[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)
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Zentrum für Kardiovaskuläre Pharmakologie ZeKaPha GmbHa, Mainz/Wiesbaden.
de Mey
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Zimmermann
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Mutschler
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Roll
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Belz
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GG
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.