Combined scintigraphic and pharmacokinetic investigation of enteric-coated mesalazine micropellets in healthy subjects.
BACKGROUND
There is a growing clinical trend to increase the daily dose of mesalazine, which leads to significant compliance issues associated with multiple dosings of current preparations.


OBJECTIVE
To examine the gastrointestinal performance and systemic exposure of a 1.5 g sachet (micropellets) mesalazine formulation, compared with three enteric-coated tablets (500 mg each, Claversal).


METHODS
A randomized, two-way, cross-over pharmacoscintigraphic (scintigraphy plus pharmacokinetics) study and a two-way, cross-over, pharmacokinetic-only study were performed in 24 healthy volunteers (12 subjects per investigation).


RESULTS
The relative bioavailability of mesalazine was 92% comparing micropellets with Claversal tablets, and the cumulative urine excretion was c. 26% for both preparations, suggesting comparable systemic exposure for the two types of preparation. In the majority of subjects, drug release from the micropellet formulation occurred predominantly in the terminal ileum and ascending colon. The Claversal tablets disintegrated in comparable intestinal sites, albeit at slightly later time points than the micropellets, principally due to slower gastric emptying for the single-unit formulation.


CONCLUSIONS
The 1.5 g micropellet formulation offers comparable delivery properties to the marketed tablets, but with greater convenience of dosing.
Wilding
I R
IR
Pharmaceutical Profiles Ltd, Ruddington, Nottingham, UK. iwilding@pharmprofiles.co.uk
Behrens
C
C
Tardif
S J
SJ
Wray
H
H
Bias
P
P
Albrecht
W
W
D000284:Administration, Oral; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D004064:Digestive System / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D019804:Mesalamine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008863:Microspheres; D011877:Radionuclide Imaging; D013608:Tablets, Enteric-Coated
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013608:Tablets, Enteric-Coated; D019804:Mesalamine