Release Of 5-ASA Research Articles

Carboxymethyl cellulose-rosin gum hybrid nanoparticles: An efficient drug carrier

Adequate release of 5-ASA in colon is challenging as it easily permeates at the acidic pH of the upper gastrointestinal tract. Targeting delayed release of 5-ASA at acidic pH, Carboxymethyl cellulose-rosin gum hybrid nanoparticles (CRNP3) with an average size of 267nm have been crafted through nanoprecipitation method. CRNP3 was extensively characterized using Fourier Transform Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and particle size analysis based on dynamic light scattering. Colon specific targeted in-vitro release of 5‑Aminosalicylic acid from CRNPs was monitored in simulated gastric (SGF) and intestinal (SIF) fluids. The release rate was very slow in first 2h in SGF, while in SIF, it was greater and 72% drug was released in a controlled manner during the time span of 12h in contrast to native carboxymethyl cellulose or rosin gum for which 100% release was accomplished within 5h or 8h respectively. The delayed release from CRNPs is attractive for enhancing the bioavailability of drug in colon. The drug release followed zero-order kinetics and non-Fickian diffusion mechanism.

Novel levan and pNIPA temperature sensitive hydrogels for 5-ASA controlled release

Levan based cross-linker was successfully synthesized and used to prepare a series of more biocompatible and temperature responsive levan/N-isopropyl acrylamide (levan/pNIPA) hydrogels by redox polymerization at room temperature. Volume phase transition temperature (VPTT) of the hydrogels were precisely determined by derivative differential scanning calorimetry (DDSC). Incorporation of levan into the pNIPA hydrogel increased the VPTT from 32.8°C to 35.09°C, approaching to body temperature. Swelling behavior and 5-aminosalicylic acid (5-ASA) release of the hydrogels were found to vary significantly with temperature and composition. Moreover, a remarkable increase in thermal stability of levan within hydrogel with increase of pNIPA content was recorded. The biocompatibility of the hydrogels were tested against mouse fibroblast L929 cell line in phosphate buffer saline (PBS, pH 7.4). The hydrogels showed increasing biocompatibility with increasing levan ratio, indicating levan enhanced the hydrogel surface during swelling.

Obtaining the palygorskite:chitosan composite for modified release of 5-aminosalicylic acid

This study's aim was to obtain composites from palygorskite (PLG) and chitosan (CS) in order to modify 5-aminosalicylic (5-ASA) release. Initially, the PLG:CS composite was obtained using glutaraldehyde (GLA) as a reticular agent. Then, PLG, CS and PLG:CS were characterized by means of analytical techniques such as CHN elemental analysis, surface area analysis, XRD, FTIR, DSC and TG, SEM, adsorption tests and release profiles. Based on analytical data, the formation of the PLG:CS composite which showed the presence about 19% of CS, decrease in specific surface area, morphological analysis modified, visible change of crystallinity, of FTIR and thermal analysis. In relation to the drug-composite interaction, PLG:CS exhibited a significant increase in adsorption with 5-ASA at 58.24% in relation to PLG and CS which were at 16.29% and 23.96% respectively. The release profiles show that the PLG:CS composite changed the 5-ASA release speed in analyzed simulated fluids (intestinal and stomach) unlike other systems. Thus, the PLG:CS composite with proven synergy of the PLG and CS inherent properties showing 5-ASA effective modified release. Hence, this composite has potential benefits for the vectorization of drugs.

Construction of pH-responsive and up-conversion luminescent NaYF₄:Yb³⁺/Er³⁺@SiO₂@PMAA nanocomposite for colon targeted drug delivery.

Colon-targeted drug delivery system has attracted much interest because it can improve therapeutic efficacy and reduce the side effect in practical clinic. Herein, we constructed a multifunctional drug delivery system with colonic targeting and tracking by up-conversion (UC) luminescence based on core-shell structured NaYF4:Yb3+/Er3+@SiO2@PMAA nanocomposite. The resultant materials exhibited bright UC luminescence, pH-responsive property and excellent biocompatibility. The drug release behaviors in different pH environment were investigated using 5-aminosalicylic acid (5-ASA) as a model drug. The 5-ASA molecules release from NaYF4:Yb3+/Er3+@SiO2@PMAA nanocomposite exhibit a significant pH-responsive colon targeted property, i.e., a little amount of drug release in simulated gastric fluid (SGF, pH = 1.2) but a large amount of drug release in simulated colonic fluid (SCF, pH = 7.4) Moreover, the drug release process could be monitored by the change of UC emission intensity. These results implied that the multifunctional nanocomposite is a promising drug carrier for targeted release of 5-ASA in the colon.

Dissolution of Commercially Available Mesalamine Formulations at Various pH Levels.

IntroductionMesalamine (5-aminosalicylic acid; 5-ASA) is recommended first-line therapy for mild-to-moderate ulcerative colitis. Many mesalamine formulations employ a pH-dependent release mechanism designed to maximize drug release in the colon. This study compared the in vitro release of 5-ASA from six commercially available mesalamine formulations at pH levels similar to those typically encountered in the human gastrointestinal tract.MethodsThe release of 5-ASA from six mesalamine formulations [Mesalazin-Kohlpharma (Kohlpharma, Germany), Mesalazin-Eurim (Eurimpharm, Germany), Mesalazina-Faes (Faes Farma, Spain), Mesalazine EC (Actavis B.V., Netherlands), Mesalazine EC 500 PCH (Pharmachemie B.V., Netherlands); multimatrix mesalamine (Shire US Inc., USA)] was monitored separately at three different pH levels [1.0 (2 h), 6.4 (1 h), and 7.2 (8 h)] using United States Pharmacopeia dissolution apparatus II. The dissolution percentage was calculated as a mean of 12 units for each formulation.ResultsAt pH 1.0 and 6.4, <1 % of 5-ASA release was observed for each of the mesalamine formulations tested. At pH 7.2, complete release of 5-ASA occurred within 1 h for Mesalazine EC and Mesalazine EC 500 PCH, and within 2 h for Mesalazin-Kohlpharma, Mesalazin-Eurim, and Mesalazina-Faes; complete release of 5-ASA from multimatrix mesalamine occurred within 7 h. Little variability in rate of 5-ASA dissolution was observed between tablets of each formulation.ConclusionAt pH 7.2, 5-ASA release profiles were variable among the commercially available mesalamine formulations that were tested.

Release of 5-Aminosalicylic Acid (5-ASA) from Mesalamine Formulations at Various pH Levels.

IntroductionOral formulations of 5-aminosalicylic acid (5-ASA) for treatment of ulcerative colitis have been developed to minimize absorption prior to the drug reaching the colon. In this study, we investigate the release of 5-ASA from available oral mesalamine formulations in physiologically relevant pH conditions.MethodsRelease of 5-ASA from 6 mesalamine formulations (APRISO®, Salix Pharmaceuticals, Inc., USA; ASACOL® MR, Procter & Gamble Pharmaceuticals UK Ltd.; ASACOL® HD, Procter & Gamble Pharmaceuticals, USA; MEZAVANT XL®, Shire US Inc.; PENTASA®, Ferring Pharmaceuticals, Ltd., UK; SALOFALK®, Dr. Falk Pharma UK Ltd.) was evaluated using United States Pharmacopeia apparatus I and II at pH values of 1.0 (2 h), 6.0 (1 h), and 6.8 (8 h). Dissolution profiles were determined for each formulation, respectively.ResultsOf the tested formulations, only the PENTASA formulation demonstrated release of 5-ASA at pH 1.0 (48%), with 56% cumulative release after exposure to pH 6.0 and 92% 5-ASA release after 6–8 h at pH 6.8. No other mesalamine formulation showed >1% drug release at pH 1.0. The APRISO formulation revealed 36% 5-ASA release at pH 6.0, with 100% release after 3 h at pH 6.8. The SALOFALK formulation revealed 11% 5-ASA release at pH 6.0, with 100% release after 1 h at pH 6.8. No 5-ASA was released by the ASACOL MR, ASACOL HD, and MEZAVANT XL formulations at pH 6.0. At pH 6.8, the ASACOL MR and ASACOL HD formulations exhibited complete release of 5-ASA after 4 and 2 h, respectively, and the MEZAVANT XL formulation demonstrated complete 5-ASA release over 6–7 h.Conclusion5-Aminosalicylic acid release profiles were variable among various commercially available formulations.FundingShire Development LLC.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0206-4) contains supplementary material, which is available to authorized users.

Mo1225 Factors Associated With C. difficile Negative Gastrointestinal Symptoms After Intestinal Microbiome Restoration

5-ASA levels increased after 1 h for Pentasa and Apriso and 3 h for Lialda. Prominent 5ASA and Ac-5-ASA release after Pentasa was observed at all GI sites (including gastric). Gastric 5-ASA levels were >170-fold higher after Pentasa vs. Lialda. Peak small bowel GI 5-ASA (Figure 1) and Ac-5-ASA (not shown) levels were 15 to 1000+ fold lower for Lialda vs. Pentasa and Apriso, emphasizing greater colon release for Lialda. In addition, peak GI Ac-5-ASA levels were seen earlier with Pentasa (4.0+2.0 h) vs. Apriso (7.0+0.0 h) and Lialda (6.0+1.4 h). Plasma 5-ASA and Ac-5-ASA levels were lower vs. GI fluids consistent with luminal actions (Table 1). As in GI fluids, plasma 5-ASA and Ac-5-ASA appeared earliest for Pentasa and latest for Lialda. Peak plasma levels occurred 12 h after Lialda, reflecting again mostly colon absorption. Conclusions: Using novel multiport catheters to aspirate GI fluids for regional drug release analysis, we showed variable time-dependent appearance and absorption of 3 mesalamine products. Release of 5-ASA and its metabolite occurred earliest and most proximally with Pentasa (including gastric release). Small bowel release and absorption were slower and more distal with Apriso and were minimal with Lialda. Such innovative in vivo techniques will be used to validate in vitro dissolution methods and support computational models for future processes that are applicable to developing luminally-acting and extended-release drugs. This research was funded by FDA grants HHSF223201000082C and HHSF223201300460A.

Mo1227 Cathelicidin Mimic Ceragenin CSA13 Modulates Clostridium difficile Associated Colitis and Toxin a Mediated Enteritis in Mice

5-ASA levels increased after 1 h for Pentasa and Apriso and 3 h for Lialda. Prominent 5ASA and Ac-5-ASA release after Pentasa was observed at all GI sites (including gastric). Gastric 5-ASA levels were >170-fold higher after Pentasa vs. Lialda. Peak small bowel GI 5-ASA (Figure 1) and Ac-5-ASA (not shown) levels were 15 to 1000+ fold lower for Lialda vs. Pentasa and Apriso, emphasizing greater colon release for Lialda. In addition, peak GI Ac-5-ASA levels were seen earlier with Pentasa (4.0+2.0 h) vs. Apriso (7.0+0.0 h) and Lialda (6.0+1.4 h). Plasma 5-ASA and Ac-5-ASA levels were lower vs. GI fluids consistent with luminal actions (Table 1). As in GI fluids, plasma 5-ASA and Ac-5-ASA appeared earliest for Pentasa and latest for Lialda. Peak plasma levels occurred 12 h after Lialda, reflecting again mostly colon absorption. Conclusions: Using novel multiport catheters to aspirate GI fluids for regional drug release analysis, we showed variable time-dependent appearance and absorption of 3 mesalamine products. Release of 5-ASA and its metabolite occurred earliest and most proximally with Pentasa (including gastric release). Small bowel release and absorption were slower and more distal with Apriso and were minimal with Lialda. Such innovative in vivo techniques will be used to validate in vitro dissolution methods and support computational models for future processes that are applicable to developing luminally-acting and extended-release drugs. This research was funded by FDA grants HHSF223201000082C and HHSF223201300460A.

Modified hydroxypropyl methyl cellulose: Efficient matrix for controlled release of 5-amino salicylic acid

Hydroxypropyl methyl cellulose has been modified by grafting synthetic polyacrylamide chains [g-HPMC (M)] in presence of microwave irradiation, which has used as carrier for controlled release of 5-amino salicylic acid (5-ASA). The FTIR and UV–vis–NIR studies reveal the excellent compatibility between g-HPMC (M) and 5-ASA. Field emission scanning electron microscopy (FESEM) and UV–vis–NIR analyses suggest that physical interaction predominates between the drug and matrix. % equilibrium swelling ratio (% ESR) of g-HPMC (M) decreased with addition of salt solutions and follow the order: Na+>K+>Mg2+>Ca2+>Al3+. The in vitro 5-ASA release studies indicate that g-HPMC (M) delivers the drug preferentially in colonic region in more sustained way than that of HPMC. The 5-ASA release follows first order kinetics and non-Fickian diffusion mechanism. These favorable features make the graft copolymer a potential matrix for colon specific delivery of 5-ASA.

Synthesis and applications of polyacrylamide grafted agar as a matrix for controlled drug release of 5-ASA

Agar has been modified by microwave assisted grafting with acrylamide monomer, resulting in poly acrylamide grafted agar (Ag-g-PAM). The synthesized grades of Ag-g-PAM were characterized by standard physico-chemical characterization techniques (FTIR spectroscopy, elemental analysis, scanning electron microscopy (SEM)) to ascertain the intended grafting. The synthesized graft copolymer (Ag-g-PAM) has been investigated (in vitro) for controlled and colon targeted release of 5-amino salicylic acid (5-ASA).

Synthesis and Evaluation of a Nanoglobular Dendrimer 5-Aminosalicylic Acid Conjugate with a Hydrolyzable Schiff Base Spacer for Treating Retinal Degeneration

Biocompatible dendrimers with well-defined nanosizes are increasingly being used as carriers for drug delivery. 5-Aminosalicylic acid (5-ASA) is an FDA-approved therapeutic agent recently found effective in treating retinal degeneration of animal models. Here, a water-soluble dendrimer conjugate of 5-ASA (AGFB-ASA) was designed to treat such retinal degeneration. The drug was conjugated to a generation 2 (G2) lysine dendrimer with a silsesquioxane core (nanoglobule) by using a hydrolyzable Schiff base spacer. Incubation of nanoglobular G2 dendrimer conjugates containing a 4-formylbenzoate (FB) Schiff base spacer in pH 7.4 phosphate buffers at 37 °C gradually released 5-ASA. Drug release from the dendrimer conjugate was significantly slower than from the low molecular weight free Schiff base of 5-ASA (FB-ASA). 5-ASA release from the dendrimer conjugate was dependent on steric hindrance around the spacer. After intraperitoneal injection, the nanoglobular 5-ASA conjugate provided more effective 7-day protection against light-induced retinal degeneration at a reduced dose than free 5-ASA in Abca4(-/-)Rdh8(-/-) mice. The dendrimer 5-ASA conjugate with a degradable spacer could be a good candidate for controlled delivery of 5-ASA to the eye for treatment of retinal degeneration.

Preparation and properties of a pH sensitive carrier based on three kinds of polymer blend to control the release of 5-amino salicylic acid

Context: High concentration of 5-amino salicylic acid (5-ASA) in the distal ileum and colon is necessary for the treatment of inflammatory bowel disease (IBD). The control of small molecules, drugs, released from a polymeric matrix remains a great challenge.Objective: To study the preparation and properties of a pH-sensitive carrier for targeting delivery of 5-ASA.Materials and methods: The carrier was prepared by ternary blends method based on polyvinyl alcohol (PVA), sodium alginate (SA) and polylactic acid. It was characterized by infrared spectrometry and scanning electronic microscopy. The adsorption and release of 5-ASA in different pH media were investigated.Results: We found out the best ratio of the materials for synthetic carrier. The vector exhibited good performance by the controlled release of the target drug experiment. The adsorption capacity of the carrier for 5-ASA was 70.34% in phosphate buffer saline at pH 1.00, and the release rate was 100.49% in phosphate buffer solution at pH 6.80.Discussion and conclusion: PVA is vector backbone of the carrier, and SA plays key role in its pH performance. It is a promising material to effectively deliver 5-ASA to the specific sites of IBD.

In vitro digestion and fermentation of 5-formyl-aminosailcylate-inulin: A potential prodrug of 5-aminosalicylic acid

Many carbohydrate polymers that have been used as carriers for colon-targeted drugs have shown benefits against colonic diseases. The objectives of this project were to (1) synthesize a derivative of 5-aminosalicylic acid (5-ASA), a drug used to treat inflammatory bowel disease, containing inulin, a carbohydrate polymer that has shown benefits against inflammatory bowel disease; (2) quantify the release of 5-ASA from the conjugate during in vitro digestion and fermentation; and (3) determine the in vitro fermentation properties of the conjugated inulin. Inulin was esterified with 5-formyl-aminosalicylic acid (5-fASA), a derivative of 5-ASA, with a degree of substitution of 0.185±0.014. During in vitro digestion and fermentation, 56.2±6.5% of 5-fASA was released in 24 h. Gut bacteria did not deformylate 5-fASA to 5-ASA as anticipated. Though conjugation of inulin with 5-fASA reduced bifidogenicity at 24 h compared with native inulin (8.26±0.03 log cfu/g versus 8.59±0.09 log cfu/g, respectively, p<0.01), conjugated 5-fASA-inulin showed protracted fermentation with higher short chain fatty acid (SCFA) and equivalent butyrate concentration at 24 h (9.02±0.68 μmol SCFA/mg carbohydrate versus 7.54±0.53 μmol SCFA/mg carbohydrate, p<0.01; 2.16±0.22 μmol butyrate/mg carbohydrate versus 2.34±0.17 μmol butyrate/mg carbohydrate, respectively, p=0.09). These data suggest that conjugation of inulin with 5-fASA may support SCFA and especially butyrate-producing bacteria through inulin fermentation in the distal colon, an important site of inflammation, together with delivery of 5-fASA. However, gut bacteria were unable to hydrolyze the formyl group from 5-fASA; thus alternative strategies to conjugate 5-ASA to inulin or remove the formyl group from 5-fASA are needed.

Release kinetics of 5-aminosalicylic acid from halloysite

This paper investigates desorption of 5-aminosalicilyc acid (5-ASA) adsorbed onto halloysite (HL). Desorption isotherms were fitted according to kinetic laws obtained considering release of 5-ASA from HL as the phase of desorption of the previously adsorbed drug molecules both inside the nanotubes of HL as onto the surface of clay particles and/or in the inter-particle spaces of their aggregates [28]. Desorption isotherms has been also fitted with other equations frequently used in drug release kinetics studies. The best fitting corresponded to the kinetic model proposed; in agreement with the results of adsorption [28].

Preparation and characterization of OSA/CS core–shell microgel: in vitro drug release and degradation properties

Cationic polymers have been widely used as drug delivery systems. Herein, an oxidized sodium alginate/chitosan (OSA/CS) core–shell microgel was prepared via water-in-oil emulsion method. Morphological properties of the resulting microgel were determined by transmission electron microscopy, hydrodynamic diameter of the microgel was characterized by dynamic light scattering. The objective of this work was to achieve the colon-specific delivery of an antiulcerative colitis drug using a fully nontoxic carrier. 5-aminosalicylic acid (5-ASA) was chosen as a model drug, which is rapidly absorbed before entering the colon, thus it is necessary to develop a colon-specific delivery system for it. The in vitro drug release profile was established in buffer solutions with 0.1 M HCl/NaCl (pH 1.2) and 0.1 M phosphate buffered saline (pH 7.4) at 37 °C. The results indicated that this OSA/CS core–shell microgel inhibited the release of 5-ASA in stomach to a certain extent and is degradable in physiological conditions. Due to the excellent biocompatible nature of CS and OSA, this core–shell microgel has good biocompatibility and may have potential applications in oral controlled drug delivery systems.

Controlled release of 5-aminosalicylicacid from chitosan based pH and temperature sensitive hydrogels

A series of temperature and pH responsive hydrogels based on chitosan and poly(N-isopropyl acrylamide) (PNIPA) was prepared by redox polymerization. Effect of the composition on swelling behavior of the hydrogels and the release of 5-aminosaylcilic acid (5-ASA) at different temperatures and pHs have been investigated. Ammonium persulphate and TEMED were used as a redox pair at room temperature. As a cross linker, methacrylated chitosan was synthesized through the reaction of chitosan with glycidyl methacrylate (GMA). Introduction of the cross-linker provided the hydrogels with pH and temperature sensitivities. The phase transition temperatures of the hydrogels were determined by derivative differential scanning calorimeter (DDSC). Their phase transition temperatures were increased by chitosan content. Swelling behaviors and the release of 5-ASA varied significantly with pH, temperature and the gel composition. The release of 5-ASA from the hydrogels was followed by UV–Vis and fluorescence spectroscopy.

Synthesis and in vitro kinetic study of novel mutual azo prodrug for inflammatory bowel disease

Background: Inflammatory bowel disease (IBD) refers to idiopathic inflammatory diseases of the intestine, principally ulcerative colitis and Crohn’s disease. IBD is characterized by chronic inflammation in the mucosal membrane of large intestine. 5ASA is the gold standard for the treatment of IBD and when searched for a better 5ASA prodrug, a novel mutual azo prodrug was designed and synthesized. Methods: A mutual prodrug was synthesized by coupling p-phenetidine with salicylic acid. The stability of this prodrug in HCl buffer, in phosphate buffer and in rat fecal matter were monitored. Results: The chemical structure of mutual prodrug was characterized by physical and spectroscopic techniques using FTIR, UV/Visible, 1 H-NMR and 13 C-NMR spectra. In vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-ASA and p-phenetidine, whereas in phosphate buffer (pH 7.4) only (22.04 %) release was observed over a period of (6 hr.). In rat fecal matter, the hydrolysis of mutual prodrug was almost complete (77.96 %), with a half-life of 182.67 min, following zero order kinetics. Conclusion: The mutual prodrug was split in colon by the action of bacterial azoreductase into 5-ASA and p-phenetidine that constitute two anti-inflammatory compounds with different mechanisms of action. Therefore, this mutual prodrug is a promising colon specific prodrug for IBD and worthy of further study.

Synthesis of pro-prodrugs l-lysine based for 5-aminosalicylic acid and 6-mercaptopurine colon specific release

The aim of this work is to design, prepare and characterize l-lysine based prodrugs capable of targeting 6-mercaptopurine to the colon, an anti-tumor and immunosuppressant drug, and 5-aminosalicylic acid (5-ASA), drug of choice for inflammatory bowel disease (IBD). More specifically, Nɛ-feruloyl-S-(6-purinyl)- l-lysine and Nɛ-acryloyl-S-(6-purinyl)- l-lysine were synthesized and then characterized by FT-IR, 1H-NMR and GC/MS spectroscopies. The ability of feruloyl derivative in inhibiting lipid peroxidation in rat liver microsomal membranes, induced in vitro by tert-butyl hydroperoxide as source of free radicals, was evaluated. Moreover, Nɛ-acryloyl-S-(6-purinyl)- l-lysine, polymerizable prodrug, was used to microspheres realization for 5-ASA release. These lasts, obtained by emulsion inverse technique, were characterized by light scattering and scanning electron microscopy (SEM) analysis. The microspheres equilibrium swelling degree was evaluated and showed good swelling behaviour in simulating colonic fluids. Results confirm the possibility that the application range of l-lysine prodrug can be extended to the treatment of intestinal diseases whose conventional therapy envisages medications with serious side effects that, thanks to this new strategy, can be minimized in an optimal way.

Structure and colon-targeted releasing property of resistant octenyl succinate starch

Granular and crystalline structures of resistant octenyl succinic anhydride (OSA) modified corn starch were characterized using scanning electron microscopy (SEM), optical microscopy and X-ray diffraction. As a colon-targeted delivery carrier, the releasing property of resistant OSA-modified starch was also investigated by In-vitro model. Enhanced succinylation of starch considerably increased the enzyme and acid resistibility to digestion, indicating the improvement of starch colon-targeting property as the degree of substitution (DS) increased. From In-vitro releasing assay, the resistant OSA-modified corn starch based matrix tablets could deliver bioactive components to the colon when the RS content and hydrophobicity were suitable. The relationship between the structure and In-vitro release properties of resistant OSA-modified corn starch suggests that an optimal DS and crystalline:amorphous ratio can be responsible for 5-ASA release. The matrix tablets used resistant OSA-modified corn starch with moderate DS (0.60) and V-type crystal morphology co-exist with the amorphous structure as carrier show good colon-targeted releasing properties.

Concentration Dependence of 5-Aminosalicylic Acid Pharmacological Actions in Intestinal Mucosa after Oral Administration of a pH-Dependent Formulation

Asacol, a medication that delivers delayed release 5-aminosalicylic acid (5-ASA), is a useful therapeutic agent for inflammatory bowel disease (IBD), but the relationship between its pharmacological actions and intestinal concentrations has not been studied in detail. Therefore, our aim was to assess 5-ASA's pharmacological actions as a function of its concentration at its target site. We first evaluated 5-ASA's release profiles in vitro by the paddle method and found that Asacol starts to release 5-ASA at pH ≥ 7. Orally administered Asacol pharmacokinetic parameters were evaluated in dogs. Asacol's T(max) was much longer than that of the time-dependent release 5-ASA formulation. We also determined 5-ASA's distribution in the intestinal mucosa and found that it is effectively delivered there by Asacol. These results indicated that Asacol released 5-ASA in a pH-dependent manner, resulting in efficient delivery to the large intestine. We also compared the mucosal 5-ASA concentrations with the IC(50) values for scavenging free radicals or suppressing LTB(4) production. The 5-ASA concentration in the large intestine was higher than IC(50) values necessary to suppress inflammatory processes. We also report the release characteristics of Asacol and the targeted delivery of 5-ASA to affected sites in IBD patients.