Ding Wu-Xiao, Qi Xian-Rong, Fu Qiang, Piao Hui-Shan
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Drug Deliv. 2007 Feb;14(2):101-4. doi: 10.1080/10717540600740102.
For emergency contraceptive, the rapid delivery of levonorgestrel (LNG) to plasma is desirable, furthermore, a sustained delivery of LNG along with rapid absorption will be necessary. The pharmacokinetics and pharmacodynamics of LNG entrapped in different kinds of liposome formulations via nasal administration in rats were evaluated and compared with LNG suspension via the oral route. The relative bioavailabilities of these liposome formulations via nasal administration were 100% or higher than 100%. The Cmax and Tmax values of sterylglucoside (SG) and chitosan-contained formulations by nasal administration were 416.84 ng/mL and 1.02 hr, 227.97 ng/mL and 2.02 hr, respectively, compared with that of 334.94 ng/mL and 1.89 hr of oral suspension. Fully 100% contraception was observed for all the formulations. SG could promote the absorption of LNG via the nasal route and may provide a rapid onset of action of LNG for emergency contraception. Chitosan could retain LNG in the nasal cavity for long contact time to sustain delivery of LNG. The rapid onset and sustained delivery of LNG can be achieved via the nasal route using liposomes as the vehicle.
对于紧急避孕药而言，希望左炔诺孕酮（LNG）能迅速释放到血浆中，此外，LNG在快速吸收的同时还需要持续释放。评估了不同类型脂质体制剂经鼻腔给药在大鼠体内的LNG药代动力学和药效学，并与口服途径的LNG混悬液进行了比较。这些脂质体制剂经鼻腔给药的相对生物利用度为100%或高于100%。经鼻腔给药的含甾醇糖苷（SG）和壳聚糖制剂的Cmax和Tmax值分别为416.84 ng/mL和1.02小时、227.97 ng/mL和2.02小时，而口服混悬液的Cmax和Tmax值分别为334.94 ng/mL和1.89小时。所有制剂均观察到100%的避孕效果。SG可促进LNG经鼻腔吸收，并可能为紧急避孕提供LNG的快速起效作用。壳聚糖可使LNG在鼻腔中长时间滞留，以维持LNG的递送。使用脂质体作为载体经鼻腔途径可实现LNG的快速起效和持续递送。
