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

Dienogest (17α-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 ± s D , n = 13) of total serum dienogest. Free levonorgestrel constituted 0.97 ± 0.14% (n = 12) of total serum levonor-gestrel. In an investigation with 47 female volunteers taking Certostat R , 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 hound 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.