Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration

Separate crossover studies compared the bioavailability of oral vs. vaginal routes of administration for the Yuzpe (n=5) and levonorgestrel regimens (n =4) of emergency contraception. Twice the standard dose of the Yuzpe regimen (200 mu g of ethinyl estradiol, 1000 mu g of levonorgestrel) or the levonorgestrel regimen (1500 mu g of levonorgestrel) was self-administered vaginally. One week later, each subject received orally the standard dose of the assigned medication. Serial blood samples were collected over 24 h and assayed for levonorgestrel and ethinyl estradiol (for the Yuzpe regimen only). Paired t tests were used to compare oral vs. vaginal administration for maximum concentration (C-max), time to maximum concentration (T-max) and area under the curve over 24 h (AUC(0-24)). Relative bioavailability (vaginal/oral) was derived from AUC(0-24). Vaginal administration of double the standard dose of the Yuzpe regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=14.6 ng/mL, p=.038) and a later T-max (5.9 vs. 2.0 h, p=.066) for levonorgestrel, compared to oral administration. Corresponding ethinyl estradiol concentrations were higher (786 vs. 391 pg/mL, p=.039) and peaked later (4.0 vs. 1.9 hr, p=.154) with vaginal administration. Relative bioavailabilities for levonorgestrel and ethinyl estradiol were 58% and 175%, respectively. Similarly, vaginal administration of the levonorgestrel regimen resulted in a lower C-max (vaginal=5.4 vs. oral=15.2 ng/mL, p=.006) and a later T-max (7.4 vs. 1.3 h, p=.037) for levonorgestel, compared to oral administration. The relative bioavailability was 62%. Our preliminary data suggest that vaginal administration of these emergency contraception regimens appears to require at least three times the standard oral dose to achieve equivalent systemic levonorgestrel concentrations. (c) 2005 Elsevier Inc. All rights reserved.