Nasally-administered progesterone: comparison of ointment and spray formulations

Abstract

The aim of the study was to compare the bioavailability and clinical usefulness or progesterone (P) administered nasally in spray or ointment form. Twenty healthy post-menopeusal women were randomly allocated to treatment by either intranasal spray (4 doses of an oil-based P solution at a concentration of 2 mg/0.1 ml, corresponding to a total dose of approximately 11 mg of P) or an ointment (quantity 0.1 ml, P concentration 20 mg/0.1 ml). Circulating P levels were calculated at various time intervals following administration. The spray formulation yielded a mean maximum concentration (CMax) of 3.75 ng/ml after 60 min (TMax) and the area under the curve (AUC) 0–720 min was 1481.6 ± 343 ng · h/ml. The ointment yielded a mean CMax of 1.19 ng/ml at TMax = 30 min, the AUC 0–720 value being 404.35 ± 148 ng · h/ml. The study findings confirmed that the intranasal route is a potentially useful alternative for the administration of natural sex steroid hormones, making it possible to avoid first-pass liver metabolism. P administered by spray showed greater bioavailability than it did when administered in ointment form, while both formulations seemed to be acceptable to patients and were probably clinically safe.