Influence of Pharmaceutical Formulation on the Mucosal Concentration of 5-Aminosalicylic Acid and &lt;i&gt;N&lt;/i&gt;-Acetylmesalamine in Japanese Patients with Ulcerative Colitis

Yamamoto, Yuki; Masuda, Satohiro; Nakase, Hiroshi; Matsuura, Minoru; Maruyama, Shihoko; Hisamatsu, Tadakazu; Suzuki, Yasuo; Matsubara, Kazuo

doi:10.1248/bpb.b18-00561

Cited by 10 publications

(8 citation statements)

References 20 publications

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“…5‐ASA concentrations in both the sigmoid colon and the rectum were comparable among patients who received different 5‐ASA formulations. However, 5‐ASA concentrations tended to be lower in patients receiving time‐dependent 5‐ASA than patients receiving pH‐dependent 5‐ASA or multimatrix system 5‐ASA, and this was consistent with the results of previous studies 20,21 . In Japan, the manufacturer's maximum dose of time‐dependent, pH‐dependent, or multimatrix system 5‐ASA is 4.0, 3.6, and 4.8 g, respectively.…”

Section: Discussionsupporting

confidence: 89%

Mucosal concentrations of N‐acetyl‐5‐aminosalicylic acid related to endoscopic activity in ulcerative colitis patients with mesalamine

Fukuda

Takabayashi

Hagihara

et al. 2020

J of Gastro and Hepatol

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Background and Aim 5‐Aminosalicylic acid (5‐ASA) is a fundamental treatment for mild‐to‐moderate ulcerative colitis (UC). 5‐ASA is taken up into the colonic mucosa and metabolized to N‐acetyl‐5‐ASA (Ac‐5‐ASA). Few studies have assessed whether mucosal 5‐ASA and Ac‐5‐ASA concentrations are associated with endoscopic remission. This study aimed to investigate differences in 5‐ASA and Ac‐5‐ASA concentrations according to endoscopic activity. Methods This single‐center, prospective, cross‐sectional study was conducted between March 2018 and February 2019. UC patients who were administered with 5‐ASA medication for at least 8 weeks before sigmoidoscopy were enrolled. Mucosal 5‐ASA and Ac‐5‐ASA concentrations were measured using liquid chromatography with tandem mass spectrometry. The primary endpoint was defined as the difference in mucosal concentrations of 5‐ASA and Ac‐5‐ASA, according to the Mayo endoscopic subscore (MES). Results Mucosal concentrations were analyzed in 50 patients. In the sigmoid colon, the median 5‐ASA concentration in patients with MES of 0 (17.3 ng/mg) was significantly higher than MES ≥ 1 (6.4 ng/mg) (P = 0.019). The median 5‐ASA concentrations in patients with Ulcerative Colitis Endoscopic Index of Severity ≤ 1 (16.4 ng/mg) were also significantly higher than in patients with Ulcerative Colitis Endoscopic Index of Severity ≥ 2 (4.63 ng/mg) (P = 0.047). In the sigmoid colon, the concentration of Ac‐5‐ASA was higher in patients with MES of 0 (21.2 ng/mg) than in patients with MES ≥ 1 (5.81 ng/mg) (P = 0.022). Conclusions The present study showed that mucosal Ac‐5‐ASA concentrations, as well as 5‐ASA concentrations, are higher in UC patients with endoscopic remission. Ac‐5‐ASA may be useful for a biomarker of 5‐ASA efficacy.

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Section: Discussionsupporting

confidence: 89%

Mucosal concentrations of N‐acetyl‐5‐aminosalicylic acid related to endoscopic activity in ulcerative colitis patients with mesalamine

Fukuda

Takabayashi

Hagihara

et al. 2020

J of Gastro and Hepatol

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“…5-ASA concentrations were lower in patients using Pentasa than in patients using Asacol. 10 , 18 , 27 A recent study found that 5-ASA concentrations in the mucosa of the left hemicolon and rectum were higher in users of Mezavant and high 5-ASA concentrations were associated with a beneficial mucosal bacterial composition. 4 Furthermore, the mucosal 5-ASA concentration is correlated inversely to the degree of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with the persistence of oral 5-aminosalicylic acid monotherapy in ulcerative colitis: a nationwide Norwegian cohort study

Fossmark

Olaisen

Martinsen

et al. 2021

Therap Adv Gastroenterol

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Background: Oral 5-aminosalicylic acid (5-ASA) is the mainstay treatment of ulcerative colitis (UC) and therapy with oral 5-ASA is associated with beneficial outcomes. We have examined factors associated with the persistence of oral 5-ASA treatment in a national cohort of UC patients. Methods: Patients with newly diagnosed UC from 2010 to 2014 using oral 5-ASA monotherapy were identified by combining data from the Norwegian Patient Registry and the Norwegian Prescription Database. The median follow-up time was 1029 days. Drug persistence was defined as duration of oral 5-ASA preparation as monotherapy. Non-persistence of a oral 5-ASA preparation as monotherapy was defined as stopping oral 5-ASA, initiation of any further anti-inflammatory treatment including a course of glucocorticoids and a change to another oral 5-ASA preparation. Drug persistence was analyzed using the Kaplan–Meier method and influence of covariates on drug persistence was analyzed with the Cox proportional hazard model. Results: A total of 3421 patients were identified. The overall median 5-ASA drug persistence was 179 days. In univariate analyses, persistence was associated with preparation type and high-dose treatment, while oral glucocorticoid use or hospitalization around the start of oral 5-ASA were associated with shorter 5-ASA persistence. In multivariate analyses, oral glucocorticoids [HR 1.67 (1.54–1.80), p < 0.005] and hospitalization around start of 5-ASA [HR 1.23 (1.14–1.34), p < 0.005] were associated with non-persistence, whereas high dose (⩾3 g/day) 5-ASA was associated with longer persistence [HR 0.68 (0.65–0.71), p < 0.005]. Conclusion: High-dose treatment with oral 5-ASA was associated with longer persistence of oral 5-ASA monotherapy, whereas the presence of factors indicating more severe disease around initiation of 5-ASA monotherapy was associated with a shorter persistence.

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“…Conventionally, 5-aminosalicylic acid (5-ASA or mesalazine), steroids, calcineurin inhibitors, etc., have been used to treat ulcerative colitis (UC) [ 1 , 2 ]. However, in recent years, numerous biological products have been developed, and treatment options for UC are expanding [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

CYP3A5 Genotype as a Potential Pharmacodynamic Biomarker for Tacrolimus Therapy in Ulcerative Colitis in Japanese Patients

Yamamoto

Nakase

Matsuura

et al. 2020

IJMS

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Tacrolimus has been used to induce remission in patients with steroid-refractory ulcerative colitis. It poses a problem of large individual differences in dosage necessary to attain target blood concentration and, often, this leads to drug inefficacy. We examined the difference in mRNA expression levels of ATP binding cassette transporter B1 (ABCB1) between inflamed and non-inflamed tissues, and the influence of CYP3A5 genotype on tacrolimus therapy. The mRNA expression of CYP3A4 in colonic mucosa and that of cytochrome p450 3A5 (CYP3A5) and ABCB1 in inflamed and non-inflamed areas were examined in 14 subjects. The mRNA expression levels of CYP3A5 were higher than that of CYP3A4. The mRNA expression of ABCB1 was lower in the inflamed than in the non-inflamed mucosa, despite that of CYP3A5 mRNA level being not significantly changed. Hence, the deterioration of the disease is related to the reduction of the barrier in the inflamed mucosa. The relationship between CYP3A5 genotype and blood concentration, dose, and concentration/dose (C/D) ratio of tacrolimus in 15 subjects was studied. The tacrolimus dose to maintain equivalent blood concentrations was lower in CYP3A5*3/*3 than in CYP3A5*1 carriers, and the C/D ratio was significantly higher in the latter. Thus, CYP3A5 polymorphism information played a role in determining the initial dose of tacrolimus. Furthermore, since the effect of tacrolimus appears earlier in CYP3A5*3/*3 than in CYP3A5*1/*1 and *1/*3, it seems necessary to change the evaluation time of therapeutic effect by CYP3A5 genotype. Additionally, the relationship between CYP3A5 genotype and C/D ratio of tacrolimus in colonic mucosa was investigated in 10 subjects. Tacrolimus concentration in the mucosa was two-fold higher in CYP3A5*3/*3 than in CYP3A5*1 carriers, although no significant difference in tacrolimus-blood levels was observed. Therefore, the local concentration of tacrolimus affected by CYP3A5 polymorphism might be related to its therapeutic effect.

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Influence of Pharmaceutical Formulation on the Mucosal Concentration of 5-Aminosalicylic Acid and <i>N</i>-Acetylmesalamine in Japanese Patients with Ulcerative Colitis

Cited by 10 publications

References 20 publications

Mucosal concentrations of N‐acetyl‐5‐aminosalicylic acid related to endoscopic activity in ulcerative colitis patients with mesalamine

Mucosal concentrations of N‐acetyl‐5‐aminosalicylic acid related to endoscopic activity in ulcerative colitis patients with mesalamine

Factors associated with the persistence of oral 5-aminosalicylic acid monotherapy in ulcerative colitis: a nationwide Norwegian cohort study

CYP3A5 Genotype as a Potential Pharmacodynamic Biomarker for Tacrolimus Therapy in Ulcerative Colitis in Japanese Patients

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