Effects of salicylate and other enhancers on rectal absorption of erythropoietin in rats.
To develop a new treatment for patients with anaemia in which erythropoietin (EPO) can be given without injection, the effects of promoters of the rectal absorption of EPO were studied. Recombinant human (rHu) EPO (5000 units) in a dosing solution or in a rectal suppository was placed in the rectum of healthy rats and changes in serum EPO levels were monitored by an enzyme-linked immunosorbent assay. Without a promoter, rHuEPO was not absorbed. Sodium glycocholate, sodium caprate, and sodium salicylate in the solution of rHuEPO increased the absorption of rHuEPO. Sodium salicylate or sodium caprate in the suppository with rHuEPO also increased its absorption. The bioavailability of rHuEPO in a suppository containing 5% sodium salicylate compared with that by an intravenous injection was 1.2%. rHuEPO given in rectal suppositories containing sodium salicylate and inserted once a day for 6 consecutive days increased erythropoiesis in peripheral blood.
Research Institute of Life Science, Snow Brand Milk Products Co. Ltd, Tochigi, Japan.
A
A
Mizuno
M
M
Ueda
G
G
Kawanishi
D000285:Administration, Rectal; D000818:Animals; D001682:Biological Availability; D001729:Bismuth / Q000494:pharmacology*; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum / Q000187:drug effects / Q000378:metabolism*; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid; D013268:Stimulation, Chemical
D012459:Salicylates; D004921:Erythropoietin; D008274:Magnesium; D020156:Salicylic Acid; D001729:Bismuth