Identification of oxidation products of 5-aminosalicylic acid in faeces and the study of their formation invitro

Jensen, Joan; Cornett, Claus; Olsen, Carl Erik; Bondesen, S; Christensen, John D.; Christensen, Lisbet Ambrosius; Tjørnelund, Jette; Hansen, Steen Honoré

doi:10.1016/0006-2952(93)90271-w

Cited by 14 publications

(8 citation statements)

References 22 publications

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“…5‐ASA is acetylated by colonic epithelial cells 27 and after oral administration in humans, comparable levels of 5‐ASA and N‐acetyl 5‐ASA levels are found in the urine, plasma and faeces, as well as the intestinal lumen 16 , . 28 Studies to‐date on the use of N‐acetyl‐5‐ASA (N‐acetyl‐5‐aminosalicylic acid) in the treatment of patients with active colitis are conflicting, 29 possibly as a result of the relatively poor uptake of N‐acetyl‐5‐ASA by the colonic epithelium in comparison to 5‐ASA 30 . In the present studies, N‐acetyl 5‐ASA demonstrated antioxidant activity in cell‐free systems, but only at a high concentration.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell‐free systems and inflamed human colorectal biopsies

Simmonds

Millar

Blake³

et al. 1999

Aliment Pharmacol Ther

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Section: Discussionmentioning

confidence: 99%

Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell‐free systems and inflamed human colorectal biopsies

Simmonds

Millar

Blake³

et al. 1999

Aliment Pharmacol Ther

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“…Following the first stool passage, 400 ml methanol was added to the container and the mixture was stirred vigorously for adequate contact and immediate denaturisation of bacteria stopping transformation of drug. In non-prepared faeces, N-acetylation and azo-reduction by faecal bacteria may take place, whereas in niethanol-prepared faeces all metabolic transformation stops (58). 24 h methanol-denatured faeces was weighed, homogenized and a sample stored at minus 18 degrees C for further analysis (Hansen).…”

Section: V2 Methods Of the Present Studiesmentioning

confidence: 99%

Intestinal Fate of 5‐aminosalicylic Acid: Regional and Systemic Kinetic Studies in Relation to Inflammatory Bowel Disease

Bondesen¹

1997

Pharmacology & Toxicology

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“…An explanation might be that`fresh' stool (`10 h between defecation and insertion) contains more binding places for mesalazine or allows further metabolism into unidenti®ed metabolites (Jensen et al 1993) or more faecal water and more distribution over the stool mass than more compact and older stool ( b 10 h). With the older and compact stool, the suppository mass with mesalazine may be spread along the rectum wall, enhancing the absorption.…”

Section: Metabolism and Renal Excretionmentioning

confidence: 99%

Mono- and Biphasic Plasma Concentration-time Curves of Mesalazine from a 500 mg Suppository in Healthy Male Volunteers Controlled by the Time of Defecation before Dosing

Vree

Dammers²,

Exler

et al. 2000

Journal of Pharmacy and Pharmacology

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This study was based on data from a bioequivalence study (n=24) of two different formulations of suppositories containing 500 mg mesalazine (formulation I and II), with a similar dissolution profile in phosphate buffer pH 6.8. There was a large intra- and intersubject variability in the plasma concentration-time curves of mesalazine from both suppositories. The aim of the investigation was to identify the parameters that caused the observed large variations in release and absorption of mesalazine in the rectum. Plasma mesalazine and acetylmesalazine, and urine acetylmesalazine concentrations were determined according to validated methods involving HPLC analysis with coulometric detection. Lower limit of quantitation values were respectively 10.4 and 19.4 ng mL(-1) in plasma and 0.96 microg mL(-1) in urine. The time of defecation before and after insertion was recorded. There was a clear distinction between subjects who showed monophasic mesalazine release/absorption and those who showed biphasic and more extended release/absorption. With formulation I there was a correlation between time of defecation before dosing and the type of absorption, monophasic and biphasic absorbers showed a significant difference in the time of defecation, e.g. 9.7+/-5.6 h vs 18.8+/-11.9 h (P = 0.0218). The impact of time of defecation before dosing was non-significant with formulation II, 16.7+/-7.2 h vs 15.1+/-4.2 h (P = 0.67). The impact of the time elapsed between administration and time of defecation after the insertion of the suppository was not significant for the type of release/absorption. The plasma concentration-time curves of the metabolite ran parallel to that of the parent drug, the more parent drug was released/absorbed, the more was acetylated (P = 0.0013) and excreted into the urine (P = 0.0004). After absorption the compound was metabolized into acetylmesalazine, and renally excreted (12-13% of the dose). Monophasic release/ absorption resulted in 7.1% metabolite with I and 10.3% with II (P = 0.0004), while biphasic release/absorption gave 16.8% metabolite with I and 15.5% with II. The renal clearance of the metabolite acetylmesalazine was independent of the observed defecation patterns (300 mL min(-1), P > 0.8), stool composition, and type of absorption.

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Identification of oxidation products of 5-aminosalicylic acid in faeces and the study of their formation invitro

Cited by 14 publications

References 22 publications

Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell‐free systems and inflamed human colorectal biopsies

Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell‐free systems and inflamed human colorectal biopsies

Intestinal Fate of 5‐aminosalicylic Acid: Regional and Systemic Kinetic Studies in Relation to Inflammatory Bowel Disease

Mono- and Biphasic Plasma Concentration-time Curves of Mesalazine from a 500 mg Suppository in Healthy Male Volunteers Controlled by the Time of Defecation before Dosing

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