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 μg of ethinyl estradiol, 1000 μg of levonorgestrel) or the levonorgestrel regimen (1500 μg 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 C max (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.