Acetohexamide and Tolbutamide Effects in Non-Diabetic and Diabetic Adults.

Abstract

The studies herein described indicate that in healthy subjects the hypoglycemic effect of intravenous sodium acetohexamide (N-pacetylphenylsul fonyl-N'-cyclohexylurea) is, on a weight basis, as great as that of sodium to1 bu tamide( 1 -bu tyl-3 -p-to1 ylsulf onylurea ) but lasts longer. In patients with diabetes mellitus the two drugs administered intravenously appear to be of about equal potency in this respect, though in some the responses may be somewhat greater with the one or the other drug.Materials and methods. One gram of sodium acetohexamide (2.5% solution in water with added sodium mono-and dibasic phosphate, sodium hydroxide, and phenol) or 1 .O g sodium tolbutamide (5% solution in water) was administered intravenously in the fasting state during a 3-minute interval to non-diabetic adults (14 prisoners, 1 adult with muscular dystrophy, and another adult suspected of diabetes mellitus but found to have a non-diabetic glucose tolerance) and to 6 patients with diabetes mellitus not under treatment with insulin or an oral hypoglycemic agent. Venous blood was withdrawn for blood sugar and serum inorganic phosphorus analyses prior to the injection and at 15-or 30-minute intervals thereafter for a total of 2 hours. The ability to dispose of a glucose load was used as an index of the presence of a non-diabetic or a diabetic state: 1.75 g/kg of body weight were ingested orally as a 50% solution in water and levels of blood sugar measured in the fasting state and during the succeeding 5-hour interval. In the non-diabetic group the 2 hour glucose tolerance blood sugar values ranged between 61 and 85, and in the diabetic group, between 211 and 584 mg%.Results. The data in Table I indicate that the mean hypoglycemic responses of 16 nondiabetic adults to sodium acetohexamide and to sodium tolbutamide were of the same order of magnitude during the first 45 minutes (Table I). However, the hypoglycemic effect of sodium acetohexamide was more prolonged, as indicated by the significantly lower mean blood sugar values a t the 60, 90, and 120 minute points.In these adults without diabetes mellitus, the decrease in serum inorganic phosphorus after acetohexamide, an indirect index of carbohydrate metabolism( 1 ) , was no greater than that following tolbutamide, if the evaluation is based on changes from the mean concentration present at zero time (Table 11).It is to be noted, however, that the solution of acetohexamide contained phosphate buffer (79 mg percent of inorganic phosphorus by actual measurement). Hence the injection of 40 ml of the acetohexamide solution might be expected to raise the concentration of inorganic phosphorus by approximately 0.22 mg%, assuming that the inorganic phosphorus was distributed only within the extracellular fluid. In view of this the changes in serum inorganic phosphorus following acetohexamide and tolbutamide have also been calculated with the 15 minute value as the reference point. These calculations reveal that, compared to tolbutamide, acetohexamide produced a greater degree of hypopho...

Prolonged Hypoglycemia Following Acetohexamide Administration: Report of Two Cases with Impaired Renal Function

“…Liver damage might exert its effect in these cases in two ways: (a) Decreased glycogen storage as seen in malnutrition 8 and cirrhosis 7 could be expected to set the stage for hypoglycemia following the administration of sulfonylureas. 10 The plasma of the first case contained 50 ^g./ioo ml. Furthermore, Case 1 reported here as well as several others in the literature have all shown at least as good a response to treatment with glucagon, which acts to release glucose from stored liver glycogen, as with glucose infusions.…”

Comparison of Acetohexamide with Other Sulfonylurea Compounds in the Treatment of Diabetes Mellitus

“…This is in accordance with other clinical observations (3, 16,17,19). It has been claimed, however, that patients who fail to react to one sulfouylurea drug do occasionally respond to another generally less potent hypoglycemic agent (5) and also chlorpropamide failures have thus been reported to respond to acetohexamide (3). Although chlorpropamide undoubtedly is usually a more potent hypoglycemic agent serious toxic manifestations, such a s cholestatic jaundice (20) are occasionally encountered with its use and chlorpropamide is for this reason regdrded by many authors to be definitely more toxic than tolbutamide, which seldom causes any complications of th's kind.…”

“…I t has been pointed out, however, that abnormalities of liver function in diabetic patients must be interpreted with caution since abnormal tests are frequently encountered in diabetics who have not been on any oral drugs (14). I t has already been mentioned, that the duration of action of acetohexamide is longer than that of tolbutamide (5,15) and acetohexamide can therefore be used in one daily dose in contrast to the latter drug, which must be administered in divided dosage. The duration of the hypoglycemic effect produced by acetohexamide seems to be intermediate between that of tolbutamide and chlorpropamide but the duration of action is nevertheless considerably shorter than with the use of the latter drug, which has been reported to have a half life of 36 hours in body fluids in its active form and a duration of action extending up to 60 hours (8,13).…”