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Ethylene-vinyl acetate (EVA) polymeric contraceptive implants (Implanon) containing 3-keto-desogestrel have been prepared aiming at an in vitro initial release rate of 60 micrograms 3-keto-desogestrel/day. These implants are designed to have an intended life-time of 2 years. During a 3-year period, the release of these implants was studied in 4 dogs after subdermal insertion, using plasma clearance of 3-keto-desogestrel assessed after intravenous administration of 3-keto-desogestrel and steady state plasma levels of 3-keto-desogestrel. The mean plasma level of 3-keto-desogestrel decreased gradually during the first year of the study, viz. from 1.64 nmol/1 at 7 days after implantation to 0.69 nmol/l after one year. At the end of the second year, the level had decreased further to 0.45 nmol/l while after 3 years, the mean 3-keto-desogestrel plasma level was 0.42 nmol/l. The calculated mean daily release of 3-keto-desogestrel decreased during the first year from 70 micrograms/day to 30 micrograms/day. During the second and third year, the decrease in release rate was much less, viz. going from 30 micrograms/day to 28 micrograms/day and from 28 micrograms/day to 25 micrograms/day, respectively. This indicates a much more constant release during the second and third year of the study. The calculated cumulative amount of 3-keto-desogestrel released from the implant during the dog study was 34.0 mg. Based on the initial amount of 3-keto-desogestrel in the implant of 68.3 mg, the remaining amount in the implants at termination of the study should be approximately 34.3 mg. Actually, the mean remaining amount of 3-keto-desogestrel was 33.8 mg, which is in very close agreement with the calculated value. Implants from the same batch as used in the in vivo study were also analyzed for the in vitro release at regular times during the 3-year study period. After one year, the in vitro release rate was about 43 micrograms/day whereas this release rate was 33 and 27 micrograms/day after 2 and 3 years, respectively. Although the in vitro set-up constantly gave a somewhat higher release in comparison with the in vivo release, it is apparent that the in vitro procedure is valuable for prediction of the in vivo release characteristics of the implant. There were no indications for 3-keto-desogestrel accumulation at the implantation site. No local irritations were seen and the animals had no discomfort at all.(ABSTRACT TRUNCATED AT 400 WORDS)