Forty-two healthy women volunteered to have blood samples drawn at 2, 4, 8, 24, 48, and 168 h (7 days) following placement of levonorgestrel-releasing rod (LNG rod) or of Norplant capsule implants to permit measurement of drug concentrations. Three clinics recruited 10 women each, half of whom used each type of implant. Twelve additional subjects were later enrolled at one site to provide greater detail for the capsule implants. Throughout the week, women with Norplant implants had apparently higher mean drug concentrations than did women with LNG rod implants, but the differences were significant only in the first 48 h after placement (p < 0.05). Maximum levels for capsule implants were found at the 24-h sample (mean, 1358 to 1474 pg/mL) and for the LNG rod implants at 48 h (772 pg/mL). Body weight was negatively correlated with levonorgestrel concentrations at all times (p < 0.05). For several sampling times, differences between clinics in mean concentrations were statistically significant after weight adjustment. Despite differences by implant type, weight, or clinic location, drug concentrations compatible with contraceptive effect were attained within 24 h in users of LNG rod or of Norplant implants, insofar as all women had levonorgestrel concentrations above 250 pg/mL at the 24-h sample.
PIP: To establish the minimum times required for contraceptive implants to achieve serum concentrations compatible with contraceptive action, drug concentrations were measured in blood samples collected from 42 women at 2, 4, 8, 24, and 168 hours after implant insertion. 15 volunteers from three centers (US, Chile, and the Dominican Republic) were fitted with a levonorgestrel (LNG)-releasing rod and 27 received Norplant implants. An LNG concentration of 250 pg/ml and above was considered indicative of contraceptive action. By 8 hours, all Norplant subjects but only 40% of the LNG rod subjects had achieved this serum level. By 24 hours, however, all women in both groups had LNG concentrations above 250 pg/ml. The maximum mean LNG level was recorded in the 24-hour sample (1358 pg/ml) in the Norplant group and at 48 hours (772 pg/ml) in the LNG rod group. Consistent with earlier investigations, LNG concentrations demonstrated strong and significant negative correlations with body weight at all time points. The paucity of pregnancies recorded in large-scale clinical trials in the first month of use of contraceptive implants supports the rapid attainment of effective LNG concentrations. It remains unclear, however, precisely how late in the menstrual cycle implants can be inserted and still prevent follicular development or halt ovulation. Until more information is available, continuation of the policy of implant placement in the first few days after the onset of menstruation is recommended.