NASAL SPRAY ADMINISTRATION OF UNMODIFIED PROGESTERONE - EVALUATION OFPROGESTERONE SERUM LEVELS WITH 3 DIFFERENT RADIOIMMUNOASSAY TECHNIQUES

A 11.20 mg dose of progesterone was administered by nasal spray (NS) t o six healthy postmenopausal women. Serial blood samples were collecte d and plasma progesterone was assayed by radioimmunoassay (RIA) accord ing to three different procedures. In the first, RIA was carried out d irectly on plasma aliquot (Method A), in the second after diethyl ethe r extraction (Method B) and the third, after diethyl ether extraction and Celite column chromatography (Method C). The mean serum peak level (C-Max) calculated with Method A (2.87 +/- 1.14 ng/ml) was higher tha n that obtained with both Method B (2.24 +/- 0.76 ng/ml) and C(1.58 +/ - 0.76 ng/ml; P < 0.05); similarly the area under the curve (AUC) meas ured with Method A (695.79 +/- 348.24 ng h/ml) was higher than that ob tained with both Method B (390.12 +/- 95.16 ng h/ml) and C (243.71 +/- 82.97 ng h/ml; P < 0.02). On the other hand, progesterone serum level s measured with Method C peaked earlier than those observed with Metho ds B and A (21.67 +/- 19.40, 25.83 +/- 18.55 and 35 +/- 20.70 min, res pectively). These data are consistent with the high specificity of Met hod C for progesterone whereas the other methods could overestimate th e progesterone serum levels probably measuring also progesterone metab olites particularly 5 alpha and 5 beta-dihydroprogesterone. This study confirmed the rapid absorption of progesterone across the nasal mucos a avoiding the first-pass liver metabolism; however, a 'first-pass eff ect' of the nasal mucosa should be taken into consideration when proge sterone is delivered by the nasal route because probably a significant portion of progestational effects are due to its active metabolites.