PHARMACOKINETICS OF ORAL GLYBURIDE IN SUBJECTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS AND RENAL-FAILURE

To test the hypothesis that renal failure has no effect on the pharmac okinetics of glyburide, five subjects with non-insulin-dependent diabe tes mellitus (NIDDM) and end-stage renal disease requiring hemodialysi s, and four NIDDM subjects with normal renal function were studied. On days 0, 1, and 15, subjects consumed 33 carbohydrate grams, and gluco se, insulin, and C-peptide were measured for 4 hours. On day 1, subjec ts received 3 mg glyburide and measured plasma concentrations for 48 h ours. On day 3, multiple dosing on 3 mg glyburide daily began. On day 15, plasma concentrations were measured for 48 hours. The pharmacokine tics and pharmacodynamics of glyburide, glucose, insulin, and C-peptid e were determined as well as daily fasting blood glucose. Glucose area under the curve (AUG) and daily fasting glucose levels did not change in either controls or hemodialysis subjects. The mean serum glyburide blood levels and pharmacokinetics did not differ after initial or chr onic glyburide administration in NIDDM subjects with end-stage renal d isease treated with hemodialysis compared with controls. Glyburide hal f-life averaged 3.3 hours in control subjects and 5.0 hours in hemodia lysis subjects. Hemodialysis subjects had increased C-peptide and insu lin AUC with chronic dosing. Renal failure does not affect the pharmac okinetics of 3.0 mg oral glyburide. (C) 1997 by the National Kidney Fo undation, Inc.