Plasma Levels of Isosorbide Dinitrate and Its Metabolites during Intravenous Infusion in Surgical Patients

Six patients with ischemic heart disease were studied to determine plasma levels of isosorbide dinitrate (ISDN) and its metabolites, isosorbide-2-mononitrate (2-ISMN) and isosorbide-5-mononitrate (5-ISMN), using gas chromatography. These patients ranging in age from 43 to 80 years were administered intravenous isosorbide dinitrate at a rate of 1μg/kg/min during anesthesia and surgery. Surgery included gastrectomy, radical mastectomy and removal of lip tumor under either enflurane anesthesia or original neuroleptanesthesia. Plasma ISDN levels increased to 13.5±1.2 (mean±SE)ng/ml 30 min after the start of intravenous infusion of ISDN, and reached a plateau with the value of 28.1±5.2ng/ml 3hrs after the start of the infusion. Plasma 2-ISMN and 5-ISMN levels increased gradually up to 18.3±2.3ng/ml and 63.3±8.1ng/ml 4hrs after the start of intravenous infusion of ISDN, respectively. Plasma ISDN levels increased above the minimum effective plasma concentration (MEC) during intravenous infusion of ISDN. However, plasma 5-ISMN levels were below the MEC during the procedure. Pharmacological effect of intravenous ISDN was thought to depend on plasma concentration of ISDN.