Non-protein bound dienogest in serum and salivary dienogest in women taking the oral contraceptives Certostat and Valette.

Dienogest (17 alpha-cyanomethyl-17-hydroxy-4,9-estradien-3-one) is the progestagen component of the oral contraceptives Certostat and Valette. In contrast to other 19-norsteroid progestagens like levonorgestrel, norethisterone, gestodene and 3-ketodesogestrel, dienogest does not bind to sexual hormone binding globulin (SHBG). The absent binding to SHBG results in a high portion of free, non-protein bound dienogest in serum. In female volunteers taking the oral contraceptives Certostat and Trisiston, the part of non-protein bound dienogest and levonorgestrel, respectively, in serum was determined by the method of centrifugal ultrafiltration. The portion of free dienogest was found to be 9.55 +/- 0.95% (m +/- SD, n = 13) of total serum dienogest. Free levonorgestrel constituted 0.97 +/- 0.14% (n = 12) of total serum levonorgestrel. In an investigation with 47 female volunteers taking Certostat, serum total dienogest was quantified by a specific radioimmunoassay and free dienogest in serum by centrifugal ultrafiltration. In the serum samples with dienogest concentrations in the range of 4.1-57.7 ng/ml, the part of free, non-protein bound dienogest was found to be 8.90 +/- 0.54% of serum total dienogest. There is a high correlation between serum total dienogest and free dienogest (r = 0.989). In another investigation with 20 female volunteers taking the contraceptive Valette, serum total dienogest and salivary dienogest were quantified by radioimmunoassay and free dienogest in serum by centrifugal ultrafiltration. In the serum samples with dienogest concentrations in the range of 7.5-50.6 ng/ml, the part of free, non-protein bound dienogest was 8.78 +/- 0.77% of serum total dienogest. Salivary dienogest constituted 7.99 +/- 0.94% of serum total dienogest showing a high correlation with serum free dienogest (r = 0.953) and serum total dienogest (r = 0.958). The high portion of non-protein bound compound in serum is a characteristic pharmacokinetic feature of dienogest.