Nasal delivery of progestational steroids in ovariectomized rabbits: I. progesterone — comparison of pharmacokinetics with intravenous and oral administration

Abstract

Transnasal delivery of progesterone was studied in rabbits employing a nasal spray and a specially designed controlled delivery nasal device. The device is cylindrically shaped for better insertion into the nasal cavity, and is walled with a microporous membrane to permit controlled delivery of progesterone from a suspension formulation to the nasal mucosa. Ovariectomized New Zealand white rabbits were chosen as the animal model after preliminary studies which indicated that ovary-intact rabbits have significant fluctuations in endogenous progesterone levels. The pharmacokinetics of progesterone were evaluated in a cross-over study comparing i.v., oral, nasal device and nasal spray treatments. Using i.v. data as the reference, the systemic bioavailability of progesterone delivered by nasal device and nasal spray was calculated to be 72.4% and 82.5%, respectively. This was substantially greater than the oral bioavailability of 7.9%. The nasal device was observed to achieve a more prolonged and elevated plasma level of progesterone than the other routes of administration. The nasal spray and nasal delivery device will be employed as tools to study and to compare the effect of immediate and controlled drug release on nasal bioavailability of drugs.