- The Japanese Society of Clinical Pharmacology and Therapeutics
- Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics (ISSN:03881601)
- vol.13, no.3, pp.463-475, 1982-09-30 (Released:2010-06-28)
A transdermal sustained release formulation. of isosorbide dinitrate (Frandol Tape) has been developed for the purpose of prolonging the preventive effect of isosorbide dinitrate (ISDN) against attacks of angina pectoris.The plasma levels of ISDN and the two metabolites, isosorbide 2-mononitrate and isosorbide 5-mononitrate, were measured after the application of Frandol Tape (ISDN 40mg) in ten healthy male volunteers. After a single application of the tape to the breast for 24 or 48 hrs, the mean plasma levels of ISDN increased slowly to reach their peaks of 2.6 or 2.7 ng/ml at 6 hrs and declined very slowly to 1.9 ng/ml at 24 hrs or to 1.4 ng/ml at 48 hrs after the application. After removal of the tape, the mean plasma levels of ISDN declined with a half-life of 2.3 hrs.The area under the plasma level versus time curve (AUC) for ISDN per the amount of ISDN absorbed percutaneously after a transdermal administration was larger than after an oral administration. Probably because ISDN was not susceptible to“first-pass effect” in the cutaneous route. On the other hand, it was suggested that urinary excretion behavior after a transdermal administration was similar to that after an oral administration.These results demonstrated that Frandol Tape might be an useful transdermal sustained release formulation of ISDN for the prevention of angina pectoris, since the plasma level of ISDN is maintained constantly during the period of application.