An Eudragit-coated prednisolone preparation for ulcerative colitis: pharmacokinetics and preliminary therapeutic use.
Prednisolone metasulphabenzoate, a steroid with poor colonic absorption, was coated with the pH-dependent acrylic resin Eudragit S, as a means of delivering an orally administered preparation to the proximal colon. The therapeutic potential of delivering this steroid with potentially less systemic side-effects to the proximal colon was assessed in extensive ulcerative colitis. Plasma and urine prednisolone profiles in 6 healthy volunteers confirmed minimal absorption from Eudragit S-coated prednisolone metasulphabenzoate compared to prednisolone acetate: peak plasma prednisolone concentrations 29 +/- 21 ng/ml vs. 570 +/- 185 ng/ml (P less than 0.01), area under curve measurements 204 +/- 214 vs. 2724 +/- 1236 ng.h/ml (P less than 0.01). Prednisolone metasulphabenzoate coated with Eudragit S (30-60 mg daily) was then administered for 12 weeks to 12 patients with colonoscopically proven extensive ulcerative colitis in relapse. Symptoms, sigmoidoscopic appearances and rectal histological abnormalities all improved during therapy. Complete clinical remission occurred in 7 patients, a partial response in 2 patients and no response in 3 patients. Cortisol responses to tetracosactrin demonstrated no significant adrenal suppression following treatment. Eudragit S-coated prednisolone metasulphabenzoate may be a useful treatment for extensive ulcerative colitis, without risk of systemic steroid side-effects.
Ford
G A
GA
Department of Medicine, Gloucestershire Royal Hospital, UK.
Oliver
P S
PS
Shepherd
N A
NA
Wilkinson
S P
SP
D000180:Acrylic Resins; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D011109:Polymethacrylic Acids; D011239:Prednisolone / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011863:Radioimmunoassay
D000180:Acrylic Resins; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C009935:prednisolone acetate; D011239:Prednisolone