Single and multidose pharmacokinetic study of a vaginal micronized progesterone insert (Endometrin) compared with vaginal gel in healthy reproductive-aged female subjects.

Objective: To determine pharmacokinetic profiles of two times a day and three times a day dosage regimens of Endometrin, a micronized progesterone vaginal insert for luteal support in assisted reproductive technology, compared with a gel.

Design: A single-center, randomized, open-label, single-day, and multiple-day (5 days) parallel design pharmacokinetic study.

Setting: University clinical research unit.

Patient(s): Three groups of six healthy subjects, ages 18 to 40 years.

Intervention(s): Endometrin vaginal inserts two times a day or three times a day, or gel daily.

Main Outcome Measure(s): Pharmacokinetic profiles.

Result(s): Progesterone serum concentrations increased rapidly following administration of Endometrin vaginal insert, producing higher peak concentrations (Cmax) and clearing faster than gel. On the single day of dosing, mean Cmax was 17.0+/-2.7 ng/mL in the two times a day group, 19.8+/-2.9 ng/mL in the three times a day group, and 6.82+/-1.69 ng/mL in the gel group. Endometrin treatments reached steady state within the first 2 days (24-36 hours), much more rapidly than the gel, which had not reached steady state by 5 days. At 5 days, the Endometrin treatments produced sustained progesterone concentrations exceeding 10 mg/mL across 24 hours.

Conclusions: Endometrin vaginal inserts reached higher Cmax, produced greater systemic exposure (area under the curve 0-24), achieved steady state more rapidly, and cleared more rapidly after termination of therapy than the comparator.