetamolol and nadolol produced approximately equipotent beta-1 blockade, whereas cetamolol at both doses produced a less potent beta-2 blockade. Atenolol antagonized ISO effects on all parameters less than either cetamolol or nadolol. Quantitative cardioselectivity indices revealed that cetamolol 60 mg was the most cardioselective and nadolol 40 mg the least. Data from the three studies demonstrate that cetamolol is cardioselective relative to nadolol and that, in contrast to atenolol, cardioselectivity appears to increase at the higher dose.

Acetamides↗
PubMed1986

[Protective effect of forskolin in acetylcholine provocation in healthy probands. Comparison of 2 doses with fenoterol and placebo].

Forskolin, a potent adenylate cyclase activating diterpene-derivative, isolated from the Indian plant Coleus forskohlii, was tested double-blind and cross-over in 12 healthy volunteers (nonsmokers) by whole body plethysmography. All drugs were administered by metered dose inhalers. The bronchodilating effect (after 5 minutes) was as good as following fenoterol. At the beginning (after 3 and 5 minutes) the protective effect against inhaled acetylcholine was as good as following fenoterol while later on (after 15 and 30 minutes) fenoterol resulted in a stronger action.

Acetylcholine↗
PubMed1984

[A single dose of theophylline in the evening in chronic obstructive airway disease. Serum concentration and lung function parameter].

In 12 patients with long-standing obstructive respiratory disease, the nocturnal Theophylline plasma levels were investigated after the administration in the evening, of 600 or 800 mg respectively Theophylline given in the form of sustained-release tablets (Uniphyllin), measurements being made on the first, 4th and 5th day of the study. Hourly plasma level measurements were made in the critical period between 4.00 and 8.00 hours. Already on the first study day, Theophylline plasma concentrations were higher than 10 micrograms/ml 5 to 11 hours after medication; on days 4 and 5, corresponding values were achieved after 3 hours. On these days, the course of the curve was virtually identical. Only very small standard deviations were found. Seven hours after medication, the plasma levels of Theophylline were at a peak. On average, this was 14.4 micrograms/ml on day 1, 18.1 micrograms/ml on day 4, and 17.7 micrograms/ml on day 5. Prior to the next dose of Theophylline at 21.00 hours, Theophylline plasma levels of 6.6 and 6.4 micrograms/ml were measured on days 4 and 5, respectively. These figures were thus appreciably above 5 micrograms/ml even after 24 hours. Between 4.00 and 8.00 hours, the Theophylline plasma levels were particularly high, so that in this biorhythmically critical period, the therapeutic effect of Theophylline following an evening single dose of Uniphyllin, is optimally developed.

Adult↗
PubMed1984

[Treatment of chronic obstructive respiratory disease with a new purified theophylline preparation in delayed-action form].

The treatment of chronic obstructive respiratory diseases with sustained release theophylline is steadily gaining in importance. Body plethysmography is applied for evaluating the extent of bronchospasmolysis during therapy of a new sustained release formula. A traditional prolonged-action theophylline-ethylenediamine preparation was administered to obtain comparative data. The sustained release formula containing pure theophylline meets the standards of a modern theophylline therapy. The graduation of the film tablet allows individualized dosage without losing the sustained release action by slowly increasing the theophylline-serum-level during a dosage interval of 12 hours.

Aged↗
PubMed1983

Time course of the bronchial response to salbutamol after placebo, betaxolol and propranolol.

The effects on specific airway conductance (sGaw) of placebo, betaxolol and propranolol following the inhalation of salbutamol were studied in 8 healthy volunteers by whole body plethysmography. Each subject received placebo and single oral doses of betaxolol 40 mg and 80 mg, and propranolol 160 mg, and 320 mg. sGaw was measured before dosing and after 2 h, just before salbutamol was inhaled. It was then measured again after 15 min and 0.5, 1, 2, 3, 4 and 6 h. sGaw 2 h after the beta-blockers did not differ from the value whilst on placebo. The peak response to salbutamol after placebo and both doses of betaxolol was almost identical, whereas it was significantly reduced after propranolol. The AUC of the response to salbutamol over 6 h showed a reduction of 11% after betaxolol and of 19% after propranolol (p less than 0.01 between beta-blockers). The results indicate that, after betaxolol and in contrast to propranolol, a proportion of the bronchial beta 2-receptor population remains available to a beta 2-agonist.

Adrenergic beta-Antagonists↗
PubMed1981

Cardiovascular effects of diltiazem in healthy volunteers at rest, supine and erect, and during physical and mental stress.

The hemodynamic effects of diltiazem were investigated in six volunteers at rest, supine and erect, under psychologic stress and orthostatic conditions. Plasma concentrations were also estimated. Under all conditions diltiazem showed a vasodilating property that was more pronounced on the arterial resistance vessels than on the pulmonary vessels. The first plasma concentrations were detected 15 min after drug intake, and the highest values were seen at the end of the study in the 3rd h.

Adult↗
PubMed1980

[Clinical pharmacological trials of a new metered dose inhaler, IK-6, a combination of the bronchodilators fenoterol and ipratropium bromide (author's transl)].

IK-6, a combination of the sympathomimetic fenoterol (low dose) and the anticholinergic ipratropium bromide (normal dose), was tested single-blind and cross-over in outpatients with intrinsic asthma and in healthy volunteers. In 12 patients IK-6 resulted in a good acute bronchodilatation, the onset was as quick as following fenoterol and the maximum was as good as following ipratropium bromide. In another 12 patients the protective effect against an acetylcholine-induced bronchoconstriction was better after IK-6 than after ipratropium bromide and much better than after salbutamol. In these patients IK-6 caused no unwanted side effects. In 10 healthy volunteers the effect on heart rate was tested after inhalation of 20 puffs of bronchodilators applied by metered dose inhaler. The anticholinergics (ipratropium bromide, oxitropium bromide, dibenzothiepine-derivative) caused no effect. Following fenoterol a marked increase in heart rate could be observed, whereas the combination IK-6 caused only a slight increase.

Aerosols↗