Gastrointestinal transit and release of 5-aminosalicylic acid from 153Sm-labelled mesalazine pellets vs. tablets in male healthy volunteers.
BACKGROUND
Mesalazine (5-aminosalicylic acid)-containing formulations, designed to optimize drug delivery to the ileo-caecal region, represent a cornerstone in the treatment of inflammatory bowel diseases.


OBJECTIVE
: To test, by means of pharmaco-scintigraphy, whether novel mesalazine-containing pellets release 5-aminosalicylic acid in the same target region as mesalazine tablets (Salofalk).


METHODS
Fourteen healthy male volunteers received a single dose of either pellets or tablets containing 500 mg of mesalazine and 2 mg of 152Sm2O3 with a 1-week washout period. The gastrointestinal transit of 153Sm, incorporated into the formulations, was followed by gamma-scintigraphy. Mesalazine release was verified by assessing 5-aminosalicylic acid plasma pharmacokinetics.


RESULTS
The formulations reached the ileo-caecal target region almost at the same time (3.3 +/- 1 and 3.8 +/- 1 h for pellets and tablets, respectively). Plasma 5-aminosalicylic acid tmax values were comparable and corresponded to the time during which the formulations were located in the target region. Plasma AUC values were significantly lower for pellets, which might be explained by a more prolonged release of 5-aminosalicylic acid.


CONCLUSIONS
Novel mesalazine pellets and Salofalk tablets release active 5-aminosalicylic acid in the same target region and pass through the gastrointestinal tract under fasting conditions in healthy volunteers in a comparable time. From a comparison of in vitro dissolution and plasma concentration data, a slower and more prolonged release of 5-aminosalicylic acid from pellets is suggested.
Brunner
M
M
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University of Vienna Medical School, Vienna, Austria. martin.brunner@univie.ac.at
Greinwald
R
R
Kletter
K
K
Kvaternik
H
H
Corrado
M E
ME
Eichler
H G
HG
Müller
M
M
D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D001692:Biological Transport; D002432:Cecum / Q000378:metabolism*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004343:Drug Implants / Q000008:administration & dosage; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D008297:Male; D019804:Mesalamine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013607:Tablets / Q000008:administration & dosage
D003692:Delayed-Action Preparations; D004343:Drug Implants; D013607:Tablets; D019804:Mesalamine