5-Aminosalicylic Acid in a Slow-Release Preparation: Bioavailability, Plasma Level, and Excretion in Humans

Rasmussen, Sten Nørby; Bondesen, S; Hvidberg, Eigill F.; Hansen, Steen Honoré; Binder, Vibeke; Halskov, S.; Flachs, Helga

doi:10.1016/s0016-5085(82)80075-9

Cited by 216 publications

(38 citation statements)

References 20 publications

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“…However, later s t u d i e~~~r~~ have found pH levels which are in agreement with the results of the present study. One of the reasons for the differences between the earlier results and our results probably is that the stability of the capsules and batteries has been improved, which have increased the lifespan of a capsule from [3][4][5][6] h to 2000 h. The rise in pH down the small intestine is most likely to be caused by an excretion of bicarbonate into the lumen of the gut," and an absorption of organic acids from the intestinal contents.…”

Section: Discussioncontrasting

confidence: 65%

pH‐Profile and regional transit times of the normal gut measured by a radiotelemetry device

Fallingborg

Christensen

Ingeman-Nielsen

et al. 1989

Aliment Pharmacol Ther

213

147

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The pH of the gut lumen was measured in 39 healthy persons using a pH-sensitive, radiotransmitting capsule. Thirteen persons were studied twice. The location of the capsule was determined by X-ray. The pH rose from 6.4 in the duodenum to 7.3 in the distal part of the small intestine. In 17 persons the pH dropped by 0.1-0.8 pH units during the last hours of the small intestinal transit. The pH was 5.7 in the caecum, but rose to 6.6 in the rectum. Gastric residence time was 1.1 h, small intestinal transit was 8 h, and colonic transit time was 17.5 h (median values). The results provide a firmer basis for prediction of the level, and the rate of release of active substance from pH-dependent sustainedrelease oral preparations. I N T R O D U C T I O NThe biological availability of a tablet is influenced by a variety of factors including regional intestinal pH and regional intestinal transit times. These factors are of particular importance for the effect of some newly developed sustained-release 5-aminosalicylic acid preparations designed for the treatment of chronic inflam-Correspondence to :

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Section: Discussioncontrasting

confidence: 65%

pH‐Profile and regional transit times of the normal gut measured by a radiotelemetry device

Fallingborg

Christensen

Ingeman-Nielsen

et al. 1989

Aliment Pharmacol Ther

213

147

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“…Our model suggests that an increase in frequency of bowel movements, a decrease in the normal colonic transit rate, or some combination may be responsible for the reported difference in drug distributions in the colon. Many studies have only used healthy subjects to determine the pharmacokinetics of orally dosed 5‐ASA; 9, 10, 26–37 however, clear differences in gastrointestinal motility probably limit the generalizability of these data to patients with ulcerative colitis.…”

Section: Discussionmentioning

confidence: 99%

A dynamic model of colonic concentrations of delayed‐release 5‐aminosalicylic acid (Asacol)

Thorpe

Ehrenpreis

Putt

et al. 2009

Aliment Pharmacol Ther

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SUMMARYBackround 5-ASA in a pH sensitive tablet (Asacol) is administered as three doses ⁄ day to treat ulcerative colitis. Once daily dosing may improve patient adherence. Simulation of colonic levels of 5-ASA can be used to compare dosing regimens. AimTo create a dynamic model of colonic concentrations of delayed-release 5-aminosalicylic acid (Asacol). MethodsUsing published data, we created a computer model with STELLA software to simulate amounts of colonic 5-ASA in the total colon, right, transverse, descending and sigmoid ⁄ rectum after daily and three time ⁄ day Asacol. ResultsThe model predicted similar total and regional amounts of 5-ASA with both regimens. Distribution of 5-ASA was 38% in the right colon, 33% in the transverse colon and 14% each in the descending and sigmoid ⁄ rectal colon. Simulated increases in colonic motility and defecation rate exaggerated this 5-ASA distribution, resulting in negligible amounts of 5-ASA in the sigmoid ⁄ rectal region. ConclusionsThis computer model suggests that Asacol can be administered as a single daily dose. The model supports experimental and clinical observations that alternate dose or route of administration may be necessary to achieve adequate 5-ASA amounts in the distal colon during acute exacerbations of ulcerative colitis. This simulation cannot account for all sources of variability in the clinical setting, but provides a rationale for further investigation.

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“…The filtrate was stored at -20' C. The second portion was mixed with phosphate buffer 0.1 M, pH = 6.0. At this pH 5-ASA release from granules is minimal (Rasmussen et al, 1982).…”

Section: Analytical Proceduresmentioning

confidence: 90%

“…Under normal gastrointestinal transit granules in the tablets in a pH dependent manner. conditions up to 90% of SASP is split in the Both the kinetic profile and the release pattern Correspondence: Professor E. F. Hvidberg, Department of Clinical Pharmaology 3124,Rigshospitalet,9 Blegdamsvej, DK-2100 Copenhagen 0, Denmark 365 366 Lisbet A. Christensen et al of this preparation have been extensively studied (Rasmussen et al, 1982). The aim of the present study was to investigate the influence of the intestinal transit time on the release of 5-ASA from Pentasa.…”

Section: Introductionmentioning

confidence: 98%

Release of 5‐aminosalicylic acid from Pentasa during normal and accelerated intestinal transit time.

Christensen

Slot

Sánchez

et al. 1987

Brit J Clinical Pharma

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The influence of intestinal transit time on the release of 5‐ aminosalicylic acid (5‐ASA) from a peroral, slow‐release preparation (Pentasa) was studied at steady state in seven healthy volunteers. Daily dose was 1500 mg Pentasa, normal transit time (NTT) was 24 h (16‐ 26 h) and accelerated transit time (ATT), caused by a laxative, was 5 h (4‐9 h). Median total recovery (24 h, 5‐ASA + acetyl‐5‐ASA) was 87% (61‐ 129%) (NTT) and 81% (56‐100%) (ATT), respectively, (P greater than 0.10). The total faecal excretion of 5‐ASA (per cent of dose) increased from 16%, (9‐21%) (NTT) to 29%, (16‐38%) (ATT) (P less than 0.02). Free 5‐ASA rose from 12% (4‐19%) to 17% (10‐25%), the retained part (in granules) from 4% (2‐5%) to 12% (4‐24%). Urinary excretion decreased correspondingly from 32% (19‐59%) to 21% (11‐38%), predominantly as Ac‐ 5‐ASA (P less than 0.05). Mean plasma Ac‐5‐ASA concentration decreased from 1.42 micrograms ml‐1 to 0.86 microgram ml‐1 (P less than 0.05). An almost complete release of 5‐ASA from Pentasa takes place during NTT. At ATT conditions about 88% is released, indicating Pentasa to be an acceptable source of 5‐ASA in diarrhoeal states.

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5-Aminosalicylic Acid in a Slow-Release Preparation: Bioavailability, Plasma Level, and Excretion in Humans

Cited by 216 publications

References 20 publications

pH‐Profile and regional transit times of the normal gut measured by a radiotelemetry device

pH‐Profile and regional transit times of the normal gut measured by a radiotelemetry device

A dynamic model of colonic concentrations of delayed‐release 5‐aminosalicylic acid (Asacol)

Release of 5‐aminosalicylic acid from Pentasa during normal and accelerated intestinal transit time.

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