Local transport of testosterone from the nasal mucosa to the carotid blood and the brain in the pig
Local counter current transfer of substances between venous and arterial vessels has been found in the perihypophyseal vascular complex after administration into the supraorbital vein. The present experiments investigate whether similar transfer could be found after nasal administration of testosterone. Experiments were conducted on the model of isolated pig's head perfused with autologous blood through one carotid artery. Tritium labelled testosterone was infused onto the nasal mucous. Radioactivity was measured in blood samples collected from the contralateral carotid artery (indicator of transfer), in the venous effluent from the jugular veins (indicator of absorption), and in tissue samples from the olfactory bulb, olfactory triangle, hypothalamus, mammillary body, cortex, pons, cerebellum, neurohypophysis, adenohypophysis, pia vessels and perihypophyseal vascular complex. The absorption was 11.4 ±4.6 per cent (mean ± SEM) and 0.4 ±0.3 per cent of the instilled testosterone was transferred during the 25 min collection period. The uptake of radioactivity was seen in many of the brain tissue samples representing the brain, pituitary, pia vessels and cavernous sinus - carotid rete complex, although a clear pattern was not seen. Nasally administered drugs may thus reach the brain in a relatively higher concentration than it reaches the rest of the body. This makes targeted treatment of the brain a distinct possibility. Additionally, the treatment will decrease the first-passage metabolism in the liver.