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Biomedical subjects

B Spilker

Publications and source records attributed to B Spilker.

At least 37 records · Page 2Linked to original sources
PubMed1983

Practical considerations in planning and conducting clinical trials with investigational or marketed drugs.

A system is presented to increase efficiency in planning, initiating, conducting, and analyzing the results of a clinical trial. The procedures to be used are designed to assist clinical investigators of sponsored or unsponsored studies, as well as drug corporations and other sponsors of drug studies. The series of checklists and steps to follow may be easily modified for individual trials. The procedures and steps to be implemented are described in terms of the following nine categories: Interview and Selection of Investigator(s); Clinical Study Initiation: I. Internal Documents and Procedures; Clinical Study Initiation: II. Information for the Investigator to Send to the Sponsor; Clinical Study Initiation: III. Information for the Sponsor to Send to the Investigator; Prestudy Roundtable Meeting; Conducting the Clinical Study; Monitoring and Troubleshooting a Study; Clinical Study Termination; and Clinical Study Data Entry and Analysis.

Clinical Trials as Topic↗
PubMed1978

Medication records.

Explore the source record for details and available documents.

Drug Interactions↗
PubMed1976

On the question of tachyphylaxis to isoproterenol in guinea pigs.

Isoproterenol (4 mug/kg, i.m.) decreased mortality of conscious guinea pigs to histamine, when histamine was injected 8 min after a single dose. But, when guinea pigs were injected with isoproterenol or saline every 20 min for 5 hr, followed by a histamine challenge 8 (or 120) min later, there was no difference in mortality between the two groups. This failure of repeated doses of isoproterenol to protect guinea pigs (from effects of histamine) may be related to its cardiovascular effects, since control blood pressure decreased significantly more in the isoproterenol group than in the saline group. This hypothesis was supported by the observation that histamine-induced mortality was significantly increased in guinea pigs treated with a vasodilator (minoxidil), whose blood pressure decreased to the same level (54 +/- 5 mm Hg) as that observed after repeated doses of isoproterenol. Tachyphylaxis to heart rate or blood pressure responses of isoproterenol was not observed. 10 repeated additions of isoproterenol to spontaneously beating atria or tracheal strips did not show any tachyphylaxis, nor did 15-20 additions of isoproterenol to perfused lungs.

Animals↗
PubMed1975

Cardiovascular effects and blood concentrations of ajmaline and its 17-monochloroacetate ester in cats.

The antiarrhythmic drugs ajmaline and its 17-monochloroacetate ester (MCAA; Rtimos-Elle) were studied in cats. MCAA was less than half as toxic as ajmaline. Non-lethal doses of MCAA decreased blood pressure before heart rate, whereas ajmaline initially decreased heart rate. Both drugs prolonged the PR, QRS and QT intervals of the EKG. Recovery of these effects was within one hr. MCAA (10 mg/kg) and ajmaline (4.05 mg/kg) were studied separately by a one and 10 min infusion in the same cat. The dose of MCAA was ten times the usual dose in man and that of ajmaline four times the usual clinical dose. More marked effects were observed with the one min infusion. Arrhythmias were usually observed with ajmaline, but not with MCAA, even though it was rapidly converted to ajmaline. Maximal cardiovascular effects of MCAA and ajmaline were observed within 3 min of the end of infusion, which was also the time of peak blood levels. The elimination of MCAA resembled the kinetics of a multi-compartment system after a one min infusion. Peak blood levels declined by one-half in 3 min. Ajmaline blood levels declined linearly, with a half-life of 100 min, after a one min infusion. The peak blood level of MCAA after an intraduodenal dose of 25 mg/kg occurred at 20 min, whereas the peak blood level of the ajmaline formed occurred at 4 hr. In conclusion, MCAA has some different pharmacological properties and different kinetics of elimination than ajmaline.

Acetates↗
PubMed1975

Comparison of animal models for predicting bronchodilator efficacy in man.

In vitro and in vivo models of bronchodilation were compared to assess their relative usefulness for predicting clinical efficacy. Drugs studied were isoproterenol, isoetharine, salbutamol, hexoprenaline, terbutaline, ephedrine and aminophylline. In vitro preparations were guinea pig perfused lung, tracheal strip and spontaneously beating right atria. In vivo, drugs were compared by three routes in conscious guinea pigs and anesthetized dogs and relative potency estimates and separations of bronchodilator and heart rate effects of these agents were determined. The Spearman rank correlation coefficient was statistically significant when the effects of the drugs were compared for guinea pig perfused lung and tracheal responses, in vivo guinea pig and dog intravenous and oral (or intraduodenal) responses. Aerosol results did not correlate, most likely due to differences in experimental techniques. Relative potency estimates were in general agreement with human data in the literature and support the use of these tests for the study of bronchodilator agents.

Administration, Oral↗
PubMed1975

The role of bronchoconstrictors in evaluating smooth muscle relaxant activity.

Several bronchoconstrictor and smooth muscle relaxant agents were studied in a dog preparation (in vivo) and on guinea pig tracheal strips (in vitro). Isoproterenol, isoetharine and N-t-butylnorepinephrine, individually, had similar dose-response curves and ED50 values when tested as antagonists of histamine and carbamylcholine-induced bronchoconstriction in dogs. Diphenhydramine, cyproheptadine, thenyldiamine, atropine and suloxifen each exhibited more selective antagonism. A ratio of anticholinergic and antihistamine ED50s was obtained in dogs and on guinea pig tracheal strips. The rank order correlation coefficient of this ratio for each drug in the two species (rs = 0.93) was highly significant. Dose-responses to smooth muscle relaxant effects of isoproterenol were obtained with several different constrictors and experimental conditions on guinea pig tracheal strips. The choice of a constrictor and experimental conditions was found to affect EC50 values. The influence of resting tension, temperature, season, dibenamine-pretreatment and manner of performing the dose-response was evaluated. Both Ba and carbamylcholine were found to be suitable constricting agents under various conditions, whereas histamine, serotonin, potassium and rubidium had more limitations and eight other inorganic ions were not suitable.

Aerosols↗
PubMed1970

Comparison of the inotropic response to glucagon, ouabain and noradrenaline.

1. The inotropic activity of glucagon was compared with catecholamines and cardiac glycosides by in vitro procedures which were able to differentiate between the activities of the latter two groups.2. The frequency-force curve for glucagon resembled that of noradrenaline at low stimulation frequencies (1 and 2/min) and that of ouabain at more rapid frequencies of stimulation.3. Noradrenaline and adrenaline increased the amplitude of contraction of cat papillary muscles and markedly shortened the time to reach peak tension. Ouabain and glucagon increased tension without any change in the time to peak tension.4. Noradrenaline caused a rapid onset and rate of rise of contraction of cat aortic strips, whereas the response to ouabain was slow in onset and rate of development. Glucagon had no effect on this preparation, even at high concentrations.5. Manganese ions caused a shift of the dose-response curve to ouabain and glucagon, but not to noradrenaline or calcium. In 0.5 mM Ca media, the response to ouabain was abolished and the curve to noradrenaline shifted.6. When glucagon was added to an atrial preparation, the time to the initial increase in tension and the time to maximal tension was intermediate between that necessary for noradrenaline and that necessary for cardiac glycosides.7. Propranolol blocked the inotropic response to noradrenaline, but not to either ouabain or glucagon.8. A relative measure of contraction-dependency was described. Cardiac glycosides exhibited a greater degree of contraction-dependency than either noradrenaline or glucagon.9. Adrenaline elevated the depressed plateau of the action potential from calf and sheep Purkinje fibres, but ouabain and glucagon were without effect.10. Electrophysiological measurements demonstrated that moderate concentrations of glucagon exerted only a small effect in prolonging atrial and ventricular action potentials.11. Several pharmacological blocking drugs and other inotropic agents did not potentiate or block the inotropic response to glucagon. Reserpine pretreatment increased the response to glucagon.12. It was concluded that glucagon has its own spectrum of inotropic activity and does not completely mimic the effects of either ouabain or noradrenaline.

Action Potentials↗