A sequential trial of tolbutamide in hypoproteinaemia in adults.

A definite increase in the glycogen content of the liver with tolbutamide administration in animal experiments has prompted some workers to investigate the action of the drug on liver diseases in man. Such an idea was based on the assumption that augmenting glycogen in the liver must have a beneficial effect on the damaged liver. Knick and Emrich (1957) used tolbutamide, 3 g. daily for three to six weeks, in six cases of chronic hepatitis and six cases of liver cirrhosis without diabetes and reported increased appetite, decrease in serum bilirubin, marked restoration to normal of the serum proteins, and improvement in the bromsulphalein test. Improvement in bromsulphalein excretion was also reported in a diabetic patient by Pote, Anderson, and Cochran (1959). Laszlo, Bruckner, Gorgey, and T6th (1959) treated 50 patients suffering from acute hepatitis and found that decrease in serum bilirubin and recovery time were both hastened by tolbutamide when compared with a similar group of controls. In liver biopsy studies Dobrzanski (1959) noted excess of glycogen in liver cells, diminution of vacuolization of liver cell nuclei, and distinct regression of fatty changes in the liver in 12 tolbutamide-treated diabetic patients. Singh, Sehra, and Bhargava (1961) treated 55 cases of cirrhosis of the liver suffering from anorexia, emaciation, anaemia, hypoproteinaemia, and gross ascites with tolbutamide and reported improvement in appetite in 45 cases (82 %), control of ascites in 42 cases (76 %), weight gain in 36 cases (66 %), increase in serum proteins in 35 cases (64%), and improvement in the haemogram in 24 cases (44%). Liver-function tests showed moderate improvement in 26 cases (47 %) but there was no deterioration in the remaining 29 cases. Bhattacharyya and Mandal (1963) reported comparable results in 10 cases of cirrhosis of the liver from the Calcutta School of Tropical Medicine. Under tolbutamide therapy total serum proteins improved progressively in seven cases, there was initial improvement followed by deterioration in two cases, and practically no change in one case. Rapid improvement in the albumin fraction was a striking feature when the initial serum albumin level was below 2 g. %. It was felt by us that the increase in serum proteins under tolbutamide administration may not necessarily be confined to diseased livers. Thus, pretreatment of rats with tolbutamide had been observed to increase the incorporation of 14C-glycine into protein in liver slices by Recant and Fischer (1957); and DeMeutter, Khachadurian, and Marble (1958) had noticed that tolbutamide injected intravenously into human subjects decreased serum oc-amino-acids. We were, therefore, prompted to try the effect of tolbutamide in the treatment of hypoproteinaemia from any cause. Using the restricted closed design sequential trial technique, advocated by Armitage (1960), we have found the results to be satisfying in malnutrition and malabsorption; previous reports of increase in serum proteins with tolbutamide in cirrhosis of the liver (vide supra) have been confirmed.