[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].
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Zentrum für Kardiovaskuläre Pharmakologie ZeKaPha GmbHa, Mainz/Wiesbaden.
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de Mey
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Zimmermann
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Mutschler
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D000286:Administration, Sublingual; D000328:Adult; D004311:Double-Blind Method; D000431:Ethanol; D005385:Fingers / Q000098:blood supply; D005466:Fluorocarbons; D006801:Humans; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D013810:Therapeutic Equivalency
D005466:Fluorocarbons; D000431:Ethanol; D005996:Nitroglycerin
Pharmakodynamische Aquivalenz und klinische Verträglichkeit eines neuen FCKW-freien Glyceroltrinitrat-Pumpsprays mit niedrigem Ethanol-Gehalt im Vergleich zu einem FCKW-haltigen Referenzspray und einem FCKW-freien Pumpspray mit höherem Ethanol-Gehalt.