Unchanged Protein Binding and the Increase of Serum Diazepam Levels after Food Intake

Abstract

Seven subjects received diazepam 0.3 mg/kg intravenously twice with a 2-week interval between the doses. The subjects ingested a fatty or carbohydrate meal in a cross-over fashion 4 hours after the injection on both experimental days. Venous blood samples were drawn 2, 3, 4, 5 and 6 hours after the injection of diazepam for measurement of the serum levels of total and free (unbound) diazepam, N-desmethyldiazepam, and free fatty acids. Serum levels of diazepam decreased progressively with time until the food intake, after which a significant (P less than 0.01) postprandial increase (average 23%) occurred with both diets as compared to the preprandial levels at 4 hours (average 240 ng/ml). Serum levels of free fatty acids decreased significantly both after a fatty (P less than 0.01) and a carbohydrate (P less than 0.05) meal. Diazepam was extensively (96 to 98%) bound to proteins and no changes in its protein binding was found. It is concluded that the late impairment of psychomotor skills that occurs with an increase in the diazepam serum level after its intravenous administration is due rather to its re-mobilization from a storage site than to variations in its protein binding.