Brief Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Sep 14, 2013; 19(34): 5665-5670
Published online Sep 14, 2013. doi: 10.3748/wjg.v19.i34.5665
5-ASA colonic mucosal concentrations resulting from different pharmaceutical formulations in ulcerative colitis
Renata D’Incà, Martina Paccagnella, Romilda Cardin, Surajit Pathak, Vincenzo Baldo, Maria Cecilia Giron, Giacomo Carlo Sturniolo
Renata D’Incà, Martina Paccagnella, Romilda Cardin, Surajit Pathak, Giacomo Carlo Sturniolo, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, 35127 Padova, Italy
Vincenzo Baldo, Department of Environmental Medicine and Public Health, Institute of Hygiene, University of Padua, 35127 Padova, Italy
Maria Cecilia Giron, Department of Pharmacology and Anaesthesiology, University of Florence, 50121 Florence, Italy
Author contributions: D’Incà R co-ordinated the study and wrote the manuscript; Paccagnella M collected the human material and made the first draft of the manuscript; Cardin R performed the majority of the experiments; Pathak S revised the paper; Baldo V analysed the data; Giron MC provided criticisms and suggestions; Sturniolo GC designed the study.
Correspondence to: Dr. Renata D’Incà, Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, VI piano Monoblocco, Via Giustiniani 2, 35127 Padova, Italy. dinca@unipd.it
Telephone: +39-49-8212893 Fax: +39-49-8760820
Received: February 22, 2013
Revised: May 9, 2013
Accepted: May 18, 2013
Published online: September 14, 2013
Processing time: 203 Days and 19.1 Hours
Abstract

AIM: To compare the mucosal concentrations of 5-aminosalicylic acid (5-ASA) resulting from different pharmaceutical formulations and analyse the influence of inflammation on the mucosal concentrations.

METHODS: The study included 130 inflammatory bowel disease (IBD) patients receiving 5-ASA as pH-dependent-release formulations (73 patients), time-dependent-release formulations (11 patients), or pro-drugs (18 patients). In addition, 28 patients were receiving topical treatment (2-4 g/d) with pH-dependent-release formulations. Endoscopic biopsies were obtained from the sigmoid region during the colonoscopy. The 5-ASA concentrations (ng/mg) were measured in tissue homogenates using high-pressure liquid chromatography with electrochemical detection. The t test and Mann-Whitney test, when appropriate, were used for statistical analysis.

RESULTS: Patients receiving pH-dependent-release formulations showed significantly higher mucosal concentrations of 5-ASA (51.75 ± 5.72 ng/mg) compared with patients receiving pro-drugs (33.35 ± 5.78 ng/mg, P = 0.01) or time-dependent-release formulations (38.24 ± 5.53 ng/mg, P = 0.04). Patients with endoscopic remission had significantly higher mucosal concentrations of 5-ASA than patients with active disease (60.14 ± 7.95 ng/mg vs 35.66 ± 5.68 ng/mg, P = 0.02). Similar results were obtained when we compared patients with the histological appearance of remission and patients with active histological inflammation (67.53 ± 9.22 ng/mg vs 35.53 ± 5.63 ng/mg, P < 0.001). Significantly higher mucosal concentrations of 5-ASA were detected in patients treated with both oral and topical treatments in combination compared with patients who received oral treatment with pH-dependent-release formulations alone (72.33 ± 11.23 ng/mg vs 51.75 ± 5.72 ng/mg, P = 0.03).

CONCLUSION: IBD patients showed significant variability in mucosal 5-ASA concentrations depending on the type of formulation, and the highest mean concentration was achieved using pH-dependent-release formulations.

Keywords: 5-aminosalicylic acid; Inflammatory bowel diseases; Mucosal concentration

Core tip: We report on the concentrations of 5-aminosalicylic acid in the colonic mucosa of ulcerative colitis patients. Significant variations in concentration were observed that were dependent on the type of pharmaceutical formulation and the presence of active disease. Combined oral and topical therapy yielded higher tissue mesalamine concentrations. These differences should be taken into account in treatment strategies, especially in view of the fact that mesalamine can induce mucosal healing in ulcerative colitis.