RÉSUMÉ
OBJECTIVE: To determine pharmacokinetic profiles of two times a day and three times a day dosage regimens of Endometrin, a micronized progesterone vaginal insert for luteal support in assisted reproductive technology, compared with a gel. DESIGN: A single-center, randomized, open-label, single-day, and multiple-day (5 days) parallel design pharmacokinetic study. SETTING: University clinical research unit. PATIENT(S): Three groups of six healthy subjects, ages 18 to 40 years. INTERVENTION(S): Endometrin vaginal inserts two times a day or three times a day, or gel daily. MAIN OUTCOME MEASURE(S): Pharmacokinetic profiles. RESULT(S): Progesterone serum concentrations increased rapidly following administration of Endometrin vaginal insert, producing higher peak concentrations (Cmax) and clearing faster than gel. On the single day of dosing, mean Cmax was 17.0+/-2.7 ng/mL in the two times a day group, 19.8+/-2.9 ng/mL in the three times a day group, and 6.82+/-1.69 ng/mL in the gel group. Endometrin treatments reached steady state within the first 2 days (24-36 hours), much more rapidly than the gel, which had not reached steady state by 5 days. At 5 days, the Endometrin treatments produced sustained progesterone concentrations exceeding 10 mg/mL across 24 hours. CONCLUSIONS: Endometrin vaginal inserts reached higher Cmax, produced greater systemic exposure (area under the curve 0-24), achieved steady state more rapidly, and cleared more rapidly after termination of therapy than the comparator.
Sujet(s)
Progestérone/administration et posologie , Progestérone/pharmacocinétique , Crèmes, mousses et gels vaginaux/administration et posologie , Crèmes, mousses et gels vaginaux/pharmacocinétique , Administration par voie vaginale , Adolescent , Adulte , Facteurs âges , Formes posologiques , Relation dose-effet des médicaments , Calendrier d'administration des médicaments , Femelle , Santé , Humains , Progestérone/sang , Reproduction/effets des médicaments et des substances chimiques , Reproduction/physiologie , Techniques de reproduction assistée , Facteurs temps , Jeune adulteRÉSUMÉ
Publication of the new US Public Health Service-sponsored Clinical Practice Guideline, Treating Tobacco Use and Dependence: 2008, coupled with the persistent prevalence of tobacco use in the reproductive-age population and the negative effect of tobacco on fertility, prompts an updated review of this topic, geared to those who treat infertility.