diately before ovulation is to occur, ella postpones follicular rupture. The likely primary mechanism of action of ulipristal acetate for emergency contraception is therefore inhibition or delay of ovulation; however, alterations to the endometrium that may affect implantation may also contribute to efficacy.
12.2 Pharmacodynamics
Ulipristal acetate is a selective progesterone receptor modulator with antagonistic and partial agonistic effects (a progesterone agonist/antagonist) at the progesterone receptor. It binds the human progesterone receptor and prevents progesterone from occupying its receptor.
The pharmacodynamics of ulipristal acetate depends on the timing of administration in the menstrual cycle. Administration in the mid-follicular phase causes inhibition of folliculogenesis and reduction of estradiol concentration. Administration at the time of the luteinizing hormone peak delays follicular rupture by 5 to 9 days. Dosing in the early luteal phase does not significantly delay endometrial maturation but decreases endometrial thickness by 0.6 ± 2.2 mm (mean ± SD).
12.3 Pharmacokinetics
Absorption
Following a single dose administration of ella in 20 women under fasting conditions, maximum plasma concentrations of ulipristal acetate and the active metabolite, monodemethyl-ulipristal acetate, were 176 and 69 ng/ml and were reached at 0.9 and 1 hour, respectively.
Figure 1: Mean (± SD) Plasma Concentration-time Profile of Ulipristal Acetate and Monodemethyl-ulipristal Acetate Following Single Dose Administration of 30 mg Ulipristal Acetate
Table 2: Pharmacokinetic Parameter Values Following Administration of ella (ulipristal acetate) Tablet 30 mg to 20 Healthy Female Volunteers under Fasting Conditions
Mean (± SD)
Cmax
(ng/ml)
AUC0-t
(ng•hr/ml)
AUC0-∞
(ng•hr/ml)
tmax
(hr)*
t1/2
(hr)
Ulipristal acetate
176
(89)
548
(259)
556
(260)
0.9
(0.5-2.0)
32
(6.3)
Monodemethyl-ulipristal acetate
69
(26)
240
(59)
246
(59)
1.00
(0.8-2.0)
27
(6.9)
Cmax = maximum concentration
AUC0-t = area under the drug concentration curve from time 0 to time of last determinable concentration
AUC0-∞ = area under the drug concentration curve from time 0 to infinity
tmax = time to maximum concentration
t1/2 = elimination half-life
* Median (range)
Effect of food: Administration of ella together with a high-fat breakfast resulted in approximately 40-45% lower mean Cmax, a delayed tmax (from a median of 0.75 hours to 3 hours) and 20-25% higher mean AUC0-∞ of ulipristal acetate and monodemethyl-ulipristal acetate compared with administration in the fasting state. These differences are not expected to impair the efficacy or safety of ella to a clinically significant extent; therefore, ella can be taken with or without food.
Distribution
Ulipristal acetate is highly bound (> 94%) to plasma proteins, including high density lipoprotein, alpha-l-acid glycoprotein, and albumin.
Metabolism
Ulipristal acetate is metabolized to mono-demethylated and di-demethylated metabolites. In vitro data indicate that this is predominantly mediated by CYP3A4. The mono-demethylated metabolite is pharmacologically activ |
