Pharmacokinetics of etonogestrel released from the contraceptive implant Implanon

Abstract

Eight healthy women between 22 and 40 years of age participated in this prospective open study of 2 years' duration. Either on or between days 1 to 7 of a spontaneous menses, an intravenous bolus dose of 150 micrograms etonogestrel (3-ketodesogestrel) was given. During days 1-5 of a subsequent spontaneous cycle, the single-rod contraceptive implant (Implanon) was inserted in the upper arm of the volunteer. One year after placement of the implant, another intravenous bolus dose was given (implant in place), and a third bolus dose was given after 2 years, with the implant removed. Frequent serum sampling immediately after the intravenous dosings of etonogestrel was done to study the primary pharmacokinetic parameters, i.e., volume of distribution and clearance, allowing the calculation of the absorption rate and bioavailability of the implant, as a function of time. Results showed that etonogestrel released from Implanon has an absorption rate of approximately 60 micrograms/day after 3 months, which slowly decreases to 30 micrograms/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 may be concluded that there is no accumulation of etonogestrel.

PIP: A total of 2335 women have accumulated 58,135 cycles of exposure to Implanon--a single-rod contraceptive implant containing 68 mg of etonogestrel with a 3-year duration of action. To assess this agent's pharmacokinetics, 8 women received 3 bolus injections: the first 1-2 months before implant insertion, the second after 12 months of use with the implant still in place, and the third after implant removal at 24 months. Etonogestrel concentrations decreased gradually over the 2 years of use. The absorption rate of about 30 mcg/day after 3 months of use decreased to 30 mcg/day at the end of 2 years. With a bioavailability that remained constant at about 95% and a clearance of about 7.5 L/hour, it can be assumed that there is no accumulation of steroid drug and that decreased serum concentrations are caused only by a slight lowering in release rate over time. The half-life of elimination was 25 hours--significantly lower than the 41.7 hours associated with Norplant implants.