Pharmaceutical characterization of corticosteroid suppository treatment for ulcerative colitis.
The dose and method of administration of a corticosteroid given for the treatment of patients with ulcerative colitis are determined according to the range of the diseased area and its severity. In this study, we prepared a hydrophilic suppository consisting of water-soluble prednisolone sodium succinate (PSL-SS) and a hydrophilic base, polyethylene glycol (PEG), and a hydrophobic suppository consisting of water-insoluble prednisolone (PSL) and a hydrophobic base, Witepsol (WT). We determined the spread of the drugs after intrarectal administration and their therapeutic effect. When rats received the hydrophilic suppository, the drug spread farther oral than when they received the hydrophobic suppository. Moreover, more than half of the PSL-SS recovered was observed to have changed into PSL. A therapeutic effect on the colitis induced in rats by acetic acid was noted in the area up to 10 cm from the anus in the case of the hydrophilic suppository, while the effect of the hydrophobic suppository was seen only in the area up to 2.5 cm from the anus. In patients with ulcerative colitis, the hydrophilic suppository showed retrograde spread to a site 34.4 +/- 5.3 cm from the anus, while the hydrophobic suppository spread to a site 19.0 +/- 2.4 cm from the anus. These results suggest that a hydrophobic suppository should be used for patients in whom inflammation is confined to the rectum, and a hydrophilic suppository used for patients in whom inflammation reaches the rectum and the middle part of the sigmoid colon.
Sadahiro
S
S
Department of Surgery, Kawasaki City Ida Hospital, Japan.
Ito
Z
Z
Iijima
T
T
Noguchi
M
M
Hosoi
K
K
D000284:Administration, Oral; D000818:Animals; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004304:Dosage Forms; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D011092:Polyethylene Glycols; D011239:Prednisolone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000378:metabolism; D012995:Solubility; D013488:Suppositories; D014280:Triglycerides
D004304:Dosage Forms; D013488:Suppositories; D014280:Triglycerides; C009683:witepsol; D011092:Polyethylene Glycols; D011239:Prednisolone