An initial pharmacokinetic study with a Metered Dose Transdermal System® for delivery of the progestogen Nestorone® as a possible future contraceptive

Fraser, Ian S.; Weisberg, Edith; Kumar, Narender; Kumar, Sushma; Humberstone, Andrew J.; McCrossin, Louise; Shaw, Deborah; Tsong, Y.Y.; Sitruk-Ware, Regine

doi:10.1016/j.contraception.2007.08.006

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Volume 76, Issue 6 , Pages 432-438, December 2007

An initial pharmacokinetic study with a Metered Dose Transdermal System® for delivery of the progestogen Nestorone® as a possible future contraceptive☆

Ian S. Fraser
- Department of Obstetrics and Gynaecology, University of Sydney, NSW 2006, Australia
- Sydney Centre for Reproductive Health Research, Research Division of Family Planning NSW, Ashfield, NSW 2131, Australia
- Corresponding author. Tel.: +61 2 9351 2478; fax: +61 2 9351 4560.
Edith Weisberg
- Department of Obstetrics and Gynaecology, University of Sydney, NSW 2006, Australia
- Sydney Centre for Reproductive Health Research, Research Division of Family Planning NSW, Ashfield, NSW 2131, Australia
Narender Kumar
- Center for Biomedical Research, Population Council, Brooklyn, NY 10021, USA
Sushma Kumar
- Center for Biomedical Research, Population Council, Brooklyn, NY 10021, USA
Andrew J. Humberstone
- Acrux Ltd., West Melbourne, Vic 3003, Australia
Louise McCrossin
- Acrux Ltd., West Melbourne, Vic 3003, Australia
Deborah Shaw
- Centre for Pharmaceutical Research, University of South Australia, North Terrace, Adelaide, SA 5000, Australia
Y.Y. Tsong
- Center for Biomedical Research, Population Council, Brooklyn, NY 10021, USA
Regine Sitruk-Ware
- Center for Biomedical Research, Population Council, Brooklyn, NY 10021, USA

Received 6 August 2007; received in revised form 9 August 2007; accepted 15 August 2007. published online 12 November 2007.

Abstract

Background

Transdermal delivery of steroids is gaining popularity for contraception and hormone replacement therapy. This study aimed to test metered spray delivery of a precise dosage of Nestorone® (NES) progestogen as a possible transdermal progestogen-only contraceptive.

Study Design

Six healthy postmenopausal volunteers, not recently using any hormonal therapies, comprise the sample for this study. Each subject was studied on two occasions with multiple blood sampling for assay of NES over a 24-h period: on the first occasion, after a single dosage of 3×90 μL NES sprays using a specially devised, precisely metered delivery device; on the second occasion, following the fifth in a series of five daily transdermal dosages of 3×90 μL of NES spray. Conventional pharmacokinetic parameters were calculated. NES was assayed in serum using a specific radioimmunoassay.

Results

Mean serum levels of NES peaked at around 20 h following dosing, and levels plateaued at 285–290 pmol/L after 4–5 days of daily spray application. All subjects achieved satisfactory serum levels, although substantial intersubject variation was noted. The apparent elimination half-life of NES after the last dose on Day 5 was 26.8 h. No unexpected adverse events were encountered.

Conclusion

This early pharmacokinetic trial of a new transdermal steroid delivery system has demonstrated the feasibility of achieving serum levels of NES sufficient to block ovulation and potentially provide effective contraception.

Keywords: Hormonal contraception, Transdermal delivery, Pharmacokinetics, Nestorone