Liposome encapsulated prostaglandin E1 in erectile dysfunction: correlation
between in vitro delivery through foreskin and efficacy in patients.
Author(s): Foldvari M, Oguejiofor C, Afridi S, Kudel T, Wilson T.
Affiliation(s): College of Pharmacy and Nutrition, Department of Surgery, College of Medicine,
University of Saskatchewan, Saskatoon, Canada.
Publication date & source: 1998, Urology. , 52(5):838-43
OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
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