Pharmacokinetics of 5-aminosalicylic acid from controlled-release capsules in man

Yu, Dale K.; Morrill, Bruce; Eichmeier, Larry S.; Giesing, Dennis H.; Weir, Scott J.; Lanman, Robert C.; Lanman, M. B.

doi:10.1007/bf00198311

Cited by 15 publications

(11 citation statements)

References 9 publications

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“…Biphasic absorption of mesalazine, as reported in this study, was also shown by Bondesen et al (1991) and Yu et al (1995) after oral administration.…”

Section: Discussionsupporting

confidence: 87%

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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“…Biphasic absorption of mesalazine, as reported in this study, was also shown by Bondesen et al (1991) and Yu et al (1995) after oral administration.…”

Section: Discussionsupporting

confidence: 87%

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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“…Taking into account the difference of dosage with our study (250 mg once daily vs 2 g bid), after the oral administration of 2 g, Bondesen et al would have had to obtain a mean C max of 735.07 ng/mL to agree with our data. Similarly, Yu et al, 34 after a single oral administration of 1 g ethylcellulose‐coated mesalazine to healthy volunteers, reported a mean t max of 3.5 hours and a mean C max of 995.41 ng/mL (mathematically corresponding to 1990.82 ng/mL after 2 g). For the metabolite N‐acetyl‐5‐ASA, after a single oral administration of 250 mg of 5‐ASA (ethylcellulose‐coated mesalazine), Hardy et al 21 reported a mean lag time of 0.72 hours, a mean t max of 4.3 hours, and a mean C max of 380 ng/mL (mathematically corresponding to 3040 ng/mL for a dosage of 2 g) in healthy volunteers.…”

Section: Discussionmentioning

confidence: 84%

Is Once‐Daily Mesalazine Equivalent to the Currently Used Twice‐Daily Regimen? A Study Performed in 30 Healthy Volunteers

Gandia

Idier

Houin

2007

The Journal of Clinical Pharma

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A randomized, 2-way, crossover study was conducted in 30 volunteers to compare the pharmacokinetic profile of a new once-daily dosing regimen of mesalazine (1 x 4 g/d) with the current twice-daily dosage (2 x 2 g/d) used in many European countries. The 2 dosages were administrated orally for 8 days, separated by a 2-week washout. Plasma concentrations of mesalazine and N-acetyl-mesalazine were determined on days 1 and 8 by a validated high-performance liquid chromatography method and C(max), t(max), and AUCs calculated. The bioequivalence was obtained for a 90% confidence interval of the AUC(0-24h) ratio (test/reference) for mesalazine and N-acetyl-mesalazine on days 1 and 8, within the range of 0.80 to 1.25. The bioequivalence was demonstrated on day 1 for mesalazine and N-acetyl-mesalazine and on day 8 for mesalazine. As it is desirable to offer patients a preparation with a less frequent administration to enhance compliance, this once-daily regimen may be an attractive dosing option.

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“…3c) of all multiple dose studies. The single dose studies (or study parts) analysed only HS and their results were comparable with multiple dose studies [12,30,31,39,42,43,[52][53][54].…”

Section: Dose and Formulationmentioning

confidence: 91%

“…Figure 1 depicts the search results: 26 of 532 records were eligible. By snowballing we identified another 13 eligible studies [12,[30][31][32][33][34][35][36][37][38][39][40][41]. The 39 included studies (n = 939) included 3 conference abstracts [42][43][44].…”

Section: Data Extraction and Assessment Of Biasmentioning

confidence: 99%

Does the 5-Aminosalicylate Concentration Correlate with the Efficacy of Oral 5-Aminosalicylate and Predict Response in Patients with Inflammatory Bowel Disease? A Systematic Review

et al. 2019

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Background: Oral 5-aminosalicylic acid (5-ASA, mesalazine) is the first choice therapeutic agent for treating mild-tomoderate ulcerative colitis (UC). Unfortunately a significant group of patients fail to respond. Therapeutic drug monitoring might help to maintain or induce remission by providing a tool for optimization of 5-ASA therapy. However, plasma and urine concentrations of 5-ASA reflect systemic uptake and are not useful to evaluate therapeutic effect. Objectives: To explore if mucosal and faecal 5-ASA values correlate with disease activity and/or therapeutic effects in patients with inflammatory bowel disease, especially UC. Method: We identified studies that analysed 5-ASA in faeces or mucosa of humans using an oral 5-ASA formulation, using PubMed and Embase. Results: In total, 39 studies (n = 939) were included, 27 on faecal 5-ASA, 9 on mucosal concentrations, and 3 on both faecal and mucosal values. We included 33 cross-sectional studies, 3 randomised clinical trials, 2 longitudinal cohorts and 1 randomized cross-over study. Mucosal 5-ASA concentrations in healthy subjects and patients on equivalent doses of 5-ASA were not found to differ remarkably. In the sub-analysis of mucosal 5-ASA concentrations in patients with active or quiescent UC, a higher concentration was seen during remission. Faecal concentrations were associated with 5-ASA doses but not with disease activity. Differences in faecal or mucosal 5-ASA values could not be ascribed to different 5-ASA formulations. Conclusions: An increase of the mucosal 5-ASA concentrations was observed during remission in patients with UC. No clear relationship between the faecal 5-ASA excretion and the therapeutic efficacy was identified.

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Pharmacokinetics of 5-aminosalicylic acid from controlled-release capsules in man

Cited by 15 publications

References 9 publications

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

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

Is Once‐Daily Mesalazine Equivalent to the Currently Used Twice‐Daily Regimen? A Study Performed in 30 Healthy Volunteers

Does the 5-Aminosalicylate Concentration Correlate with the Efficacy of Oral 5-Aminosalicylate and Predict Response in Patients with Inflammatory Bowel Disease? A Systematic Review

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