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

Author(s)

de Jesus Antunes, Natalicia ^[1] ; de Oliveira Filho, Raimundo Vieira ^[1] ; de Oliveira Ilha, Jaime ^[2] ; Moreno, Ronilson A. ^[3] ; Nahoum, Andre Felipe ^[1] ; Wedemeyer, Ralph-Steven ^[4] ; Warnke, Andre ^[4] ; De Nucci, Gilberto ^{[5, 1, 6]}

Affiliation

^[1] State Univ Campinas UNICAMP, Dept Pharmacol, Fac Med Sci, Alexander Flemming St 105, BR-13083881 Campinas, SP - Brazil

^[2] Galeno Res Unit, Campinas - Brazil

^[3] Univ Estadual Campinas, Sch Food Engn, Dept Food Sci, Campinas - Brazil

^[4] SocraTec R&D GmbH, Oberursel - Germany

^[5] Univ Sao Paulo, Inst Biomed Sci, Sao Paulo - Brazil

^[6] Sao Leopoldo Mand SLMANDIC, Fac Med, Campinas - Brazil

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF CONTRACEPTION AND REPRODUCTIVE HEALTH CARE; v. 26, n. 3 FEB 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 16/22506-1 - Metabolism of dapaconazole
• Grantee: Natalícia de Jesus Antunes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral