Twenty-nine cases of hypoglycemia induced by disopyramide (DP) have been reported in the literature to date. Twenty of the reported cases showed hypo-renal function and a high concentration was rare. DP is metabolized to mono-N-dealkyldisopyramide (MND) in the liver and accumulation of MND is to be expected in renal failure. Both DP and MND bind mainly to alpha-l-acid glycoprotein (AAG) in the plasma. In 10 hemodialysis (HD) patients with normal liver function receiving DP therapy in the steady state. DP, MND and AAG were measured pre- and post-HD. Ten patients with normal renal and liver function were selected as the controls. The DP concentration was 2.08±0.39μg/ml (mean±SD) in the control group, and the pre-and post-HD levels were 2.40±1.08μg/ml and 1.73±0.87μg/ml, respectively, in the HD group. The MND concentration was 0.42±0.23μEg/ml in the controls, 1.53μ 0.52μg/ml in pre-HD and 1.08±0.32μg/ml in post-HD. Although DP and MND are both classified as substances of small molecular weight, the average decrease in plasma concentration from pre- to post-HD was under 30% with both agents. The MND/DP ratio in the HD group was higher than in the controls, but there was no significant difference between pre and post-HD. The AAG level was 75±5mg/dl in the controls and 109±11mg/dl before HD in the HD group (P<0.001). In conclusion, MND accumulation was observed in the HD patients receiving DP therapy. Since the anticholinergic effect of MND is 24 times that of DP, MND is thought to contribute in some way to the hypoglycemia induced by DP in renal failure.
