Single dose intranasal administration of 220 micrograms of Nasacort Allergy or Triamcinolone Nasal Spray in normal adult subjects and in adult patients with allergic rhinitis demonstrated minimal absorption of triamcinolone acetonide. The mean peak plasma concentration was approximately ng/mL (range to 1 ng/mL) and occurred at hours post dose. The mean plasma drug concentration was less than ng/mL at 12 hours and below the assay detection limit at 24 hours. The average terminal half life was hours. Dose proportionality was demonstrated in normal subjects and in patients following a single intranasal dose of 110 micrograms or 220 micrograms Nasacort Allergy or Triamcinolone Nasal Spray. Following multiple doses in paediatric patients, plasma drug concentrations, AUC, C max and T max were similar to those values observed in adult patients.
Carcinogenesis/mutagenesis: As seen with other GnRH agonists, nafarelin given parenterally in high doses to laboratory rodents for prolonged periods induced hyperplasia and neoplasia of endocrine organs, including the anterior pituitary (adenoma/carcinoma) of both mice and rats; tumours of the pancreatic islets, adrenal medulla, testes and ovaries occurred only in long-term studies in rats. No metastases of these tumours were observed. Monkeys treated with high doses of nafarelin for one year did not develop any tumours or proliferative changes. Experience in humans is limited but there is no evidence for tumorigenesis of GnRH analogues in human beings.
The major part of the approximately 150 cm 2 surface in the human nasal cavity is covered by respiratory epithelium, across which systemic drug absorption can be achieved. The olfactory epithelium is situated in the upper posterior part and covers approximately 10 cm 2 of the human nasal cavity. The nerve cells of the olfactory epithelium project into the olfactory bulb of the brain, which provides a direct connection between the brain and the external environment. The transfer of drugs to the brain from the blood circulation is normally hindered by the blood–brain barrier (BBB), which is virtually impermeable to passive diffusion of all but small, lipophilic substances. However, if drug substances can be transferred along the olfactory nerve cells, they can bypass the BBB and enter the brain directly.,