The pharmacokinetics of FSH-CTP were shown to be proportional with the dose. The elimination half-life was approximately two times longer than that of rFSH. A single dose of FSH-CTP was shown to be safe and able to induce multiple follicular growth accompanied by a dose-dependent rise in serum inhibin-B concentrations.
The gonadotrophin-releasing hormone antagonist Cetrorelix is in advanced clinical development for the control of endogenous gonadotrophin secretion during the course of a fertility programme. The aim of the present study was to investigate the pharmacokinetics and pharmacodynamics of Cetrorelix following single and multiple s.c. administration of different doses. Thirty-six healthy female volunteers received either 0.25, 0.50 or 1.00 mg Cetrorelix, in a first menstrual cycle as single dose and in a second cycle as multiple dose (daily between cycle days 3 and 16). Frequent blood samples were collected for determination of Cetrorelix, follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and progesterone concentrations. Follicular growth was measured by transvaginal ultrasonography. After single administration of each dose, maximum Cetrorelix concentrations (Cmax) were reached after 1 h, and Cmax and area under curve (AUC) increased linearly with the dose. The median terminal half-life ranged from 5 to 10 h in the three different dose groups. FSH, LH, oestradiol and progesterone concentrations were suppressed, with a nadir at 6-12 h after Cetrorelix administration. During multiple administration, Cmax and AUC also showed dose-linearity. The median terminal half-life of Cetrorelix varied between 20 and 80 h. A dose-dependent suppression of FSH, LH and oestradiol concentrations was observed during treatment. After multiple administration, ovulation was delayed for 5, 10 and 13 days in the 0.25, 0.50 and 1.00 mg dose groups, respectively. In conclusion, Cetrorelix showed linear pharmacokinetics, and effectively delayed the LH surge.
BackgroundThe contraceptive efficacy and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg to extend the menstrual cycle and enable management of intracyclic (breakthrough) bleeding (flexibleMIB) was investigated and the bleeding pattern compared with a conventional 28-day regimen and a fixed extended 124-day regimen.Study designThis Phase III, 2-year, multicentre, open-label study randomly (4:1:1) allocated women (aged 18–35 years) to the following regimens: flexibleMIB (24–120 days' active hormonal intake with 4-day tablet-free intervals); conventional (24 days' active hormonal intake followed by a 4-day hormone-free interval); or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval). Primary outcomes included the number of bleeding/spotting days during Year 1 (all regimens) and the number of observed unintended pregnancies over 2 years (flexibleMIB only).ResultsResults were analysed in 1067 women (full analysis set). The mean number of bleeding/spotting days was lower with the flexibleMIB vs the conventional regimen [41.0±29.1 (95% CI 38.8–43.3) vs 65.8±27.0 (95% CI 62.2–69.4) days, p<0.0001; treatment difference −24.8 (95% CI −29.2 to −20.3) days]. The corresponding value for the fixed extended regimen was 60.9±51.1 (95% CI 53.9–67.9) days. The Pearl Index for the flexibleMIB regimen was 0.64 (95% CI 0.28–1.26). All regimens had comparable tolerability profiles.ConclusionsEE 20 μg/DRSP 3 mg administered as a flexible extended regimen with MIB is effective, well tolerated and is associated with statistically significantly fewer bleeding/spotting days and fewer withdrawal bleeding episodes vs EE/DRSP in a conventional 28-day regimen. The flexibleMIB also provided statistically significantly fewer spotting days vs EE/DRSP in a fixed extended 124-day regimen (post hoc evaluation). The flexibleMIB regimen allows women to extend their menstrual cycle and manage their intracyclic (breakthrough) bleeding.
Initiating the use of a DSG progestin-only pill (POP) immediately after UPA reduces the ability of UPA to delay ovulation and thus may decrease its efficacy as EC. If starting a DSG POP after using UPA for EC, and possibly any progestin-only method, consideration should be given to delaying for at least 5 days after UPA intake in order to preserve the ovulation delaying effects of UPA.
The results of these studies identified a four-phasic COC preparation comprising E2V/DNG that provides efficient ovulation inhibition. It is expected that this regimen will lead to an innovative COC containing E2 instead of EE.
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