Single-dose pharmacokinetics and pharmacodynamics assessment of oestriol and trimegestone containing vaginal rings in healthy women with childbearing potential.

Abstract

PURPOSE:

To evaluate the pharmacokinetics and pharmacodynamics of oestriol (E3) and trimegestone (TMG) in healthy women after application of three different vaginal rings over 21 days. The vaginal rings had a nominal delivery rate of 0.413/0.050 mg/day (Test 1), 0.311/0.090 mg/day (Test 2) and 0.209/0.137 mg/day (Test 3) E3/TMG.

METHODS:

Thirty-five healthy women were randomised to receive a single application of Test 1, 2 or 3 (Clinical Trial NCT03343912). The E3 and TMG plasma concentration was determined by LC-MS/MS. Oestradiol (E2) and progesterone (PG) serum concentrations, and bleeding patern were determined as pharmacodynamic parameters. Safety was assessed by evaluation of adverse events and local tolerability.

RESULTS:

The total and maximum exposure of E3 and TMG increased in a proportional ratio to dose. However, not in a magnitude which was expected from the dose differences for E3. During Test 2 and 3 treatment all E2 and PG values remained on a well suppressed level until end of treatment. E2 and PG serum levels increased distinctly earlier after ring removal with Test 1 compared to Test 2 and 3. Test 3 achieved 95.24% of "no bleeding" days under treatment followed by Test 1 (91.67%), and Test 2 (86.15%).

CONCLUSIONS:

The Test 3 formulation presented the best dose combination of E3/TMG for contraception. Moreover, all vaginal rings were well tolerated.

• Authors: Natalícia de Jesus Antunes, Raimundo Vieira de Oliveira Filho, Jaime de Oliveira Ilha, Ronilson A Moreno, André Felipe Nahoum, Ralph-Steven Wedemeyer, André Warnke, Gilberto De Nucci
• Journal: The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception (Eur J Contracept Reprod Health Care) Vol. 26 Issue 3 Pg. 184-194 (Jun 2021) ISSN: 1473-0782 [Electronic] England
• PMID: 33645377 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Contraceptive Agents, Female
• Estrogens
• trimegestone
• Progesterone
• Estradiol
• Promegestone
• Estriol

Topics

• Administration, Intravaginal
• Adult
• Chromatography, Liquid
• Contraceptive Agents, Female (administration & dosage)
• Contraceptive Devices, Female
• Estradiol (blood)
• Estriol (pharmacokinetics, pharmacology)
• Estrogens (blood, metabolism)
• Female
• Humans
• Progesterone (blood)
• Promegestone (analogs & derivatives, pharmacokinetics, pharmacology)
• Tandem Mass Spectrometry