Glycerol trinitrate (nitroglycerin) plasma concentrations achieved after application of transdermal therapeutic systems to healthy volunteers.

Glycerol trinitrate (nitroglycerin, in the following briefly called GTN) plasma concentrations achieved upon application of a commercial scale produced transdermal therapeutic system containing GTN (TTS-GTN, Nitroderm-TTS) were compared to those induced by 2 TTS-GTN prototypes previously used for clinical trials. Each system was applied to the chest, lateral aspect, of 14 healthy volunteers for 24 h, in a 3-period change-over study. GTN in plasma was determined by gas chromatography-mass spectrometry. The 3 systems released the drug continuously over 24 h. The mean plasma concentrations for all subjects and all sampling times (nmol/l) +/- SE were 0.92 +/- 0.18, 0.80 +/- 0.12 and 0.97 +/- 0.18 for the commercial scale TTS and the 2 other systems, respectively. No significant differences were demonstrated. The mean delivery rate of GTN calculated from the initial and residual contents of the TTS was 6.8 micrograms/min as a mean for the 3 systems. In another study, three different application sites were compared (chest, upper arm and pelvis). The results did not demonstrate significantly different GTN plasma levels. A comparison with published data after intravenous infusion showed a good availability of GTN administered transdermally by means of TTS. Its magnitude seems comparable to that of the intravenous route.