[Evaluation of pharmacodynamic equivalence of glycerol trinitrate-containing sprays for oral administration with or without chlorofluorocarbons ].
Evaluation of Pharmacodynamic Equivalence of Glyceryl Trinitrate Sprays for Oral Application with or without Fluorochlorohydrocarbons. The pharmacodynamic equivalence of a fluorochlorohydrocarbons(FCH)-free vs a FCH-containing glyceryl trinitrate (NTG, CAS 55-63-0) spray was investigated. Three oral sprays were administered at 24 h intervals to 9 male and 6 female healthy subjects in a double-blind placebo-controlled period-balanced 3-way cross-over study design: treatment NT (FCH-free, NTG-containing spray, dose of 0.8 mg NTG), treatment NR (FCH- and NTG-containing spray, dose of 0.8 mg NTG) and treatment PL (placebo: FCH- and NTG-free spray, dose of 2 puffs). The treatments were administered after suitable preparation and under strict standardisation. Subsequently digital plethysmography (systolic a-wave, dicrotic b-wave and the c-incisura) was monitored for 2 h. After administration of the NTG-containing sprays (NR and NT) the median a-wave increased rapidly, the median c-incisura deepened and the median b-wave rose slightly. The time courses of these changes and those of the resulting b/a- and c/a-ratios were superimposable and clearly distinct from those after PL. On the basis of the analysis of variance of the response variables (Rmin: maximum drop, and A(0-60): the area under the time course during the first hour after dosing) of the c/a-ratio as change from the predosing baseline, the following point estimates and 90% confidence intervals (CI) were calculated for the true ratio of treatments NT/NR: 104.4%, CI: 88.3 to 120.5% for Rmin, and 101.4%, CI: 79.3 to 123.5% for A(0-60).(ABSTRACT TRUNCATED AT 250 WORDS)
Erb
K A
KA
Zentrum für Kardiovaskuläre Pharmakologie, Mainz.
de Mey
C
C
Wolf
G K
GK
Kroll
M
M
Belz
G G
GG
D000280:Administration, Inhalation; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D005617:Chlorofluorocarbons, Methane; D005260:Female; D005385:Fingers / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects
D005617:Chlorofluorocarbons, Methane; D005996:Nitroglycerin
Prüfung der pharmakodynamischen Aquivalenz von Glyceroltrinitrat-haltigen Sprays zur oralen Anwendung mit und ohne Fluor-Chlor-Kohlenwasserstoffe.