Pharmacokinetics of isosorbide dinitrate and isosorbide-5-mononitrate

Abstract

Short-acting nitrates like glyceryl trinitrate are most suitable for interrupting attacks of angina pectoris, long-acting nitrates for their prophylaxis. A salient feature of drugs used in prophylaxis is a long duration of action. Among many organic nitrates developed for this purpose, ISDN became the most prominent. ISDN is metabolized to isosorbide-2-mononitrate (IS-2-MN) and isosorbide-5-mononitrate (IS-5-MN) which are pharmacologically active. Since denitration is practically the only way of elimination, the denitration rate of the compounds is proportional to their total body clearance, which is 3.2 l/min for ISDN, 0.371 l/min for IS-2-MN and 0.124 l/min for IS-5-MN. Their terminal elimination half-life is 63, 108 and 264 min respectively. These figures are the weighted means from studies with intravenous administration. Several authors determined the AUCs of ISDN and its mononitrates after administration of ISDN. From the AUCs and the respective total body clearances, the amounts of ISDN were calculated which enter the systemic circulation intact, and those of the mononitrates formed by denitration of ISDN. After intravenous administration of ISDN, 62% were metabolized to IS-5-MN, 24% to IS-2-MN. The remaining 14% must be eliminated by other routes. After oral administration as plain tablets, 26% of the ISDN enter the systemic circulation intact. Forty-seven percent of the dose are metabolized to IS-5-MN during absorption, 17% after absorption. The figures for IS-2-MN are 14% and 5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)