Studies of the bioavailability of nitroglycerin from a transdermal therapeutic system (Nitroderm TTS)

Abstract

In 6 healthy volunteers, intravenous infusions of nitroglycerin 4.8 and 10.6 micrograms/min yielded mean steady-state plasma concentrations of 0.5 +/- 0.02 and 0.82 +/- 0.04 ng/ml as determined by a gas chromatographic/mass spectrometric method. The plasma concentrations reached in the same subjects 17 h after application of Nitroderm TTS 5 and 10 with in vivo release rates of 3.7 and 5.7 micrograms/min were 0.28 +/- 0.01 and 0.37 +/- 0.01 ng/ml, respectively. Thus, 75% of the quantity of nitroglycerin released by the systems passed into the circulation. The inter-individual and intra-individual variations in plasma concentrations were similar for both modes of administration. The nitroglycerin-induced morphological changes in the fingerpulse wave were clearly dose-dependent, but it seems that this pharmacodynamic parameter is determined less by the plasma concentration than by the nitroglycerin content of the vascular wall.

Nitric Oxide Is Released Into Circulation With Whole-Body, Periodic Acceleration * *Dr. Sackner is Chief Executive Officer and Chairman Board of Directors, Non-Invasive Monitoring Systems, Inc., and owns approximately 37% of Non-Invasive Monitoring Systems, Inc. shares. He is also a member of the Board of Directors, Vivometrics, Inc., Ventura CA. Ms. Gummels owns approximately 0.2% of Non-Invasive Monitoring Systems shares. Dr. Adams is a member of the Scientific Advisory Board and owns approximately 0.1%

“…With either ratio, a dose response to NO donor drugs has been observed. 17,24 In terms of peak response of the a/b ratio, wholebody, periodic acceleration produces far higher values than organic nitrate preparations that release NO or albuterol and terbulaline that act through a NO pathway. The peak a/b ratio in the current study increased 2,200% in healthy adults and 3,775% from baseline in the patients with inflammatory diseases.…”

Hemodynamic Effects of Nitroglycerin Ointment in Emergency Department Patients

“…16 Nitroglycerin infusions at 5 mcg/min and 10 mcg/min produce lower steady-state plasma concentrations of 0.5 ng/ml and 0.8 ng/ml, respectively. 17 We performed impedance cardiography at time points up to 120 minutes based on nitroglycerin's pharmacokinetic profile 11,16 ; however, the peak effect of nitroglycerin may be achieved later in some patients.…”

Digital pulse plethysmography (DPG) in studies of the hemodynamic response to nitrates — A survey of recording methods and principles of analysis

“…Another form of electronic pneumoplethysmography for DPG is an air dfferelrtial transducer sysiem used in the nitrate studies performed by Porchet & Bircher (1981 and by Muller et al (1984).…”

“…This procedure does not catch in detail the special features of dicrotism which should more correctly be expressed numerically by use of other measures applicable manually at the laboratory desk to single pulse waves, or automatically obtained by computer processing. Imhof et al (1980Imhof et al ( , 1981Imhof et al ( , 1982Imhof et al ( , 1984 and Muller et al (1984) studied the effect duration of various nitrate preparations. As expression of nitrate dilatation they used the relative amplitude of the dicrotic wave, obtained by dividing the height of the systolic peak with the height of the dicrotic notch from the base-line of the pulse wave.…”

“…As Imhof et al (1984) found very long-lasting hemodynamic effects with Transiderm-Nitro patches we made a few experiments of the same kind using Transiderm-Nitro 10 mgl24 h with our E J 3 2 y r l F B e l a r e and A l t e r 0 2 5 m g N T G Sublinyaily set-up. We were able to record a duration of effect for at least eight hours and probably longer.…”