Журнал биоэквивалентности и биодоступности

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Pharmacokinetics and Safety of a New 1200 mg Single-Dose Delayed Release Mesalazine Microgranule Formulation

Roda Aldo, Simoni Patrizia, Roda Giulia, Caponi Alessandra, Pastorini Elisabetta, Locatelli Marcello and Roda Enrico

The treatment of Inflammatory Bowel Diseases (IBDs) requires a relative high therapeutic daily dose of mesalazine and thus, the drug formulation need to b e well tolerate and safe. A new pH-dependent controlled release 5-ASA microgr anule formulation in 1.2 g sachets has been develop ed. The plasma levels of both the active principle 5-AS A and the main metabolite N-Acetyl-5-ASA, after ora l administration of the new formulation or after an e quimolar dose of three separated enteric coated 400 mg tablets administered in the same time (Pentacol® 40 0, SOFAR, Milan, ITALY), were measured with a valid ated high performance liquid chromatography-tandem mass spectrometry method. C max , t max and AUC values were considered as primary variables and the drug safety was the secondary one. The plasma 5-ASA concentration appearance was faste r after microgranule administration ( tmax of 8.1 hours) than after the reference tablets assumption (tmax o f 10.6 hours). The Cmax and AUC values were similar for both formulations and the kinetic of plasma disappe arance of the test formulation was slight faster. T he inter- subject variability was lower after administration of the microgranules with a %CV of 17.5% vs 40.4% f or the tablets (n=23), due to a more controlled homogeneo us drug release from the granule format. The N-Acet yl-5- ASA metabolite presents a similar plasma profile of the 5-ASA for both formulations. The use of microg ranules is safe and will allow to reduce the daily dosages, by improving the patients compliance also in prese nce of difficulty to swallow large tablets.