Zhang Chao, Li Haiyan, Xiong Xin, Zhai Suodi, Wei Yudong, Zhang Shuang, Zhang Yuanyuan, Xu Lin, Liu Li
Department of Pharmacy.
Institute of Clinical Trial, Peking University Third Hospital, Beijing, People's Republic of China.
Drug Des Devel Ther. 2017 Mar 10;11:725-731. doi: 10.2147/DDDT.S131123. eCollection 2017.
We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (), extended time to reach the and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration-time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations.
我们研究了一种新开发的炔雌醇（EE）/孕二烯酮（GSD）复方透皮避孕贴片单剂量给药后的药代动力学和安全性概况，并与市售片剂剂型在健康成年受试者中进行了比较。在12名健康女性志愿者中进行了一项开放标签、两阶段的对照研究。给予单剂量的研究用EE/GSD复方透皮避孕贴片和口服片剂（米非司酮）。在给药后的不同时间点采集血样，并分析浓度。本研究开发了一种可靠、高度灵敏且准确的高效液相色谱-串联质谱（HPLC/MS/MS）测定方法，以测定EE和GSD的血浆浓度。与片剂相比，研究用贴片的最大血浆浓度显著降低（），达到和半衰期的时间延长，清除率和表观分布容积增加。贴片中EE和GSD的半衰期分别是片剂半衰期的3.3倍和2.2倍。贴片中EE和GSD的血浆浓度-时间曲线下面积（AUC）分别是片剂AUC的8.0倍和16.2倍。在整个研究过程中未观察到严重不良事件，总体安全性可接受。总之，与口服片剂米非司酮相比，研究用避孕贴片耐受性良好，药物暴露量高，半衰期显著延长，药物浓度稳定。
