Simulated Comparison of Topical and Oral Formulations of 5-Aminosalicylate for the Treatment of Ulcerative Colitis

Stobaugh, Derrick J.; Deepak, Parakkal; Thorpe, Matthew; Hannon, Bruce; Ehrenpreis, Eli D.

doi:10.1002/ibd.23003

Cited by 3 publications

(2 citation statements)

References 33 publications

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“…and colon. [27][28][29] The summary pharmacokinetic parameters (AUC 0-24 and C max ) for 5-ASA with Asacol are broadly similar to those previously reported.…”

Section: Safetysupporting

confidence: 81%

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Similar pharmacokinetics of three dosing regimens comprising two oral delayed‐release mesalamine formulations in healthy adult volunteers: Randomised, open‐label, parallel‐group study

Casteele

Jakate

McNamee

et al. 2020

Brit J Clinical Pharma

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Mesalamine is the first-line therapy for treating mild-to-moderate ulcerative colitis. Multiple mesalamine formulations are available, with similar safety and efficacy profiles. Mesalamine is commonly administered as divided dosing, although once-daily dosing may provide benefits for patients. We evaluated the pharmacokinetics of three dosing regimens of two oral delayed-release mesalamine formulations in healthy adult volunteers. Methods: A randomised, open-label, parallel-group study of mesalamine pharmacokinetics following Lialda 2 × 1.2 g once daily (QD) (dose A), Asacol 6 × 400 mg QD (dose B), or Asacol 2 × 400 mg three times daily (TID) (dose C) over 7 days. Assessments included 5-aminosalicylic acid (5-ASA) and N-acetyl 5-aminosalicylic acid (N-Ac-5-ASA, primary metabolite) pharmacokinetics (A e (%), AUC 0-24 and C max), safety and tolerability. Results: All enrolled volunteers (n = 37) completed the study. Steady state was achieved for all treatments by day 4. Ratios (95% CI) of means for steady-state AUC 0-24 (dose A vs B 90.3% [39.8, 204.8], dose A vs C 123.5% [55.3, 275.7], dose B vs C 136.8% [61.3, 305.5]) and C max (dose A vs B 106.0% [46.4, 242.2], dose A vs C 133.0% [59.1, 299.0], dose B vs C 125.5% [55.8, 282.1]) were similar for all 5-ASA treatments. Mean urinary excretion of 5-ASA plus N-Ac-5-ASA was comparable between treatments (dose A 21.3%, dose B 20.2%, dose C 17.9%). All treatment regimens were well tolerated; no safety issues were observed. Conclusions: Plasma and urine pharmacokinetics for Asacol TID, Asacol QD, and Lialda QD are similar, suggesting similar daily systemic exposures can be obtained with either TID or QD dosing. NCT00751699.

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“…and colon. [27][28][29] The summary pharmacokinetic parameters (AUC 0-24 and C max ) for 5-ASA with Asacol are broadly similar to those previously reported.…”

Section: Safetysupporting

confidence: 81%

“…Dose A and dose B had similar plasma 5‐ASA and N‐Ac‐5‐ASA concentration‐time profiles and urinary excretion data. Additionally, Asacol and Lialda are both designed to release mesalamine in the same region of the gastrointestinal tract, namely the terminal ileum and colon 27–29 …”

Section: Discussionmentioning

confidence: 99%

Similar pharmacokinetics of three dosing regimens comprising two oral delayed‐release mesalamine formulations in healthy adult volunteers: Randomised, open‐label, parallel‐group study

Casteele

Jakate

McNamee

et al. 2020

Brit J Clinical Pharma

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Efficacy of topical versus oral 5-aminosalicylate for treatment of 2,4,6-trinitrobenzene sulfonic acid-induced ulcerative colitis in rats

Chen

Cao

Wang

et al. 2014

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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5-aminosalicylic acid (5-ASA) is drug of choice for the treatment of ulcerative colitis (UC). In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC. A total of 60 rats were divided into sham operation group (receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube), model group, topical 5-ASA group, oral Etiasa group (a release agent of mesalazine used as positive control) and oral 5-ASA group (n=12 each). Different treatments were administered 1 day after UC induction. The normal saline (2 mL) was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group (7.5 g/L, twice per day, 100 mg/kg), and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa (7.5 g/L, twice per day, 100 mg/kg) and 5-ASA (7.5 g/L, twice per day, 100 mg/kg), respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography (HPLC). The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.

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Apprehending Ulcerative Colitis Management With Springing Up Therapeutic Approaches: Can Nanotechnology Play a Nascent Role?

et al. 2021

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Simulated Comparison of Topical and Oral Formulations of 5-Aminosalicylate for the Treatment of Ulcerative Colitis

Cited by 3 publications

References 33 publications

Similar pharmacokinetics of three dosing regimens comprising two oral delayed‐release mesalamine formulations in healthy adult volunteers: Randomised, open‐label, parallel‐group study

Similar pharmacokinetics of three dosing regimens comprising two oral delayed‐release mesalamine formulations in healthy adult volunteers: Randomised, open‐label, parallel‐group study

Efficacy of topical versus oral 5-aminosalicylate for treatment of 2,4,6-trinitrobenzene sulfonic acid-induced ulcerative colitis in rats

Apprehending Ulcerative Colitis Management With Springing Up Therapeutic Approaches: Can Nanotechnology Play a Nascent Role?

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