Changes in Plasma Concentrations after Application of Isosorbide Dinitrate Tape in A-C Bypass Surgical Patients

The pharmacokinetics of a tape formulation of isosorbide dinitrate (ISDN) was investigated in aorto-coronary bypass (A-Cbypass) surgical patients. Transdermal sustained-release dosage forms of ISDN (Frandol Tape®) were applied to 6 patients (ages42 to 68 yr) with angina pectoris, prior to A-C bypass surgery. The plasma ISDN concentrations and urinary volume of these patients were evaluated before, during, and after cardiac operation.The mean plasma ISDN concentrations fell from6.5ng/ml at the start of the extracorporeal circulation (ECC) to4.7ng/ml and 4.1ng/ml after 15 and 60min of ECC, respectively. Two hr after the end of ECC, however, the mean plasma concentrations of ISDN had risen to 6.8ng/ml. The forecast of plasma ISDN concentrations after 2 and 6hr were estimated from the end of ECC by using the population pharmacokinetic analysis.The calculated concentrations of ISDN were successfully fitted to the observed plasrna data. The mean rate of urine flow showed significant correlation with percentage change in plasma ISDN concentration (P<0.05).From these results, it is concluded that application of ISDN tape before A-Cbypass operation may be useful for drug treatment.