The metabolism and disposition of [2-¹⁴C]diazepam in the streptozotocin-diabetic rat

Abstract

1. The oral administration of [2-¹⁴C]diazepam to streptozotocin (STZ)-diabetic rats resulted in decreased faecal and biliary levels of metabolites with a concomitant rise in urinary radioactivity when compared to control values. This situation was reversible upon insulin treatment.

2. The increased urinary metabolite excretion could not be ascribed to the diuresis observed in STZ-diabetic rats.

3. No alteration in the phase I or II routes of [¹⁴C]diazepam metabolism in diabetic animals was observed either in vivo or in vitro.

4. Following i.v. administration of [2-¹⁴C]diazepam, blood ¹⁴C levels in diabetic rats were elevated above those observed in normal animals.