The bioavailability and the clinical usefulness of the P administered by nasal spray were investigated. Ten healthy menopausal women received an IN spray administration (4 doses of an oleic P solution 20 mg/mL, corresponding to nearly 11.2 mg of P) and the circulating P levels were calculated. Sixty minutes after administration, the maximum concentration (CMax, 3.75 +/- 0.214 ng/mL) was reached. High P levels (greater than 2 ng/mL) lasted until 360 minutes, and the AUC 0 to 720 was 1,481.6 +/- 343 ng.h/mL. Progesterone administration by spray formulation has proven to be effective in reaching therapeutic levels and to be acceptable to patients and, probably, clinically safe.
PIP: The bioavailability of progesterone administered by a nasal dose was investigated in 10 healthy menopausal women (average age. 56.4 years). Each woman received 2 spray doses per nostril, for a total progesterone dosage of 11.2 mg. Physiological circulating progesterone levels (greater than 2 ng/mL) were achieved within 2 minutes after intranasal spray administration, lasted an average of 6 hours, and returned to baseline values after 12 hours. The highest mean circulating level of progesterone was achieved at 60 minutes (3.750 + or - 0.214 ng/mL) and a secondary peak was recorded at 240 minutes (2.700 + or - 0.244 ng/mL). Variability in circulating levels of progesterone after spray administration did not exceed 34% in any patient until the final measurement point (720 minutes). There was no evidence of nasal irritation, but all subjects complained of the unpleasant taste of the spray. The effectiveness of intranasally administered progesterone appears due to progesterone's high solubility in the oleic carrier and the wide surface of the nasal mucosa covered by the nebulized solution. Considering the liver first-pass metabolic effect when progesterone is administered orally and the insufficient bioavailability of progesterone produced by rectal or vaginal administration, further investigation of the nasal spray approach is urged.