Pharmacodynamic equivalence and clinical trial of a new fluorocarbon-free glycerol trinitrate pump spray with low ethanol content in comparison to a fluorocarbon-containing reference spray and a fluorocarbon-free pump spray with high ethanol content
Erb, K.; de Mey, C.; Zimmermann, T.; Mutschler, H.; Roll, S.; Belz, G.G.
Arzneimittel-Forschung 44(4): 478-482
1994
ISSN/ISBN: 0004-4172 PMID: 8011000 Document Number: 436769
The pharmacodynamic equivalence of a fluorohydrocarbons-(FCH)-free glyceryl trinitrate (GTN, CAS 55-63-0)-containing pump spray with low ethanol content (Nitrolingual-Spray N; TL) versus a conventional FCH-containing GTN spray (Nitrolingual-Spray, R) as reference and a FCH-free GTN pump spray with high ethanol content (TH) was investigated by digital plethysmography (DPG) in a double-blinded, placebo-controlled (TL-matched placebo spray), randomized, period-balanced, 4-way cross-over design. Additionally the clinical tolerability (as perceived by the subjects and reported to the treatments-administrating investigator) was determined. The DPG-changes (cla; ratio of c-incisure and systolic a-wave) after the sublingual (s.l.) administration of 0.8 mg GTN of TL were biostatistically equivalent with R: the confidence intervals (CI) of the point estimates of the maximal decrease in cla (TL/R: 0.98, 90%-CI: 0.84 to 1.14) and the area-weighted average decrease in cla (TL/R: 0.97, 90%-CI: 0.80-1.16) were well in a 80-125% tolerance range. The time of occurrence of the maximal DPG-effect of TL was not different from R (distribution-free estimate of the difference TL-R: -2.25 min, 95%-CI: -9.5 min to 2 min). In contrast the maximal DPG-effect of TH after the s.l. administration of 0.8 mg GTN had a statistically significant earlier onset (TH-R: -6 min, 95%-CI: -9.5 min to -2 min) and a higher area-weighted average response (TH/R: 1.12, 90%-CI: 0.95 to 1.34). TH consistently caused an utterly unpleasant burning sensation in the mouth, thus this perceived local discomfort was distinctly different compared to all other treatments.