Local transfer of diazepam, but not of cocaine, from the nasal cavities to the brain arterial blood in rats.

Nasal administration to rats of small molecules (tritiated water, tyrosine, and propanol) results in a higher concentration in the brain arterial blood than in other arteries. The preferential distribution is based on a counter current transfer, which takes place between nasal vein blood and brain arterial blood in the cavernous sinus-carotid artery complex. The present experiments attempt to document that drugs may also be transferred by this system. Groups of 10 large male rats were anaesthetised and intubated. Two catheters were inserted into the same carotid artery, one tip pointing towards the head, the other towards the heart. Parallel blood samples were obtained every 30 sec. for 10 min. after nasal administration of radioactively labelled diazepam or cocaine, and the plasma radioactivity measured. Control groups received the drugs intravenously. The uptake of diazepam was rapid, while cocaine uptake was slow. The average ratio between the radioactivity of parallel samples (R: "Head" plasma/"Heart" plasma) in rats treated with nasal diazepam was 1.12+/-0.04, 181 (average+/-S.E.M., n) for the whole 10 min. period and 1.20+/-0.05, 96 for the second half of the sampling period. The increase of 12 and 20% is highly significant. The intravenous ratio for diazepam and both R's for the cocaine groups were not significantly different from 1.00. The present experiments show that nasal administration of diazepam induces a relatively higher concentration in the brain arterial blood than in parallel samples obtained from another artery. A preferential, first-pass distribution to the brain after nasal administration of diazepam may thus exist.