Foldvari M, Oguejiofor C, Afridi S, Kudel T, Wilson T
College of Pharmacy and Nutrition, Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Urology. 1998 Nov;52(5):838-43. doi: 10.1016/s0090-4295(98)00299-4.
To test the delivery of prostaglandin E1 (PGE1) in novel transdermal liposomal formulations through foreskin and to determine whether there is a correlation between in vitro transdermal absorption and in vivo efficacy in patients with erectile dysfunction.
The in vitro transdermal absorption of PGE1 through excised foreskin from liposomal formulations was tested in diffusion cells using radiolabeled drug. The in vivo studies were carried out on 5 patients (aged 54 to 70 years) in a double-blind, placebo-controlled fashion. The patients were treated topically on the penis with three different active formulations containing 0.05% PGE1 and a placebo at least 1 week apart. The change in systolic peak flow velocities in the cavernosal arteries after treatment was monitored by duplex color Doppler ultrasonography with spectral analysis every 15 minutes for 1 hour.
The permeability coefficient (Kp) of PGE1 from the three liposomal formulations tested was found to be 0. 10, 1.66, and 3.82 x 10(-4) cm/hr, respectively. Peak systolic flow velocities in the deep cavernosal arteries of patients increased significantly compared with preapplication values (0.05 < P < or = 0.1) after application of two of the transdermal liposomal PGE1 formulations tested (the two with the highest Kp). The highest mean peak systolic flow velocity was achieved at 45 minutes after application of the formulations. The most effective formulation in this study resulted in a sevenfold increase in mean flow velocity compared with baseline values.
Topical application of PGE1 in a novel transdermal liposomal delivery system can enhance penetration of the drug into the deep cavernosal bodies and increase peak systolic flow velocities in patients with erectile dysfunction. The transdermal flux and permeability of PGE1 measured in vitro correlate well with the color Doppler ultrasound results in patients. The efficacy of a formulation in the development process may be predicted from in vitro absorption studies.
测试新型经皮脂质体制剂中前列腺素E1（PGE1）透过包皮的递送情况，并确定勃起功能障碍患者的体外经皮吸收与体内疗效之间是否存在相关性。
使用放射性标记药物，在扩散池中测试PGE1从脂质体制剂透过切除的包皮的体外经皮吸收。对5名患者（年龄54至70岁）进行双盲、安慰剂对照的体内研究。患者阴茎局部使用三种不同的活性制剂，每种制剂含0.05% PGE1，且至少间隔1周使用一次安慰剂。治疗后，每15分钟用双功彩色多普勒超声和频谱分析监测海绵体动脉收缩期峰值流速变化，持续1小时。
测试的三种脂质体制剂中PGE1的渗透系数（Kp）分别为0.10、1.66和3.82×10⁻⁴ cm/hr。测试的两种经皮脂质体PGE1制剂（Kp最高的两种）应用后，患者海绵体深动脉的收缩期峰值流速较应用前显著增加（0.05 < P ≤ 0.1）。制剂应用后45分钟达到最高平均收缩期峰值流速。本研究中最有效的制剂使平均流速较基线值增加了7倍。
在新型经皮脂质体递送系统中局部应用PGE1可增强药物渗透至海绵体深部，并增加勃起功能障碍患者的收缩期峰值流速。体外测得的PGE1经皮通量和渗透率与患者的彩色多普勒超声结果相关性良好。开发过程中制剂的疗效可通过体外吸收研究进行预测
