We have investigated the urinary excretion, blood levels, protein binding, and chromatographic behavior of chlorpropamide, a new sulfonylurea. This was accomplished by administering this drug to nondiabetics and to diabetic patients. Work by others has shown that tolbutamide, another sulfonylurea, has a serum half time of 4 hours, and that it is carboxylated a t the p-methyl group irz v~v o . '~~ On the other hand, carbutamide has a longer serum half time of 33 hours, and the p-amino group is acetylated in vivo.' To our knowledge there are no published reports concerning the metabolic fate of chlorpropamide in man.
MethodsThe radioactive chlorpropamide used in these experiments had an initial specific activity of 66.6 mg./mc. I t was given as a water solution with sufficient carrier added so that 20 p c of sulfur-35 equaled 250 mg. of chlorpropamide.Four nondiabetic patients without renal disease were given a single oral dose of 250 mg. of radioactive chlorpropamide containing 20 pc of sulfur-35.Three stable diabetic patients: subject No. 1, 45 years old, received 500 mg. tolbutamide twice daily; subjects Nos. 2 and 3, 71 and 64 years old, respectively, received 250 mg. of chlorpropamide daily as therapy. On the day of the test each patient received orally one dose of 250 mg. of radioactive chlorpropamide. No further chlorpropamide was given during the test period.( u ) A 41-year-old diabetic patient who had not received chlorpropamide prior to this test was given intravenously 20 pc of radioactive chlorpropamide without added carrier. One tablet of 250 mg. of chlorpropamide was given orally a t the same time. (b) A 71-year-old diabetic was treated in the same way as the patients of Group 1.The radioactive samples were counted with an automatic micromil gas flow G.M. tube with an average background of 14 cpm, using a preset count of 1000. Sufficient recounts were obtained to give a 5 per cent average counting error or, in the case of the weaker samples, a sufficient number of recounts to obtain a t least 3 count rates that were within 1 cpm of the median count rate. The mean of these median values was considered to be the true count rate. Each sample was weighed and corrected for self absorption. All serum samples were deproteinized by sodium tungstate and sulfuric acid precipitation prior to plating.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.