Effect of Food and Repeated Injections on Serum Diazepam Levels

Diazepam 0.3 mg/kg was administered intravenously three times at intervals of 14 days into seven healthy volunteers. Five hours after injection the subjects ingested either 330 ml of mineral water, mineral water in combination with 2 rusks, or 330 ml of fatty milk with an egg hamburger. Diazepam and N‐ desmethyldiazepam levels were measured in serum samples drawn at 4, 5, 6, 7 and 8 hours after administration of the drug. At the same time the ability to discriminate flickering light was measured, and the feeling of tiredness was recorded. The serum diazepam levels declined regularly as a function of time after mineral water, but both kinds of food significantly elevated the serum diazepam level from the sixth hour onwards. The ability to discriminate flickering light was not modified. Serum N‐desmethyldiazepam levels were significantly elevated after the second and third injections as compared with the first injection. Serum diazepam levels were not lowered. The present findings could be explained by an enterohepatic cycle of diazepam, and suggest that diazepam might induce its own metabolism in man.