Metabolism studies on transdermal prostaglandin E1 in human foreskin in vitro.

The metabolism of prostaglandin E1 (PGE1) in solution and in transdermal liposomal formulations was investigated in vitro by incubation with homogenates from human foreskin (HSH), with rabbit lung (RLH) and human placenta (HPH) and heat denatured homogenates as controls, PGE1 and its metabolites and degradation products were analyzed by reversed phase HPLC. Metabolism of PGE1 in HSH was negligible up to 5 h whereas at 24 h, 83 +/- 1%, 92 +/- 2%, and 84 +/- 3% of the initial drug content remained from two different liposomal PGE1 and the free drug incubations, respectively. In HPH, 65 +/- 4% and 5 +/- 3% of initial PGE1 content remained, whereas in RLH, 73 +/- 2% and 60 +/- 3% PGE1 remained after 1 h and 24 h, respectively. The major metabolite was 15-ketoPGE1 in all homogenates. The specific 15-hydroxyprostaglandin dehydrogenase (15-OHPGDH) enzyme activities in HSH, RLH and HPH were found to be 0.22, 1.65, 5.29 nmol 15-ketoPGE1/h/mg homogenate protein, respectively. In conclusion, 15-OHPGDH activity was demonstrated in human foreskin. Encapsulation of PGE1 into liposomes can provide protection from skin metabolism. Based on our in vitro data, we predict that in vivo transdermal delivery of PGE1 is not limited by cutaneous metabolism.