Carbohydrate Metabolism in Uremia: Blood Glucose Response to Sulfonylurea

Clinical Pharmacokinetics of Sulphonylurea Hypoglycaemic Drugs

“…Acetohexamide ( fig. la) is eliminated from the body by its parallel biotransformation into an inactive and an active hydroxylated metabolite (Cohen et al, 1967). The apparent half-life of elimination of acetohexamide is about 1.3 hours in normal subjects, and that of its active metabolite, hydroxyhexamide, about 6 hours.…”

“…The concentration of hydroxyhexamide, the active metabolite which also shows uricosuric properties, is only moderately elevated in some uraemic patients and not elevated in others, owing to further biotransformation to pharmacologically inactive dihydroxyhexamide (Cohen et al, 1967). The precise clinical consequences of this behaviour have not been elucidated, but episodes of severe hypoglycaemia have been observed as a result of impairment of the second biotransformation or impairment of renal excretion of hydroxyhexamide (Alexander, 1966).…”

Clinical Pharmacology of Sulfonylureas

“…Absorption depends on formulation (NASH et al 1977). A distribution volume of 0.2l!kg can be estimated from published data (SMITH et al 1965;COHEN et al 1967). Acetohexamide is highly protein bound at about 90%, the main component at approximate\y 80% being albumin (JUDIS 1972;Hsu et al 1974).…”

“…A prolonged half-life of acetohexamide has been reported in renal disease, but more important is probably the reduction of the renal elimination of the active metabolite (COHEN et al 1967), although this can be further converted to dihydroxyhexamide.…”

Spontaneous Hypoglycemia Associated with Chronic Renal Failure

“…9 " 11 Episodes of severe and prolonged hypoglycemia in diabetic, uremic patients on insulin or oral hypoglycemic agents have also been reported. 12 Recently, spontaneous hypoglycemia was documented in three diabetic patients in renal failure who were being managed by diet alone 7 and in one nondiabetic with a comparable level of renal insufficiency. 8 The latter case is, to our knowledge, the first report of hypoglycemia occurring with renal insufficiency in the absence of diabetes.…”