Relationship between pharmacokinetics and hemodynamic tolerance to isosorbide-5-mononitrate

Abstract

Healthy male volunteers received three different dose regimens of a controlled-release form of isosorbide-5-mononitrate (IS-5-MN; 60 mg per tablet). Dose regimen I consisted of a single daily dose of 60 mg given for 5 days. Dose regimen II was started with a dose of 60 mg, followed by 30 mg 12 h later and thereafter every 8 h. The last dose, on the 5th day was again 60 mg. In dose regimen III 60 mg followed by 30 mg 6 h later were administered every day for 5 days. The peripheral arterial and venous effects of IS-5-MN during the first and last dosing interval were followed by changes in the finger pulse curve, standing systolic blood pressure, heart rate, and venous distensibility. Plasma concentrations of IS-5-MN were measured frequently following the first and the last dose. Following dose regimen I all hemodynamic effects produced by the first dose were maintained during the study. The maximal plasma concentrations were about 400 ng/ml and the trough value, lower than 100 ng/ml. Following dose regimen II the hemodynamic effects of IS-5-MN and sublingual glyceroltrinitrate were completely abolished on the 5th day. Trough plasma concentrations were approximately 300 ng/ml during the entire study period. Following dose regimen III pronounced hemodynamic effects were seen on the 1st day. However, a significant attenuation of the hemodynamic effects was measured on the 5th day, when trough plasma concentrations were between 100 and 230 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular Effects of Auricular Acupuncture Evaluated via Two Digital Volume Pulse Measurements

“…Photoplethysmography provides a simple means of deriving the DVP. Several studies have revised the usefulness of the reflection and stiffness indices to assess and quantify effects of vasoactive drugs and nitrates in systemic haemodynamics, such as changes in heart rate and blood pressure (Wagner et al, 1990;Millaseau et al, 2006). To the best of our knowledge, RI DVP and SI DVP have not been previously used to study the vascular mechanisms of auricular acupoints.…”

A new isosorbide dinitrate extended-release formulation: pharmacokinetic and clinical parameters in patients with stable angina pectoris

“…Digital plethysmography, with measurements of changes in the relative height of the dicrotic notch, has been used in several previous nitrate studies [13][14][15] often as a substitute for clinical effects. In the present study, a close relationship was demonstrated between this parameter and ISDN plasma concentrations at 1 h. However, in this small sample the changes observed with plethysmography were not significantly related (across individuals) to the effects on exercise performances, blood pressure or heart rate.…”

Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

“…The digital pulse throughout the study was recorded at the same distal phalanx using a photo electric sensor (Hellige AG, Freiburg, FRG), and the signal was amplified by an ECG-recorder (Hellige Cardiognost EK 413, Hellige AG, Freiburg, Germany). At least 20 pulse waves were recorded during each measurement and the a/b ratio was calculated, where a is the height of the systolic peak and b the high of the dicrotic wave (Imhof et al 1980;Wagner et al 1990;Wiegand 1991;1992). Ten consecutive waves were evaluated and the a/b ratios were averaged.…”