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

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 1...

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Bibliographic Details
Published in:European journal of clinical pharmacology 1994, Vol.46 (4), p.319-324
Main Authors: Vogt, D, Trenk, D, Bonn, R, Jähnchen, E
Format: Article
Language:English
Subjects:
Administration, Oral
Administration, Sublingual
Adult
Aerosols
Blood Pressure - drug effects
Cross-Over Studies
Double-Blind Method
Heart Rate - drug effects
Hemodynamics - drug effects
Humans
Isosorbide Dinitrate - administration & dosage
Isosorbide Dinitrate - blood
Isosorbide Dinitrate - pharmacokinetics
Isosorbide Dinitrate - pharmacology
Male
Tablets
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Summary:The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers. After the sublingual spray Cmax was higher (39.0 ng.ml-1) and tmax was shorter (3.9 min) than after the sublingual (22.8 ng.ml-1 and 13.8 min) and peroral (16.9 ng.ml-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng.ml-1.min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively. The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions.
ISSN:0031-6970
1432-1041
DOI:10.1007/BF00194399