On the metabolism of prostaglandin E1 administered intravenously to human volunteers.
We have demonstrated recently the formation of a biologically active metabolite of prostaglandin (PG) E1, 13,14-dihydro-PGE1, during intravenous infusions of PGE1 in patients with peripheral arterial occlusive disease. We have now investigated the levels of the immediate precursor of 13,14-dihydro-PGE1, the biologically inactive 15-keto-13,14-dihydro-PGE1, during intravenous administration of 20 micrograms, 40 micrograms or 80 micrograms PGE1 over a period of 60 min to human volunteers. It was found that levels of 15-keto-13,14-dihydro-PGE1, but not those of PGE1 itself, increased in a dose-dependent manner. Thus, increased formation of 13,14-dihydro-PGE1 from 15-keto-13,14-dihydro-PGE1 with increasing doses of PGE1 can be expected to occur. It remains to be investigated, to which extent formation of small amounts of 13,14-dihydro-PGE1 during intravenous infusion of PGE1 could contribute to the therapeutic effects of PGE1 in patients with peripheral arterial occlusive disease.
Peskar
B A
BA
Department of Pharmacology and Toxicology, Ruhr-University of Bochum, Germany.
Cawello
W
W
Rogatti
W
W
Rudofsky
G
G
D000328:Adult; D000527:Alprostadil / Q000097:blood* / Q000493:pharmacokinetics; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male
C025087:15-keto-13,14-dihydroprostaglandin E2; D000527:Alprostadil; D015232:Dinoprostone