Single and multidose pharmacokinetic study of a vaginal micronized progesterone insert (Endometrin) compared with vaginal gel in healthy reproductive-aged female subjects²

METHODS

Design: single-centre, randomised, open-label, single and multiple-day (5 days) parallel design pharmacokinetic study

Participants: 18 healthy women aged 18 to 40

Main outcome measures: pharmacokinetic profiles

Comparator agents: Endometrin^® (100 mg vaginal progesterone tablets; marketed as Lutigest^® in the UK) twice daily (n = 6), three times daily (n = 6), and 8% progesterone vaginal gel (90 mg) daily (n = 6).

RESULTS

Progesterone serum concentrations increased rapidly following administration of Lutigest^®, 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.

Lutigest^® 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, Lutigest^® produced sustained progesterone concentrations exceeding 10 mg/mL across 24 hours.

CONCLUSION

Lutigest^® 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 vaginal gel comparator.

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