[Pharmacokinetics and pharmacodynamics of a new 80 mg oral delayed-action isosorbide dinitrate preparation]

A new galenic form of isosorbide dinitrate (consisting of a hydrophilic matrix which allows very slow release of the active drug) was studied from the pharmacokinetic and pharmacodynamic view points in 11 patients with stable angina pectoris under betablocker therapy. After testing their sensitivity to nitrates with a sublingual trinitrin test causing a fall greater than or equal to 20 mmHg in systolic and greater than or equal to 10 mmHg in diastolic blood pressure, the patients were given a single tablet of Risordan LP 80 daily for 7 days. The equilibrium plasma concentrations of isosorbide dinitrate and its mononitrate metabolites (2-isosorbide mononitrate and 5-isosorbide mononitrate) over 24 hours were measured on the 6th treatment day. A method of measuring these nitrate derivatives has been developed and validated. The concentrations measured enabled the study of the pharmacokinetics of this new form, showing an average minimal concentration of 5-isosorbide mononitrate (principal metabolite) of 85 +/- 41 micrograms/l and an amplitude of fluctuation over the 24 hours period of 296 +/- 102 micrograms/l. From the pharmacodynamic point of view, the evaluation of the sensitivity to a single dose of 0.75 mg of trinitrin 24 hours after the first dose of Risordan LP 80, just before the second dose and 24 hours after the seventh dose, showed a significant difference (average decrease of 40 +/- 19 mmHg in systolic blood pressure) with respect to the values observed during the selection phase.(ABSTRACT TRUNCATED AT 250 WORDS)