Variations in the clearance of isosorbide dinitrate and its two active metabolites according to the nature of the membrane in simulated dialysis

Abstract

Many dialysis patients with chronic terminal renal failure also suffer from cardiovascular conditions such as angina pectoris, for which they are treated with isosorbide dinitrate (ISDN). It is now accepted that nitrates can interact with many plastics and other biomaterials, but no work has been published on dialysis membranes. Accordingly, we studied the influence of dialysis, and in particular the influence of the nature of the membrane on the plasma concentration and the elimination of ISDN and its two active metabolites, isosorbide 2- and 5-mononitrates (2- and 5-ISMN). We simulated dialysis in vitro, to study the influence of seven different membranes on the levels of these nitrates. The concentrations of the three nitrates were measured upstream and downstream of the membrane (A and B, respectively), and in the ultrafiltrate (C), at times 5, 15, 30, 45 and 60′. Significant differences in concentration were found for ISDN in the three sample solutions A, B and C against time with the polysulfone, polyacrylonitrile, cellulose acetate and cellulose triacetate. These differences are apparently due to an interaction of ISDN with these membranes. In addition, significant differences in ISDN concentrations were observed between the polysulfone membrane and the polyacrylonitrile, hemophan and cuprophan membranes. However, these differences diminished with time and were no longer significant after 1 h. There was no significant difference in 2- and 5-ISMN concentrations in time between any of the sample solutions that could be attributed to metabolite-membrane interactions, or between different membranes.