title: Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration.
abstract: 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 microg of ethinyl estradiol, 1000 microg of levonorgestrel) or the levonorgestrel regimen (1500 microg 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 (Cmax), time to maximum concentration (Tmax) and area under the curve over 24 h (AUC0-24). Relative bioavailability (vaginal/oral) was derived from AUC0-24. 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 Tmax (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 Cmax (vaginal=5.4 vs. oral=15.2 ng/mL, p=.006) and a later Tmax (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.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology Victory 4, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada K7L 2V7.
authors.forename: Sari
authors.initials: S
authors.lastname: Kives
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hahn
authors.forename: Emily
authors.initials: E
authors.lastname: White
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: Robert L
authors.initials: RL
authors.lastname: Reid
mesh_terms: D000282:Administration, Intravaginal; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D003267:Contraception / Q000379:methods*; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004632:Emergency Medical Services; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010865:Pilot Projects; D011863:Radioimmunoassay; D016896:Treatment Outcome
chemical_list: D003271:Contraceptive Agents, Female; D004997:Ethinyl Estradiol; D016912:Levonorgestrel