Prolonged Hypoglycemia Secondary to Tolbutamide

Abstract

A young patient developed prolonged hypoglycemia following only 2 g of tolbutamide given over 2 days. The blood glucose concentration returned to normal only after prolonged glucose infusions of high concentration. Investigations failed to demonstrate glucose intolerance or the presence of an islet cell tumor. A study of the metabolism of tolbutamide in this patient by giving/g of sodium tolbutamide intravenously and measuring serum tolbutamide concentration for 24 hours revealed that the patient had a prolonged biologic half life for tolbutamide of 38 hours, a value that is 9 times that reported in normal subjects. We believe that this patient has a defect in the carboxylation of tolbutamide resulting in a prolonged effect of the drug.