[Accumulation of a disopyramide metabolite in renal failure]

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-1-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 +/- 0.39 micrograms/ml (mean +/- SD) in the control group, and the pre- and post-HD levels were 2.40 +/- 1.08 micrograms/ml and 1.73 +/- 0.87 micrograms/ml, respectively, in the HD group. The MND concentration was 0.42 +/- 0.23 micrograms/ml in the controls, 1.53 +/- 0.52 micrograms/ml in pre-HD and 1.08 +/- 0.32 micrograms/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).(ABSTRACT TRUNCATED AT 250 WORDS)