Wenzl R, van Beek A, Schnabel P, Huber J
University of Vienna, General Hospital, Department of Obstetrics and Gynecology, Austria.
Contraception. 1998 Nov;58(5):283-8. doi: 10.1016/s0010-7824(98)00110-3.
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.
8名年龄在22至40岁之间的健康女性参与了这项为期2年的前瞻性开放性研究。在自然月经周期的第1至7天内或当天，静脉推注150微克依托孕烯（3-酮去氧孕烯）。在随后自然周期的第1至5天，将单棒式避孕植入剂（依伴侬）植入志愿者的上臂。植入剂放置一年后，给予另一剂静脉推注（植入剂仍在位），2年后给予第三剂推注，并取出植入剂。在静脉注射依托孕烯后立即进行频繁的血清采样，以研究主要药代动力学参数，即分布容积和清除率，从而能够计算植入剂的吸收率和生物利用度随时间的变化情况。结果显示，依伴侬释放的依托孕烯在3个月后的吸收率约为60微克/天，在2年末缓慢降至30微克/天。在此时间段内生物利用度保持恒定且接近100%。清除率维持在7.5升/小时左右。鉴于生物利用度和清除率保持恒定，可以得出结论，依托孕烯不会蓄积。
