周效避孕用复方依托孕烯透皮贴剂的家兔体内药物动力学和药效学评价

以丙烯酸酯压敏胶为黏合基质,采用透皮控释技术制备周效依托孕烯和炔雌醇的复方避孕贴剂.采用LC-MS/MS法测定家兔血浆中炔雌醇和依托孕烯的浓度,并考察其对家兔抗排卵的效果.结果表明,复方依托孕烯贴剂贴于家兔腹部透皮给药7d,能维持较恒定的血药浓度,移除贴剂后,血药浓度迅速降低.家兔抗排卵试验结果显示,给药1 d后,复方依托孕烯贴剂对家兔交配诱发排卵有明显的抑制作用,平均排卵点为0.60±1.3,与空白对照组平均排卵点6.0±1.9相比,其排卵抑制率为90.0%;给药7 d后,对家兔交配诱发排卵也有明显的抑制作用,平均排卵点为1.25±1.5,与相应的空白对照组平均排卵点4.5±1.0相比,排卵抑制率为72.2%.表明复方依托孕烯贴剂具有显著的抗排卵作用.

Pharmacokinetical and Pharmacodynamical Evaluation in Rabbits for Once-weekly Contraception of Compound Etonogestrel and Ethinyl Estradiol Transdermal Delivery System

The once-weekly compound etonogestrel (ET) and ethinly estradiol (EE) transdermal contraceptive patch was prepared with acrylic adhesive. The plasma concentration of EE and ET were determined by LC-MS/MS and the effects of ovulation inhibition of the patch in rabbits were evaluated. The steady plasma concentration in rabbits maintained for 7 days, but decreased rapidly after the patch was removed. The results of ovulation inhibition tests showed that the ovulation could be restrained after one day's deliverey of the patch, and the ovulation inhibition rate was 90.0% compared with the control group. And after seven days' delivery, the ovulation inhibition rate was 72.2%. The results showed that the compound enotogestrel and ethinly estradiol transdermal system could maintain the drug release through rabbit skin for at least 7days and achieve the intention of once-weekly contraception.