BX-912 studies are needed to determine whether other biomarkers

Edication can not be regarded BX-912 as the first choice of COC for novice users due to problems of cooperation Ts and respect, but may have an advantage to be seen for women who are bleeding and other side effects with COC are looking for shorter and / or lighter menstrual cycles. Epidemiological studies are needed to determine whether other biomarkers lead to clinically significant results between different E2V/DNG and other available COCs. Quantitatively the most important representatives of the E1 S big pool of s is circulating estrogen conjugates, which may in estrogen Active converted. Blood samples from DNG, E2, E1 and E1-S before treatment study days 1, 8, 11 and 13 17 were collected, were taken further samples at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing on study days 11 and 17 Zus Tzlich were blood samples to determine plasma concentrations of rifampicin, collected before treatment to 12 days of the study, and 8 hours after dosing on study days 12 16. 2.3.1.2. Study 2. Blood serum concentration of DNG, E2, E1 and E1 S determined before treatment study days 1, 7 and 5 12 14 were collected, were additionally USEFUL samples 0.5, 1, 1, 5, 2, 3, 4, 6 , 8, 10, 12, 16 and 24 hours following dosing in the study days 7 and 14 In addition, blood samples, plasma concentrations of ketoconazole or erythromycin determine before treatment is collected in the study days 8 and 12 14. 2.3.2. Pharmacokinetic blood sample processing, which became the serum concentrations of DNG, E2, E1 and E1 to be determined to be S, in, plastic, easy to use pipes Monovette collected. Samples that are used to give concentrations of rifampicin, ketoconazole or erythromycin were to determine plasma was heparincontaining in sodium, glass, single use R Collected Hrchen Monovette. After treatment the samples were frozen prior to analysis. 2.3.3. Bioanalytical Methods 2.3.3.1. Study 1 Determination of bio E2, E1 and E1 was S, and rifampicin performed by PPD Development. The serum concentrations DNG was conducted by the study sponsor. Serum concentrations of E2, E1 and E1-S were validated procedures Including Lich liquid chromatography with mass spectrometry performed in duplicate. The lower and upper limits of quantification were 2.5 pg / ml and 250 pg / ml for E2, 5.0 pg / ml and 500 pg / ml for E1 and 50 pg / ml and 5000 pg / ml for E1 S. inter-assay coefficients of variation and inter-assay for E2, E1 and E1-S were 94.1% and 98.6% 0.66% 8.51%, 99.1% to 103% and 0.82% 8, 11% and 99.1% to 115% and 3.92% 9.36%, respectively. Serum concentrations of DNG were validated using a radioimmunoassay wettbewerbsf compatibility available based on the detection of 3H labeled tracer bound to DNG DNG polyclonal antibody Determined body. The samples were extracted with ethyl ether before radioimmunoassay. The separation of antique Body, bound-free dienogest was obtained by adding a suspension of activated charcoal / dextran-sedimentation and charcoal by centrifugation. The supernatant was subjected to radiometric analysis. DNG concentrations were measured using a standard reference curve. The LLOQ was 0.30 ng / ml, the ULOQ was 5.0 ng / ml. The inter-assay coefficients of variation and inter-assay for DNG amount was 89% to 98% and 5.6% to 14.1%.