Pharmacokinetics of a 5-aminosalicylic acid enteric-coated tablet and suppository dosage form.
An Eudragit-L coated oral 5-aminosalicylic acid (5-ASA; mesalazine) product (Mesasal), has been formulated to deliver 5-ASA to the distal small intestine and colon for the treatment of inflammatory bowel disease. The purpose of this study was to compare the pharmacokinetic profile of this product to sulphasalazine (SASP; Salazopyrin) and to assess the pharmacokinetics of a suppository 5-ASA dosage form. Twelve healthy volunteers randomly received four single doses of 5-ASA delivering formulations not less than 1 week apart. (a) Mesasal tablets, 2 x 250 mg, fasting; (b) Mesasal tablets, 2 x 250 mg, fed; (c) Salazopyrin tablets, 3 x 500 mg (corresponding to 576 mg 5-ASA), fasting; and (d) Mesasal suppository, 1 x 500 mg, fasting. Plasma 5-ASA and acetyl-5-ASA (Ac-5-ASA) concentrations were followed for 48 h and urine and faecal concentrations for 72 h. Mesasal tablets (fasting) produced a greater area under the concentration-time curve (AUC), peak and time to peak for both plasma 5-ASA and Ac-5-ASA than Salazopyrin. Median urinary recovery values were 21.7% for Salazopyrin and 35.5% for Mesasal (fasting) (P less than 0.01). This means that the systemic absorption was higher after Mesasal than after Salazopyrin. The total faecal recovery values were 38.3 and 26.5%, respectively (NS). Except for a delay of 1.5-.3 h in the time to peak of 5-ASA and Ac-5-ASA plasma levels, the pharmacokinetics of Mesasal tablets were essentially the same in fasting or fed subjects. Suppository administration of 5-ASA resulted in a low median urinary recovery of 10.8%.
Norlander
B
B
Department of Clinical Pharmacology, University Hospital, Linköping, Sweden.
Gotthard
R
R
Ström
M
M
D000328:Adult; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D019804:Mesalamine; D013050:Spectrometry, Fluorescence; D013488:Suppositories; D013608:Tablets, Enteric-Coated
D000636:Aminosalicylic Acids; D013488:Suppositories; D013608:Tablets, Enteric-Coated; D019804:Mesalamine; C028836:N-acetyl-5-aminosalicylic acid