Absorption of Oral Mesalazine-Containing Preparations and the Influence of Famotidine on the Absorption

Wiltink, E. H. H.; Mulder, Cjj; Stolk, L. M. L.; Rietbroek, Ron C.; Verbeek, Cornelis; Tytgat, G. N. J.

doi:10.3109/00365529009095533

Cited by 10 publications

(6 citation statements)

References 15 publications

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“…However, Wiltink et al studied the effect of famotidine as an H2-antagonist on the absorption of different mesalamine formulations (Asacol, Salofalk, and Pentasa) based on the acetylmesalazine assay in the urine and finally the authors unexpectedly observed lower absorption of Asacol in combination with famotidine. 24 However, pantoprazole may be more effective than omeprazole in UC patients, because of its higher bioavailability and more plasma elimination half-life (hours). 25 Pharmacodynamic studies of omeprazole have shown an increasing trend toward reactivity with some drugs.…”

Section: Discussionmentioning

confidence: 99%

<p>Protective Effect of Asacol in Combination with Pantoprazole in Ulcerative Colitis Patients Who Defecate Asacol Tablets Intactly: A Clinical Trial Study</p>

Bashiri¹,

Bozorgomid²

2020

CEG

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Purpose: Mesalazine formulations are the drug of choice in the treatment of ulcerative colitis (UC). They are released at alkaline pH in order to deliver 5-aminosalicylic acid to the colon. The colonic pH is significantly lower in UC patients than in normal patients. This study was conducted for the first time to evaluate the clinical efficacy of co-administration of pantoprazole and Asacol in the treatment of ulcerative colitis patients who excrete intact Asacol tablets in the feces. Patients and Methods: Thirty patients with mild-to-moderate active ulcerative colitis who reported passing intact Asacol tablets in stools received oral Asacol plus pantoprazole for 2 weeks. The demographic characteristics of the patients and the body mass index were collected through interviews. For each patient, the stool frequency, visible blood, and presence of intact Asacol tablets in the stool were compared before and pantoprazole treatment. Results: There was a significant difference in the stool frequency (number of daily stools) before and after pantoprazole treatment (mean ± sd, 6.06 ± 1.04 vs 1.5± 0.5; P<0.001). In addition, pantoprazole administration statistically reduced visible blood in the stool (100%; P<0.001). Co-administration of pantoprazole and Asacol was effective in all age groups and both sexes. None of the patients reported the presence of intact Asacol tablets in their stools. Conclusions: Co-administration of pantoprazole and Asacol would be useful for symptom management UC patients that excrete intact Asacol tablets in their feces through increasing the gastric pH and releasing the maximum concentration of the drug in the proximal gastrointestinal tract.

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Section: Discussionmentioning

confidence: 99%

<p>Protective Effect of Asacol in Combination with Pantoprazole in Ulcerative Colitis Patients Who Defecate Asacol Tablets Intactly: A Clinical Trial Study</p>

Bashiri¹,

Bozorgomid²

2020

CEG

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“…In Pentasa® tablets mesalazine is located in microgranules surrounded by ethyl-cellulose. In a previous study Wiltink et al (1990) compared the urinary excretion of acetyl-mesalazine after ingestion of 3 different pH-dependent, sustained release mesalazine preparations (including Pentasa®) with and without cqncomitant ingestion of famotidine (another H2-receptor blocking agent) and found that famotidine had no effect on the absorption of mesalazine from Pentasa® tablets. Our study demonstrates that cimetidine 400mg twice daily increases the median pH of the stomach by about 1.3 units, but does not significantly affect the pH of other parts of the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

Concomitant Administration of Cimetidine and Pentasa®

et al. 1992

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The effect of cimetidine on gastrointestinal pH and on the bioavailability of mesalazine from Pentasa® tablets was investigated in 12 healthy volunteers. Each subject received Pentasa® 2g daily for I week, with and without concomitant administration of cimetidine '400mg twice daily in a randomised crossover study. The pH profile of the gastrointestinal tract was determined using a radiotransmitting, pH-sensitive capsule. The median gastric pH was increased to 3.1 when cimetidine was administered with Pentasa® compared with 1.8 when Pentasa® was taken alone. There was no significant change in the pH of the small intestine and colon during the 2 regimens. Concentrations of mesalazine and acetyl-mesalazine were determined from urine and faeces samples collected over the last 48 hours of each crossover period. Concomitant administration of cimetidine did not affect the faecal water concentration of mesalazine, nor the urinary excretion of dru~.In conclusion, ingestion of cimetidine 800 mgjday does not change the gastrointestinal pH sufficiently to affect the bioavailability of mesalazine from Pentasa®. It is therefore unlikely that concomitant ingestion of cimetidine with Pentasa® will affect the therapeutic efficacy of the latter.

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“…There are several differently formulated oral formulations of mesalazine available, and dosage recommendations vary (Martindale 1996). Some 20 to 50% of an oral dose was absorbed after oral administration to healthy volunteers (Hardy et al 1987;Meyers et al 1987;Wiltink et al 1990). Absorption from rectal dosage forms also varied widely, and was reported to depend on the dose, the formulation, and the pH, but mean absorption of around 10±20% of the rectal dose has been reported (Brogden & Sorkin 1989;Norlander et al 1989).…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested that the metabolite, acetylmesalazine, may itself have some activity, but this remains in doubt (Fischer et al 1983). The acetylated metabolite is excreted mainly in the urine by ®ltration and active tubular secretion, together with traces of the parent compound (`1%) (Brogden & Sorkin 1989;Meyers et al 1987;Wiltink et al 1990). Peak plasma drug levels following rectal administration are very low and highly variable (Norlander et al 1989;Jacobsen et al 1991).…”

Section: Introductionmentioning

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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Absorption of Oral Mesalazine-Containing Preparations and the Influence of Famotidine on the Absorption

Cited by 10 publications

References 15 publications

<p>Protective Effect of Asacol in Combination with Pantoprazole in Ulcerative Colitis Patients Who Defecate Asacol Tablets Intactly: A Clinical Trial Study</p>

<p>Protective Effect of Asacol in Combination with Pantoprazole in Ulcerative Colitis Patients Who Defecate Asacol Tablets Intactly: A Clinical Trial Study</p>

Concomitant Administration of Cimetidine and Pentasa®

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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