Effects of p-(di-N-propylsulfamyl) benzoic acid (benemid®) on free and total sulfonamide plasma levels

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exists between these two drugs as far as their ability to alter acute carditis. STUDIES OF FRUCTOSE METABOLISM IN INSULIN RESISTANT DIABETES. J. W. Craig, M.D.,* Max Miller, M.D., Hiram Woodward, Jr., M.D. * and W. R. Drucker, M.D.* (From the School of Medicine, Western Reserve Univ., Cleveland, 0.) Others have reported that fructose is utilized better than glucose by diabetic patients but that this advantage disappears after prolonged administration. This problem has been reinvestigated in a patient requiring 1,100 units of insulin daily. Insulin was withdrawn and 100 gm. of fructose were given intravenously each morning for nine days. Blood fructose disappearance curves, blood pyruvate and phosphorus levels, and urinary fructose excretion were similar to those found in normal subjects and were unchanged after nine days. Similar studies following nine days of oral administration also revealed no loss of fructose tolerance. Fructose was utilized better than glucose administered by either route. Blood fructose disappearance curves were not altered by insulin. For two weeks the patient received a constant diet to which 138 gm. of either fructose or glucose was added on alternate days. When the sugars were thus distributed in the diet, the twenty-four-hour urinary excretion of hexose did not demonstrate any striking advantage of fructose over glucose. Possible explanations for this apparent discrepancy will be presented. The implication of these findings with regard to the prevailing concepts of carbohydrate metabolism and the site of insulin action will be discussed. EFFECTS OF P-(DI-N-PROPYLSULFAMYL) BENZOIC ACID(BENEMID@)ON FREE AND TOTAL SULFONAMIDE PLASMALEVELS. A. P. Crosley, Jr., M.D., G. M. Bayne, M.D., * S. Carfagno, M.D. * and W. P. Boger, M.D. (From the Norristown State Hospital, Norristown, Pa.) Enhancement of plasma-penicillin levels by benemid@ is of therapeutic advantage in a number of clinical states. The likelihood that sulfonamides may be employed concomitantly with benemid and penicillin, and the structural similarity between sulfonamides and other compounds whose renal transport is affected by benemid suggested exploring the effects of this agent upon sulfonamide plasma concentrations following oral and intravenous administration

for Clinical Research of triple sulfonamide combinations. Twelve individuals were used as their own controls in a cross-over type of experiment. It seemed advantageous in a preliminary investigation of this kind, designed to test an effect upon the sulfonamide group of compounds, to select a triple mixture rather than a single sulfonamide. Such triple sulfonamide mixtures currently enjoy a wide use based upon their relative freedom from urinary complications. There is little in the literature on the plasma concentrations attained with such combinations. Following intravenous administration of a single dose of the sulfonamides there was an increase in the total sulfonamide levels during benemid administration, amounting to a mean difference of 1.44 mg. per cent. With an orally administered mixture benemid caused an increase in both free (mean difference-2.18 mg. per cent) and total sulfonamide (mean difference-4.56 mg. per cent) plasma levels. These differences are statistically significant (p < .OOl). The benemid effect was maximal on the third day and remained constant thereafter. The clinical significance of these data will be discussed. EXPERIENCE WITH A STANDARDIZED BROMSULFALEIN PLASMA CLEARANCE METHOD AS A SENSITIVETEST OF LIVER FUNCTION.J. W. Culbertson, M.D., T. L. Welton, M.D., * K. H. Kinard, M.D. * and J. G. Easton, M.D.* (From the Cardiovascular Lab., State Univ. Iowa College of Medicine, Iowa City, Ia.) Plasma clearance rate of bromsulfalein represents the state of both liver circulation and hepatocellular metabolism and is influenced by changes in either. Thus it measures actual function at the time of testing (rather than reserve functional capacity) and promptly reflects acute changes in hepatocellular excretory activity during experimental observation. Standardization is accomplished by infusing intravenous BSP constantly at 2.5 mg./min./sq.M., allowing twenty minutes for equilibration and pilot blood sampling, and drawing venous (or arterial) blood samples at thirty, forty, fifty and sixty minutes. Calculations are made from plasma concentration, its rate of change and the infusion rate. C&r is expressed in ml./ minute. Thirty-eight hospitalized patients were studied. Nineteen men (ages 17-75, av. 36) ranged from 163 to 955 (average 610). Nineteen women (ages 16-57, av. 34) ranged from 160 to 1,054 (average 489). Distribution was rather AMERICAN

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