Pharmacokinetics of Implanon®: An integrated analysis

doi:10.1016/S0010-7824(98)00120-6

Contraception

Volume 58, Issue 6, Supplement 1, December 1998, Pages 85S-90S

https://doi.org/10.1016/S0010-7824(98)00120-6 Get rights and content

Abstract

The aims of this paper were to present data on the pharmacokinetics, clearance, bioavailability, and in vivo absorption of etonogestrel (ENG); to present the results of a longitudinal analysis of the plasma concentration-time curves of ENG; and to present the results of a cross-sectional analysis on the association of body weight with serum ENG concentrations.

Implanon® had an absorption rate of almost 60 μg/day after 3 months, which slowly decreased to 30 μg/day at the end of 2 years. The bioavailability over this period of time was constant and close to 100%. The clearance remained around 7.5 L/h. With a bioavailability and clearance that remained constant, it was concluded that accumulation of ENG does not occur.

After Implanon insertion, serum concentrations increased within 8 h to concentrations associated with ovulation inhibition. Maximum mean serum concentrations (C_max) amounted to 813 pg/mL and the time (t_max) to reach C_max was 4 days. After reaching C_max, ENG serum concentrations declined to about 196 pg/mL at the end of the first year, followed by a slow decline to 156 pg/mL at the end of the third year. After removal of Implanon, serum ENG concentrations declined to levels less than the detection limit of the assay (20 pg/mL) within 1 week. Lower body weight was associated with higher serum ENG concentrations.

Introduction

Subdermal implants for long-term contraception should provide a continuous and stable release of the active substance, to reduce the over- and underdosing periods that may occur with intermittent oral administration.1 NV Organon has developed an implant containing the progestogen etonogestrel (ENG). By virtue of the release of ENG, the implant provides contraceptive efficacy during a period of 3 years. The contraceptive effect is achieved primarily by ovulation inhibition.

The aims of this paper were to present data on the pharmacokinetics, clearance, bioavailability, and in vivo absorption of ENG before, during, and after implant use; to present the results of the longitudinal analysis of the plasma concentration-time curves of ENG; and to present the results of a cross-sectional analysis on the association of body weight with serum ENG concentrations.

Section snippets

Study medication

Implanon® is a single-rod implant with a length of 4.0 cm length and an outside diameter of 2.0 mm, which contains 68 mg of ENG (3-ketodesogestrel, the biologically active metabolite of desogestrel) in a core that is covered by an ethylene vinyl acetate (EVA) membrane. The in vitro release profile of the implant is characterized by an initial in vitro release rate of 60–70 μg/day, followed by a gradual decline to about 40, 34, and 25–30 μg/day at the end of the first, second, and third year,

Intravenous administration

The results of this study showed that Implanon has an absorption rate of almost 60 μg/day after 3 months, which slowly decreases to 30 μg/day at the end of 2 years (Table 2). The bioavailability over this period of time was constant and close to 100%. The clearance remained around 7.5 L/h. With a bioavailability and clearance that remained constant, it was concluded that accumulation of ENG does not occur.

The pharmacokinetic parameters calculated from the concentrations following intravenous

Discussion

As with other implants, after an initial period of higher ENG levels, the serum concentrations in women using Implanon show a gradual decrease over time. With a bioavailability that remained constant and close to 100% and a clearance of around 7.5 L/h, it is evident that there is no accumulation and that the decrease in serum concentrations is only caused by the slightly lowering release rate over time.

The half-life of elimination of ENG of around 25 h is much lower than the 41.7 h found for

Conclusion

The release of ENG from Implanon is well controlled. Implanon provides an in situ ENG absorption rate of almost 60 μg/day after 3 months, which slowly decreases to 30 μg/day at the end of 2 years. The bioavailability over this period of time was constant and close to 100%. The clearance was rather constant and approximately 7.5 L/h. With a bioavailability and clearance that remained constant, it was concluded that accumulation of ENG does not occur.

After insertion, serum ENG concentrations

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Original Research ArticlesPharmacokinetics of Implanon®: An integrated analysis

Abstract

Introduction

Section snippets

Study medication

Intravenous administration

Discussion

Conclusion

J Steroid Biochem Molec Biol

Contraception

Fertil Steril

Contraception

Contraception

Original Research Articles
Pharmacokinetics of Implanon®: An integrated analysis