Pharmacokinetics and endometrial tissue levels of levonorgestrel after administration of a single 1.5-mg dose by the oral and vaginal route

To determine the pharmacokinetics and endometrial tissue levels of levonorgestrel when taken as a single dose of 1.5 mg either orally or vaginally by healthy women in the periovulatory phase of their menstrual cycle. Prospective randomized study. Academic research institution. Thirty women with regular cycles allocated to control (n = 5), oral (n = 13), and vaginal (n = 12) groups. Blood samples were drawn before (0 time) and at 0.5, 1, 2, 4, 6, 8, 24, 48, and 168 hours after levonorgestrel administration. Endometrial samples were collected 24 and 168 hours after levonorgestrel administration. Plasma and endometrial tissue levels of levonorgestrel. Plasma concentrations of levonorgestrel were significantly greater during the first 48 hours after oral administration. However, 7 days after levonorgestrel administration, the plasma levels were similar for both treatments (3–5 nmol/L). Compared with vaginal administration, oral administration resulted in higher peak plasma concentrations (C max 64 vs. 10.7 nmol/L), with a shorter time to reach the maximal concentrations (T max 1.4 vs. 6.6 hours) and with a greater AUC (509 vs. 175 nmol/L). Interestingly, the half-life of levonorgestrel was shorter after oral administration (25 hours vs. 32.6 hours). Levonorgestrel tissue concentrations were not related to the plasma levels. Levonorgestrel values tended to be higher in endometrial tissue after vaginal administration. The ratio between plasma and endometrial concentrations of levonorgestrel differed significantly between the groups. These data indicate that orally administered levonorgestrel achieves higher plasma levels sooner than vaginally administered levonorgestrel. However, plasma levels after vaginal administration are more sustained and were likely to be sufficient for ovarian suppression. Therefore, the vaginally administered levonorgestrel could be considered as an alternative option for emergency contraception.