摘要：

The metabolism of prostaglandin E 1 (PGE 1 ) 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. PGE 1 and its metabolites and degradation products were analyzed by reversed phase HPLC. Metabolism of PGE 1 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 PGE 1 and the free drug incubations, respectively. In HPH, 65±4% and 5±3% of initial PGE 1 content remained, whereas in RLH, 73±2% and 60±3% PGE 1 remained after 1 h and 24 h, respectively. The major metabolite was 15-ketoPGE 1 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-ketoPGE 1 /h/mg homogenate protein, respectively. In conclusion, 15-OHPGDH activity was demonstrated in human foreskin. Encapsulation of PGE 1 into liposomes can provide protection from skin metabolism. Based on our in vitro data, we predict that in vivo transdermal delivery of PGE 1 is not limited by cutaneous metabolism.

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