Human pharmacological studies of a new transdermal system containing nitroglycerin

Abstract

A new transdermal therapeutic system (TTS) for the administration of nitroglycerin (NTG) was tested in human pharmacological studies in 26 healthy volunteers. Plasma concentrations and haemodynamic responses were determined after the application of the system in different dosages. The concentrations of NTG reached in the plasma were uniform and dose-related, i.e. dependent on the drug-release area, and showed only minor inter-individual variation. They remained almost constant as long as the system was in contact with the skin. Renewal of the system caused no appreciable change in the plasma concentration. The haemodynamic effects, like those of all nitrates, were not clearly related to the dose administered, and were not always dependent on the plasma concentration. Upon repeated application, NTG-TTS was well tolerated locally and systemically and led to no alteration in blood chemistry or haematological parameters. The typical nitrate headaches disappeared after a few days. The presence of the system on the skin caused no discomfort or inconvenience.

Influence of posture on plasma nitroglycerin [letter]

“…lafrate et al (1983) conducted studies of nitroglycerin ointment in the passive tilt configuration, and measured mean concentrations in the 9-30 ng/ml range. In both cases, these concentrations were in excess of those recorded by other workers with patients in experiments in which posture was not controlled, but which were certainly not conducted at 45 degree elevation or in the passive tilt position (Muller et al, 1982;Bashir et al, 1982).…”

Comparison of transdermal nitrate and isosorbide dinitrate in chronic stable angina.

“…The formulation of TN used in this study contains 25 mg of GTN in a patch of area 10 cm2. The diffusion rate is 20-40 ,ug h-1 cm-2, and so 5-10 mg of GTN would be released over a 24 h period, which produces a steady state plasma level of about 0.2 ng ml17 (Muller et al, 1982;Curry et al, 1984). In contrast, sublingual GTN 0.6 mg produces a peak plasma level of 2.3 + 0.36 ng ml71 at 2 min after drug administration (Armstrong et al, 1979).…”

“…The plasma concentrations of GTN observed after TN are dose-dependent, but the haemodynamic effects are not (Muller et al, 1982). It has proved difficult to establish a dose-response relationship for TN.…”

Efficacy and Rebound Phenomenon Related To Intermittent Nitroglycerin Therapy for the Prevention of Nitrate Tolerance

“…Moreover, the plasma renin activity and the plasma level of angiotensin II were increased during the application of the NTG tape. It has been known that the plasma level of NTG decreases rapidly after tape removal, and that the counterregulatory phenomenon persists for 4-6 h. 26 Therefore, the present results suggest that there is a balance between the nitrate effects (cGMP production) and the counterregulatory forces (the activation of neurohormonal factors) before tape removal during intermittent NTG therapy, and that the rapid decline in the plasma level of NTG after tape removal is accompanied by expression of these counterregulatory influences on vasodilation.…”