[Hemodynamic effects of a transdermal formulation of isosorbide dinitrate and its pharmacokinetics in conscious dogs].
Transdermal application of isosorbide dinitrate (ISDN) in the form of a tape (ISDN-Tape) to conscious dogs, in a dose of 40 mg/dog, caused a slow decrease in pulse pressure. The maximum effect was obtained 12 hour after application. The pulse pressure was still under the initial level even after 48 hours of application. In contrast, a sustained-release tablet of ISDN (ISDN-SR-Tablet), given in a dose of 40 mg/dog, significantly decreased the pulse pressure of conscious dogs by reducing systolic pressure and slightly elevating diastolic pressure. The plasma concentrations of ISDN and its two metabolites, isosorbide 2-mononitrate (2-ISMN) and isosorbide 5-mononitrate (5-ISMN), were measured by gas chromatography after application of ISDN-Tape or ISDN-SR-Tablets. The time course pattern of the plasma concentration of ISDN after application of the both preparations ran quite parallel with their decreasing effect on the pulse pressure. After application of the ISDN-Tape, the plasma concentration of ISDN was maintained at a higher level than after the application of the ISDN-SR-Tablet. The maximum plasma concentrations of the two metabolites, however, were considerably lower in the case of the ISDN-Tape than in the case of the ISDN-SR-Tablet. These results were ascribed to the fact that ISDN given through the transdermal route, in contrast to that given by the peroral route, does not undergo the first-pass effect in the liver. It was concluded that the transdermal dosage form of ISDN, which possesses a more prolonged pharmacologic effect than the oral dosage form, may be useful in the prevention and cure of angina pectoris.
D000287:Administration, Topical; D000818:Animals; D003692:Delayed-Action Preparations; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007548:Isosorbide Dinitrate / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D007700:Kinetics; D012869:Skin Absorption
D003692:Delayed-Action Preparations; C030398:isosorbide-2-mononitrate; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate