ISSN:
1573-904X
Schlagwort(e):
nitroglycerin
;
transdermal administration
;
dose proportionality
;
dinitrate metabolites
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Chemie und Pharmazie
Notizen:
Abstract The FDA Cooperative Efficacy Study of transdermal nitroglycerin utilized a combination of marketed products over a wide dose range. Unfortunately, plasma nitroglycerin concentrations were not determined. The current study was conducted to assess plasma nitrate concentrations after transdermal doses of 15, 30, 60, and 105 mg/24 hr employing the FDA Cooperative Study design. Plasma concentrations of nitroglycerin, 1,3-glyceryl dinitrate, and 1,2-glyceryl dinitrate were determined during the 24 hr of application and for 1 hr after transdermal system removal. Dose proportionality was assessed after normalizing the data by theoretical dose. For nitroglycerin, dose-normalized AUC(0_∞) and C max were higher for the 105 mg/24 hr dose than for the other doses. For the metabolites, 1,3-glyceryl dinitrate and 1,2-glyceryl dinitrate, there were no differences in dose-normalized AUC(0_∞) and dose-normalized C max between the dose levels. No differences were seen in T max between the dose levels for all three species. Based on the dinitrate metabolites, dose proportionality was seen over the 15 to 105 mg/24 hr dose range. Nitroglycerin, however, was found to be linear only between 15 and 60 mg/24 hr.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1023/A:1015853200537
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